• Nano-Micro Letters
  • Vol. 16, Issue 1, 268 (2024)
Qingdong Bao1,3,4,†, Xiaoting Zhang2,†, Zhankun Hao4, Qinghua Li1,3,4..., Fan Wu4, Kaiyuan Wang5, Yang Li2,*, Wenlong Li1,3,4,** and Hua Gao1,3,4,***|Show fewer author(s)
Author Affiliations
  • 1State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao 266071, People’s Republic of China
  • 2State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, People’s Republic of China
  • 3Eye Hospital of Shandong First Medical University, Jinan, 250021, People’s Republic of China
  • 4College of Ophthalmology, Shandong First Medical University, Jinan 250000, People’s Republic of China
  • 5Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore 119074, Singapore
  • show less
    DOI: 10.1007/s40820-024-01477-3 Cite this Article
    Qingdong Bao, Xiaoting Zhang, Zhankun Hao, Qinghua Li, Fan Wu, Kaiyuan Wang, Yang Li, Wenlong Li, Hua Gao. Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases[J]. Nano-Micro Letters, 2024, 16(1): 268 Copy Citation Text show less
    References

    [1] J. Li, R. Ge, K. Lin, J. Wang, Y. He et al., Advances in the application of microneedles in the treatment of local organ diseases. Small 20, 2306222 (2024).

    [2] L.K. Vora, A.H. Sabri, P.E. McKenna, A. Himawan, A.R.J. Hutton et al., Microneedle-based biosensing. Nat. Rev. Bioeng. 2, 64–81 (2024).

    [3] K. Glover, D. Mishra, S. Gade, L.K. Vora, Y. Wu et al., Microneedles for advanced ocular drug delivery. Adv. Drug Deliv. Rev. 201, 115082 (2023).

    [4] M. Zheng, T. Sheng, J. Yu, Z. Gu, C. Xu, Microneedle biomedical devices. Nat. Rev. Bioeng. 2, 324–342 (2023).

    [5] Y.N. Ertas, D. Ertas, A. Erdem, F. Segujja, S. Dulchavsky et al., Diagnostic, therapeutic, and theranostic multifunctional microneedles. Small (2024).

    [6] H. Chopra, Priyanka, O.P. Choudhary, T.B. Emran, Microneedles for ophthalmic drug delivery: recent developments. Int. J. Surg. 109, 551–552 (2023).

    [7] X. Tang, J. Liu, R. Yan, Q. Peng, Carbohydrate polymer-based bioadhesive formulations and their potentials for the treatment of ocular diseases: a review. Int. J. Biol. Macromol. 242, 124902 (2023).

    [8] T. Moniz, S.A. Costa Lima, S. Reis, Marine polymeric microneedles for transdermal drug delivery. Carbohyd. Polym. 266, 118098 (2021).

    [9] F. Damiri, N. Kommineni, S.O. Ebhodaghe, R. Bulusu, V. Jyothi et al., Microneedle-based natural polysaccharide for drug delivery systems (DDS): progress and challenges. Pharmaceuticals 15, 190 (2022).

    [10] R. Day, Polysaccharides in ocular tissue*. Am. J. Ophthalmol. 33, 224–226 (1950).

    [11] S. Dou, Q. Wang, B. Zhang, C. Wei, H. Wang et al., Single-cell atlas of keratoconus corneas revealed aberrant transcriptional signatures and implicated mechanical stretch as a trigger for keratoconus pathogenesis. Cell Discov. 8, 66 (2022).

    [12] A.S. Monzel, M. Levin, M. Picard, The energetics of cellular life transitions. Life Metab. 3, load051 (2024).

    [13] N.S. Chandra, S. Gorantla, S. Priya, G. Singhvi, Insight on updates in polysaccharides for ocular drug delivery. Carbohyd. Polym. 297, 120014 (2022).

    [14] J. Pushpamalar, P. Meganathan, H.L. Tan, N.A. Dahlan, L.-T. Ooi et al., Development of a polysaccharide-based hydrogel drug delivery system (DDS): an update. Gels 7, 153 (2021).

    [15] R.A. Armstrong, R.P. Cubbidge, Chapter 1 - the eye and vision: an overview, in Handbook of Nutrition, Diet and the Eye. ed. by V.R. Preedy (Academic Press, San Diego, 2014), pp.3–9

    [16] 1-eye: anatomy, physiology and barriers to drug delivery, in Ocular Transporters and Receptors. ed. by K. Cholkar, S.R. Dasari, D. Pal, and A.K. Mitra (Woodhead Publishing, 2013), pp.1–36

    [17] C.E. Willoughby, D. Ponzin, S. Ferrari, A. Lobo, K. Landau et al., Anatomy and physiology of the human eye: effects of mucopolysaccharidoses disease on structure and function—a review. Clin. Exp. Ophthalmol. 38, 2–11 (2010).

    [18] B. Chakrabarti, J.W. Park, E.S. Stevens, Glycosaminoglycans: structure and interactio. Crit. Rev. Biochem. Mol. Biol. 8, 225–313 (1980).

    [19] M. Zako, M. Yoneda, Chapter 8-functional glycosaminoglycans in the eye, in Carbohydrate Chemistry, Biology and Medical Applications. ed. by H.G. Garg, M.K. Cowman, C.A. Hales (Elsevier, Oxford, 2008), pp.181–208

    [20] S. Puri, Y.M. Coulson-Thomas, T.F. Gesteira, V.J. Coulson-Thomas, Distribution and function of glycosaminoglycans and proteoglycans in the development, homeostasis and pathology of the ocular surface. Front. Cell Dev. Biol. 8, 731 (2020).

    [21] C.T. Mörner, Untersuchung der proteїnsubstanzen in den leichtbrechenden medien des auges i. Biol. Chem. 18, 61–106 (1894).

    [22] K. Meyer, J.W. Palmer, The polysaccharide of the vitreous humor. J. Biol. Chem. 107, 629–634 (1934).

    [23] X. Lin, T. Mekonnen, S. Verma, C. Zevallos-Delgado, M. Singh et al., Hyaluronan modulates the biomechanical properties of the cornea. Invest. Ophthalmol. Vis. Sci. 63, 6 (2022).

    [24] L. Zhan-feng, S. Han-wen, Progress of the research on chemically modifications of polysaccharide. J Hebei Univ (Nat Sci Ed) 25, 104 (2005).

    [25] L. Huang, M. Shen, G.A. Morris, J. Xie, Sulfated polysaccharides: immunomodulation and signaling mechanisms. Trends Food Sci. Technol. 92, 1–11 (2019).

    [26] M. Inatani, H. Tanihara, Proteoglycans in retina. Prog. Retin. Eye Res. 21, 429–447 (2002).

    [27] K.L. Segars, V. Trinkaus-Randall, Glycosaminoglycans: Roles in wound healing, formation of corneal constructs and synthetic corneas. Ocul. Surf. 30, 85–91 (2023).

    [28] E.A. Balazs, G. Armand, Glycosaminoglycans and proteoglycans of ocular tissues, in Glycosaminoglycans and Proteoglycans in Physiological and Pathological Processes of Body Systems. ed. by R.V.R.S. Varma, S. Karger (Karger Publishers, Switzerland, 1982), pp.480–499

    [29] A. Tawara, H.H. Varner, J.G. Hollyfield, Distribution and characterization of sulfated proteoglycans in the human trabecular tissue. Invest. Ophthalmol. Vis. Sci. 30, 2215–2231 (1989). PMID: 2793361.

    [30] D.M. Snow, M. Watanabe, P.C. Letourneau, J. Silver, A chondroitin sulfate proteoglycan may influence the direction of retinal ganglion cell outgrowth. Development 113, 1473–1485 (1991).

    [31] Z. Zhuola, S. Barrett, Y.A. Kharaz, R. Akhtar, Nanostructural and mechanical changes in the sclera following proteoglycan depletion. Model. Artif. Intell. Ophthalmol. 2, 14–17 (2018).

    [32] J.A. Rada, V.R. Achen, S. Penugonda, R.W. Schmidt, B.A. Mount, Proteoglycan composition in the human sclera during growth and aging. Invest. Ophthalmol. Vis. Sci. 41, 1639–1648 (2000). PMID: 10845580.

    [33] J.A. Summers, The sclera and its role in regulation of the refractive state, in Pathologic Myopia. ed. by R.F. Spaide, K. Ohno-Matsui, L.A. Yannuzzi (Springer, Cham, 2021), pp.87–104.

    [34] J.A. Rada, V.R. Achen, C.A. Perry, P.W. Fox, Proteoglycans in the human sclera. Evidence for the presence of aggrecan. Invest. Ophthalmol. Vis. Sci. 38, 1740–1751 (1997). PMID: 9286262.

    [35] N. Jabeen, M. Atif, Polysaccharides based biopolymers for biomedical applications: a review. Polym. Adv. Technol. 35, e6203 (2024).

    [36] Y. Yu, M. Shen, Q. Song, J. Xie, Biological activities and pharmaceutical applications of polysaccharide from natural resources: a review. Carbohyd. Polym. 183, 91–101 (2018).

    [37] M. Kenchegowda, U. Hani, A. Al Fatease, N. Haider, K. Ramesh et al., Tiny titans-unravelling the potential of polysaccharides and proteins based dissolving microneedles in drug delivery and theranostics: a comprehensive review. Int. J. Biol. Macromol. 253, 127172 (2023).

    [38] D.F.S. Fonseca, C. Vilela, A.J.D. Silvestre, C.S.R. Freire, A compendium of current developments on polysaccharide and protein-based microneedles. Int. J. Biol. Macromol. 136, 704–728 (2019).

    [39] R.S. Bhadale, V.Y. Londhe, A systematic review of carbohydrate-based microneedles: current status and future prospects. J. Mater. Sci. Mater. Med. 32, 89 (2021).

    [40] A.I. Barbosa, F. Serrasqueiro, T. Moniz, S.A. Costa Lima, S. Reis, Marine polysaccharides for skin drug delivery: hydrogels and microneedle solutions, in Marine Biomaterials: Drug Delivery and Therapeutic Applications. ed. by S. Jana, S. Jana (Springer Nature Singapore, Singapore, 2022), pp.209–250

    [41] P. Snetkov, K. Zakharova, S. Morozkina, R. Olekhnovich, M. Uspenskaya, Hyaluronic acid: the influence of molecular weight on structural, physical, physico-chemical, and degradable properties of biopolymer. Polymers 12, 1800 (2020).

    [42] I. Saha, V.K. Rai, Hyaluronic acid based microneedle array: recent applications in drug delivery and cosmetology. Carbohyd. Polym. 267, 118168 (2021).

    [43] H. Kang, Z. Zuo, R. Lin, M. Yao, Y. Han et al., The most promising microneedle device: present and future of hyaluronic acid microneedle patch. Drug Deliv. 29, 3087–3110 (2022).

    [44] H. Shi, S. Huai, H. Wei, Y. Xu, L. Lei et al., Dissolvable hybrid microneedle patch for efficient delivery of curcumin to reduce intraocular inflammation. Int. J. Pharm. 643, 123205 (2023).

    [45] Y. Jiang, Y. Jin, C. Feng, Y. Wu, W. Zhang et al., Engineering hyaluronic acid microneedles loaded with Mn2+ and temozolomide for topical precision therapy of melanoma. Adv. Healthc. Mater. 13, e2303215 (2023).

    [46] J.H. Tay, Y.H. Lim, M. Zheng, Y. Zhao, W.S. Tan et al., Development of hyaluronic acid-silica composites via in situ precipitation for improved penetration efficiency in fast-dissolving microneedle systems. Acta Biomater. 172, 175–187 (2023).

    [47] Y. Wu, L.K. Vora, R.F. Donnelly, T.R.R. Singh, Rapidly dissolving bilayer microneedles enabling minimally invasive and efficient protein delivery to the posterior segment of the eye. Drug Deliv. Transl. Res. 13, 2142–2158 (2023).

    [48] G. Bonfante, H. Lee, L. Bao, J. Park, N. Takama et al., Comparison of polymers to enhance mechanical properties of microneedles for bio-medical applications. Micro Nano Syst. Lett. 8, 1–13 (2020).

    [49] S. Zhang, L. Yang, S. Hong, J. Liu, J. Cheng et al., Collagen type I–loaded methacrylamide hyaluronic acid hydrogel microneedles alleviate stress urinary incontinence in mice: a novel treatment and prevention strategy. Colloids Surf. B Biointerfaces 222, 113085 (2023).

    [50] A. Than, C. Liu, H. Chang, P.K. Duong, C.M.G. Cheung et al., Self-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug delivery. Nat. Commun. 9, 4433 (2018).

    [51] S. Baek, K.P. Lee, C.S. Han, S.H. Kwon, S.J. Lee, Hyaluronic acid-based biodegradable microneedles loaded with epidermal growth factor for treatment of diabetic foot. Macromol. Res. 32, 13–22 (2024).

    [52] B. Wang, W. Zhang, Q. Pan, J. Tao, S. Li et al., Hyaluronic acid-based CuS nanoenzyme biodegradable microneedles for treating deep cutaneous fungal infection without drug resistance. Nano Lett. 23, 1327–1336 (2023).

    [53] Y. Yu, Y. Gao, Y. Zeng, W. Ge, C. Tang et al., Multifunctional hyaluronic acid/gelatin methacryloyl core-shell microneedle for comprehensively treating oral mucosal ulcers. Int. J. Biol. Macromol. 266, 131221 (2024).

    [54] S.M. Whitcup, M.R. Robinson, Development of a dexamethasone intravitreal implant for the treatment of noninfectious posterior segment uveitis. Ann. N. Y. Acad. Sci. 1358, 1–12 (2015).

    [55] P. Suriyaamporn, P. Opanasopit, T. Ngawhirunpat, W. Rangsimawong, Computer-aided rational design for optimally Gantrez® S-97 and hyaluronic acid-based dissolving microneedles as a potential ocular delivery system. J. Drug Deliv. Sci. Technol. 61, 102319 (2021).

    [56] H. Shi, J. Zhou, Y. Wang, Y. Zhu, D. Lin et al., A rapid corneal healing microneedle for efficient ocular drug delivery. Small 18, 2104657 (2022).

    [57] S. Juhng, J. Song, J. You, J. Park, H. Yang et al., Fabrication of liraglutide-encapsulated triple layer hyaluronic acid microneedles (TLMs) for the treatment of obesity. Lab Chip 23, 2378–2388 (2023).

    [58] Y. Li, J. Lin, P. Wang, F. Zhu, M. Wu et al., Tumor microenvironment-responsive yolk–shell NaCl@virus-inspired tetrasulfide-organosilica for ion-interference therapy via osmolarity surge and oxidative stress amplification. ACS Nano 16, 7380–7397 (2022).

    [59] Y. Shi, M. Yu, K. Qiu, T. Kong, C. Guo et al., Immuno-modulation of tumor and tumor draining lymph nodes through enhanced immunogenic chemotherapy by nano-complexed hyaluronic acid/polyvinyl alcohol microneedle. Carbohyd. Polym. 325, 121491 (2024).

    [60] Y. Li, J. Lin, P. Wang, Q. Luo, H. Lin et al., Tumor microenvironment responsive shape-reversal self-targeting virus-inspired nanodrug for imaging-guided near-infrared-II photothermal chemotherapy. ACS Nano 13, 12912–12928 (2019).

    [61] J. Yang, Z. Chu, Y. Jiang, W. Zheng, J. Sun et al., Multifunctional hyaluronic acid microneedle patch embedded by cerium/zinc-based composites for accelerating diabetes wound healing. Adv. Healthc. Mater. 12, 2300725 (2023).

    [62] S. Liu, Q. Bai, Y. Jiang, Y. Gao, Z. Chen et al., Multienzyme-like nanozyme encapsulated ocular microneedles for keratitis treatment. Small 20, 2308403 (2024).

    [63] M. Liang, L. Shang, Y. Yu, Y. Jiang, Q. Bai et al., Ultrasound activatable microneedles for bilaterally augmented sono-chemodynamic and sonothermal antibacterial therapy. Acta Biomater. 158, 811–826 (2023).

    [64] S. Shi, Y. Jiang, Y. Yu, M. Liang, Q. Bai et al., Piezo-augmented and photocatalytic nanozyme integrated microneedles for antibacterial and anti-inflammatory combination therapy. Adv. Funct. Mater. 33, 2210850 (2023).

    [65] N. Dabholkar, S. Gorantla, T. Waghule, V.K. Rapalli, A. Kothuru et al., Biodegradable microneedles fabricated with carbohydrates and proteins: revolutionary approach for transdermal drug delivery. Int. J. Biol. Macromol. 170, 602–621 (2021).

    [66] W. Du, X. Li, M. Zhang, G. Ling, P. Zhang, Investigation of the antibacterial properties of hyaluronic acid microneedles based on chitosan and MoS2. J. Mater. Chem. B 11, 7169–7181 (2023).

    [67] A. Chandrasekharan, Y.J. Hwang, K.Y. Seong, S. Park, S. Kim et al., Acid-treated water-soluble chitosan suitable for microneedle-assisted intracutaneous drug delivery. Pharmaceutics 11, 209 (2019).

    [68] Y. Yang, S. Wang, Y. Wang, X. Wang, Q. Wang et al., Advances in self-assembled chitosan nanomaterials for drug delivery. Biotechnol. Adv. 32, 1301–1316 (2014).

    [69] D.A. Castilla-Casadiego, K.A. Miranda-Muñoz, J.L. Roberts, A.D. Crowell, D. Gonzalez-Nino et al., Biodegradable microneedle patch for delivery of meloxicam for managing pain in cattle. PLoS ONE 17, e0272169 (2022).

    [70] A. Zamboulis, S. Nanaki, G. Michailidou, I. Koumentakou, M. Lazaridou et al., Chitosan and its derivatives for ocular delivery formulations: recent advances and developments. Polymers 12, 1519 (2020).

    [71] M.-C. Chen, M.-H. Ling, K.-Y. Lai, E. Pramudityo, Chitosan microneedle patches for sustained transdermal delivery of macromolecules. Biomacromol 13, 4022–4031 (2012).

    [72] C. Ryall, S. Chen, S. Duarah, J. Wen, Chitosan-based microneedle arrays for dermal delivery of Centella asiatica. Int. J. Pharm. 627, 122221 (2022).

    [73] D.A. Castilla-Casadiego, H. Carlton, D. Gonzalez-Nino, K.A. Miranda-Muñoz, R. Daneshpour et al., Design, characterization, and modeling of a chitosan microneedle patch for transdermal delivery of meloxicam as a pain management strategy for use in cattle. Mater. Sci. Eng. C 118, 111544 (2021).

    [74] P. Suriyaamporn, P. Opanasopit, W. Rangsimawong, T. Ngawhirunpat, Optimal design of novel microemulsions-based two-layered dissolving microneedles for delivering fluconazole in treatment of fungal eye infection. Pharmaceutics 14, 472 (2022).

    [75] S. Manna, R.K. Banerjee, J.J. Augsburger, M.F. Al-Rjoub, A. Donnell et al., Biodegradable chitosan and polylactic acid-based intraocular micro-implant for sustained release of methotrexate into vitreous: analysis of pharmacokinetics and toxicity in rabbit eyes. Graefes Arch. Clin. Exp. Ophthalmol. 253, 1297–1305 (2015).

    [76] L. Popa, M.V. Ghica, C.E. Dinu-Pîrvu, T. Irimia, Chitosan: A good candidate for sustained release ocular drug delivery systems, in Chitin-Chitosan—Myriad Functionalities in Science and Technology. (InTech, London, UK, 2018), pp.283–310.

    [77] W. Li, E.S. Thian, M. Wang, Z. Wang, L. Ren, Surface design for antibacterial materials: from fundamentals to advanced strategies. Adv. Sci. 8, 2100368 (2021).

    [78] W. Li, H. Chen, J. Cai, M. Wang, X. Zhou et al., Poly (pentahydropyrimidine)-based hybrid hydrogel with synergistic antibacterial and pro-angiogenic ability for the therapy of diabetic foot ulcers. Adv. Funct. Mater. 33, 2303147 (2023).

    [79] W. Li, J. Cai, W. Zhou, X. Zhao, M. Wang et al., Poly (aspartic acid)-based self-healing hydrogel with precise antibacterial ability for rapid infected-wound repairing. Colloids Surf. B Biointerfaces 221, 112982 (2023).

    [80] J. Chi, X. Zhang, C. Chen, C. Shao, Y. Zhao et al., Antibacterial and angiogenic chitosan microneedle array patch for promoting wound healing. Bioact. Mater. 5, 253–259 (2020).

    [81] S.R. Pardeshi, M.P. More, C.V. Pardeshi, P.J. Chaudhari, A.D. Gholap et al., Novel crosslinked nanoparticles of chitosan oligosaccharide and dextran sulfate for ocular administration of dorzolamide against glaucoma. J. Drug Deliv. Sci. Technol. 86, 104719 (2023).

    [82] A. Kumari, P.K. Sharma, V.K. Garg, G. Garg, Ocular inserts—advancement in therapy of eye diseases. J. Adv. Pharm. Technol. Res. 1, 291–296 (2010).

    [83] R. Yuan, N. Yang, Y. Huang, W. Li, Y. Zeng et al., Layer-by-layer microneedle-mediated rhEGF transdermal delivery for enhanced wound epidermal regeneration and angiogenesis. ACS Appl. Mater. Interfaces 15, 21929–21940 (2023).

    [84] Z. Chen, Y. Zhang, K. Feng, T. Hu, B. Huang et al., Facile fabrication of quaternized chitosan-incorporated biomolecular patches for non-compressive haemostasis and wound healing. Fundam. Res. (2023).

    [85] H. Wei, S. Liu, Z. Tong, T. Chen, M. Yang et al., Hydrogel-based microneedles of chitosan derivatives for drug delivery. React. Funct. Polym. 172, 105200 (2022).

    [86] E. Díaz-Montes, Dextran: sources, structures, and properties. Polysaccharides 2, 554–565 (2021).

    [87] S. Huang, H. Liu, S. Huang, T. Fu, W. Xue et al., Dextran methacrylate hydrogel microneedles loaded with doxorubicin and trametinib for continuous transdermal administration of melanoma. Carbohyd. Polym. 246, 116650 (2020).

    [88] J. Liang, Y. Yu, C. Li, Q. Li, P. Chen et al., Tofacitinib combined with melanocyte protector α-MSH to treat vitiligo through dextran based hydrogel microneedles. Carbohyd. Polym. 305, 120549 (2023).

    [89] S. Fakhraei Lahiji, Y. Jang, I. Huh, H. Yang, M. Jang et al., Exendin-4–encapsulated dissolving microneedle arrays for efficient treatment of type 2 diabetes. Sci. Rep. 8, 1170 (2018).

    [90] J. Leelawattanachai, K. Panyasu, K. Prasertsom, S. Manakasettharn, H. Duangdaw et al., Highly stable and fast-dissolving ascorbic acid-loaded microneedles. Int. J. Cosmet. Sci. 45, 612–626 (2023).

    [91] H. Liu, B. Wang, M. Xing, F. Meng, S. Zhang et al., Thermal stability of exenatide encapsulated in stratified dissolving microneedles during storage. Int. J. Pharm. 636, 122863 (2023).

    [92] A.S. Bernd, M. Aihara, J.D. Lindsey, R.N. Weinreb, Influence of molecular weight on intracameral dextran movement to the posterior segment of the mouse eye. Invest. Ophthalmol. Vis. Sci. 45, 480–484 (2004).

    [93] J.-S. Yang, Y.-J. Xie, W. He, Research progress on chemical modification of alginate: a review. Carbohyd. Polym. 84, 33–39 (2011).

    [94] X. Mei, Y. Chang, J. Shen, Y. Zhang, C. Xue, Expression and characterization of a novel alginate-binding protein: a promising tool for investigating alginate. Carbohyd. Polym. 246, 116645 (2020).

    [95] D. Al Sulaiman, J.Y. Chang, N.R. Bennett, H. Topouzi, C.A. Higgins et al., Hydrogel-coated microneedle arrays for minimally invasive sampling and sensing of specific circulating nucleic acids from skin interstitial fluid. ACS Nano 13, 9620–9628 (2019).

    [96] C.V. Liew, L.W. Chan, A.L. Ching, P.W.S. Heng, Evaluation of sodium alginate as drug release modifier in matrix tablets. Int. J. Pharm. 309, 25–37 (2006).

    [97] P. Agulhon, M. Robitzer, L. David, F. Quignard, Structural regime identification in ionotropic alginate gels: influence of the cation nature and alginate structure. Biomacromol 13, 215–220 (2012).

    [98] Y. Zhang, G. Jiang, W. Yu, D. Liu, B. Xu, Microneedles fabricated from alginate and maltose for transdermal delivery of insulin on diabetic rats. Mater. Sci. Eng. C 85, 18–26 (2018).

    [99] Y.K. Demir, Z. Akan, O. Kerimoglu, Sodium alginate microneedle arrays mediate the transdermal delivery of bovine serum albumin. PLoS ONE 8, e63819 (2013).

    [100] T. Tiraton, O. Suwantong, P. Chuysinuan, P. Ekabutr, P. Niamlang et al., Biodegradable microneedle fabricated from sodium alginate-gelatin for transdermal delivery of clindamycin. Mater. Today Commun. 32, 104158 (2022).

    [101] Z. Zhou, M. Xing, S. Zhang, G. Yang, Y. Gao, Process optimization of Ca2+ cross-linked alginate-based swellable microneedles for enhanced transdermal permeability: more applicable to acidic drugs. Int. J. Pharm. 618, 121669 (2022).

    [102] W. Yu, G. Jiang, Y. Zhang, D. Liu, B. Xu et al., Polymer microneedles fabricated from alginate and hyaluronate for transdermal delivery of insulin. Mater. Sci. Eng. C 80, 187–196 (2017).

    [103] R. Jia, C. Cui, L. Gao, Y. Qin, N. Ji et al., A review of starch swelling behavior: its mechanism, determination methods, influencing factors, and influence on food quality. Carbohyd. Polym. 321, 121260 (2023).

    [104] Y. Zhang, M. Wu, D. Tan, Q. Liu, R. Xia et al., A dissolving and glucose-responsive insulin-releasing microneedle patch for type 1 diabetes therapy. J. Mater. Chem. B 9, 648–657 (2021).

    [105] R.S. Singh, N. Kaur, V. Rana, J.F. Kennedy, Pullulan: a novel molecule for biomedical applications. Carbohyd. Polym. 171, 102–121 (2017).

    [106] S. Tiwari, R. Patil, S.K. Dubey, P. Bahadur, Derivatization approaches and applications of pullulan. Adv. Colloid Interfaces Sci. 269, 296–308 (2019).

    [107] R.S. Singh, N. Kaur, M. Hassan, J.F. Kennedy, Pullulan in biomedical research and development-a review. Int. J. Biol. Macromol. 166, 694–706 (2021).

    [108] L.K. Vora, A.J. Courtenay, I.A. Tekko, E. Larrañeta, R.F. Donnelly, Pullulan-based dissolving microneedle arrays for enhanced transdermal delivery of small and large biomolecules. Int. J. Biol. Macromol. 146, 290–298 (2020).

    [109] R.S. Singh, N. Kaur, D. Singh, S.S. Purewal, J.F. Kennedy, Pullulan in pharmaceutical and cosmeceutical formulations: a review. Int. J. Biol. Macromol. 231, 123353 (2023).

    [110] D.F.S. Fonseca, P.C. Costa, I.F. Almeida, P. Dias-Pereira, I. Correia-Sá et al., Pullulan microneedle patches for the efficient transdermal administration of insulin envisioning diabetes treatment. Carbohyd. Polym. 241, 116314 (2020).

    [111] W. Cheng, Y. Zhu, G. Jiang, K. Cao, S. Zeng et al., Sustainable cellulose and its derivatives for promising biomedical applications. Prog. Mater. Sci. 138, 101152 (2023).

    [112] A.C.Q. Silva, B. Pereira, N.S. Lameirinhas, P.C. Costa, I.F. Almeida et al., Dissolvable carboxymethylcellulose microneedles for noninvasive and rapid administration of diclofenac sodium. Macromol. Biosci. 23, 2200323 (2023).

    [113] A.A. Seetharam, H. Choudhry, M.A. Bakhrebah, W.H. Abdulaal, M.S. Gupta et al., Microneedles drug delivery systems for treatment of cancer: a recent update. Pharmaceutics 12, 1101 (2020).

    [114] T. Aziz, A. Farid, F. Haq, M. Kiran, A. Ullah et al., A review on the modification of cellulose and its applications. Polymers 14, 3206 (2022).

    [115] J.-Y. Kim, M.-R. Han, Y.-H. Kim, S.-W. Shin, S.-Y. Nam et al., Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer’s disease. Eur. J. Pharm. Biopharm. 105, 148–155 (2016).

    [116] X. Lan, W. Zhu, X. Huang, Y. Yu, H. Xiao et al., Microneedles loaded with anti-PD-1–cisplatin nanoparticles for synergistic cancer immuno-chemotherapy. Nanoscale 12, 18885–18898 (2020).

    [117] J.W. Lee, S.-O. Choi, E.I. Felner, M.R. Prausnitz, Dissolving microneedle patch for transdermal delivery of human growth hormone. Small 7, 531–539 (2011).

    [118] Y.-H. Park, S.K. Ha, I. Choi, K.S. Kim, J. Park et al., Fabrication of degradable carboxymethyl cellulose (CMC) microneedle with laser writing and replica molding process for enhancement of transdermal drug delivery. Biotechnol. Bioeng. 21, 110–118 (2016).

    [119] N. Qiang, Z. Liu, M. Lu, Y. Yang, F. Liao et al., Preparation and properties of polyvinylpyrrolidone/sodium carboxymethyl cellulose soluble microneedles. Materials 16, 3417 (2023).

    [120] R. Sharma, K. Kuche, P. Thakor, V. Bhavana, S. Srivastava et al., Chondroitin sulfate: emerging biomaterial for biopharmaceutical purpose and tissue engineering. Carbohyd. Polym. 286, 119305 (2022).

    [121] J. Yu, Y. Xia, H. Zhang, X. Pu, T. Gong et al., A semi-interpenetrating network-based microneedle for rapid local anesthesia. J. Drug Deliv. Sci. Technol. 78, 103984 (2022).

    [122] M.M. Abdallah, N. Fernández, A.A. Matias, M. de Rosário Bronze, Hyaluronic acid and chondroitin sulfate from marine and terrestrial sources: extraction and purification methods. Carbohyd. Polym. 243, 116441 (2020).

    [123] S. Liu, S. Zhang, Y. Duan, Y. Niu, H. Gu et al., Transcutaneous immunization of recombinant staphylococcal enterotoxin B protein using a dissolving microneedle provides potent protection against lethal enterotoxin challenge. Vaccine 37, 3810–3819 (2019).

    [124] K. Fukushima, A. Ise, H. Morita, R. Hasegawa, Y. Ito et al., Two-layered dissolving microneedles for percutaneous delivery of peptide/protein drugs in rats. Pharm. Res. 28, 7–21 (2011).

    [125] D. Poirier, F. Renaud, V. Dewar, L. Strodiot, F. Wauters et al., Hepatitis B surface antigen incorporated in dissolvable microneedle array patch is antigenic and thermostable. Biomaterials 145, 256–265 (2017).

    [126] K. Gou, Y. Li, Y. Qu, H. Li, R. Zeng, Advances and prospects of Bletilla striata polysaccharide as promising multifunctional biomedical materials. Mater. Des. 223, 111198 (2022).

    [127] Z. Chen, L. Cheng, Y. He, X. Wei, Extraction, characterization, utilization as wound dressing and drug delivery of Bletilla striata polysaccharide: a review. Int. J. Biol. Macromol. 120, 2076–2085 (2018).

    [128] L. Bai, T. Wang, Q. Deng, W. Zheng, X. Li et al., Dual properties of pharmacological activities and preparation excipient: Bletilla striata polysaccharides. Int. J. Biol. Macromol. (2023).

    [129] L. Hu, Z. Liao, Q. Hu, K.G. Maffucci, Y. Qu, Novel Bletilla striata polysaccharide microneedles: fabrication, characterization, and in vitro transcutaneous drug delivery. Int. J. Biol. Macromol. 117, 928–936 (2018).

    [130] M.K. Chan, Y. Yu, S. Wulamu, Y. Wang, Q. Wang et al., Structural analysis of water-soluble polysaccharides isolated from panax notoginseng. Int. J. Biol. Macromol. 155, 376–385 (2020).

    [131] C. Wang, S. Liu, J. Xu, M. Gao, Y. Qu et al., Dissolvable microneedles based on panax notoginseng polysaccharide for transdermal drug delivery and skin dendritic cell activation. Carbohyd. Polym. 268, 118211 (2021).

    [132] R.F. Donnelly, D.I. Morrow, T.R. Singh, K. Migalska, P.A. McCarron et al., Processing difficulties and instability of carbohydrate microneedle arrays. Drug Dev. Ind. Pharm. 35, 1242–1254 (2009).

    [133] M.J. Mistilis, J.C. Joyce, E.S. Esser, I. Skountzou, R.W. Compans et al., Long-term stability of influenza vaccine in a dissolving microneedle patch. Drug Deliv. Transl. Res. 7, 195–205 (2017).

    [134] L. Yenkoidiok-Douti, C. Barillas-Mury, C.M. Jewell, Design of dissolvable microneedles for delivery of a Pfs47-based malaria transmission-blocking vaccine. ACS Biomater. Sci. Eng. 7, 1854–1862 (2021).

    [135] L.Y. Chu, L. Ye, K. Dong, R.W. Compans, C. Yang et al., Enhanced stability of inactivated influenza vaccine encapsulated in dissolving microneedle patches. Pharm. Res. 33, 868–878 (2016).

    [136] D.D. Zhu, X.P. Zhang, H.L. Yu, R.X. Liu, C.B. Shen et al., Kinetic stability studies of HBV vaccine in a microneedle patch. Int. J. Pharm. 567, 118489 (2019).

    [137] Y. Lee, W. Li, J. Tang, S.P. Schwendeman, M.R. Prausnitz, Immediate detachment of microneedles by interfacial fracture for sustained delivery of a contraceptive hormone in the skin. J. Control. Release 337, 676–685 (2021).

    [138] A. Kumar, K.M. Rao, S.S. Han, Application of xanthan gum as polysaccharide in tissue engineering: a review. Carbohyd. Polym. 180, 128–144 (2018).

    [139] P.S. Gils, D. Ray, P.K. Sahoo, Characteristics of xanthan gum-based biodegradable superporous hydrogel. Int. J. Biol. Macromol. 45, 364–371 (2009).

    [140] P. Rakshit, T.K. Giri, K. Mukherjee, Research progresses on carboxymethyl xanthan gum: review of synthesis, physicochemical properties, rheological characterization and applications in drug delivery. Int. J. Biol. Macromol. 266, 131122 (2024).

    [141] Y. Bachra, A. Grouli, F. Damiri, M. Talbi, M. Berrada, A novel superabsorbent polymer from crosslinked carboxymethyl tragacanth gum with glutaraldehyde: synthesis, characterization, and swelling properties. Int. J. Biomater. 2021, 5008833 (2021).

    [142] H.-J. Choi, J.-M. Song, B.J. Bondy, R.W. Compans, S.-M. Kang et al., Effect of osmotic pressure on the stability of whole inactivated influenza vaccine for coating on microneedles. PLoS ONE 10, e0134431 (2015).

    [143] H. Xiang, S. Xu, W. Zhang, Y. Li, Y. Zhou et al., Skin permeation of curcumin nanocrystals: effect of particle size, delivery vehicles, and permeation enhancer. Colloids Surf. B Biointerfaces 224, 113203 (2023).

    [144] L.-D. Koh, Y. Cheng, C.-P. Teng, Y.-W. Khin, X.-J. Loh et al., Structures, mechanical properties and applications of silk fibroin materials. Prog. Polym. Sci. 46, 86–110 (2015).

    [145] E. Wenk, H.P. Merkle, L. Meinel, Silk fibroin as a vehicle for drug delivery applications. J. Control. Release 150, 128–141 (2011).

    [146] J. Lee, E.H. Jang, J.H. Kim, S. Park, Y. Kang et al., Highly flexible and porous silk fibroin microneedle wraps for perivascular drug delivery. J. Control. Release 340, 125–135 (2021).

    [147] M. Zhu, Y. Liu, F. Jiang, J. Cao, S.C. Kundu et al., Combined silk fibroin microneedles for insulin delivery. ACS Biomater. Sci. Eng. 6, 3422–3429 (2020).

    [148] Y. Gao, M. Hou, R. Yang, L. Zhang, Z. Xu et al., Highly porous silk fibroin scaffold packed in PEGDA/sucrose microneedles for controllable transdermal drug delivery. Biomacromol 20, 1334–1345 (2019).

    [149] Z. Yin, D. Kuang, S. Wang, Z. Zheng, V.K. Yadavalli et al., Swellable silk fibroin microneedles for transdermal drug delivery. Int. J. Biol. Macromol. 106, 48–56 (2018).

    [150] M.R. Babu, S. Vishwas, R. Khursheed, V. Harish, A.B. Sravani et al., Unravelling the role of microneedles in drug delivery: principle, perspectives, and practices. Drug Deliv. Transl. Res. 14, 1393–1431 (2023).

    [151] T. Zhu, W. Zhang, P. Jiang, S. Zhou, C. Wang et al., Progress in intradermal and transdermal gene therapy with microneedles. Pharm. Res. 39, 2475–2486 (2022).

    [152] S. Khan, A. Hasan, F. Attar, M.M.N. Babadaei, H.A. Zeinabad et al., Diagnostic and drug release systems based on microneedle arrays in breast cancer therapy. J. Control. Release 338, 341–357 (2021).

    [153] P. Rana, A.D. Dey, T. Agarwal, A. Kumar, Microneedles for delivery of anticancer therapeutics: recent trends and technologies. J. Nanopart. Res. 25, 154 (2023).

    [154] J.Y. Park, Treatment of intraocular lymphoma using biodegradable microneedle implant. 139 (2007). https://europepmc.org/article/ETH/3418

    [155] J. Jiang, H.S. Gill, D. Ghate, B.E. McCarey, S.R. Patel et al., Coated microneedles for drug delivery to the eye. Invest. Ophthalmol. Vis. Sci. 48, 4038–4043 (2007).

    [156] Y.C. Kim, M.R. Prausnitz, H.F. Edelhauser, Targeted delivery of anti-glaucoma drugs to the supraciliary space using microneedles. Invest. Ophthalmol. Vis. Sci. 55, 5257–5257 (2014).

    [157] H.B. Song, K.J. Lee, I.H. Seo, J.Y. Lee, S.-M. Lee et al., Impact insertion of transfer-molded microneedle for localized and minimally invasive ocular drug delivery. J. Control. Release 209, 272–279 (2015).

    [158] R.R.S. Thakur, I.A. Tekko, F. Al-Shammari, A.A. Ali, H. McCarthy et al., Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery. Drug Deliv. Transl. Res. 6, 800–815 (2016).

    [159] M. Amer, R.K. Chen, Self-adhesive microneedles with interlocking features for sustained ocular drug delivery. Macromol. Biosci. 20, 2000089 (2020).

    [160] M. Cui, M. Zheng, C. Wiraja, S.W.T. Chew, A. Mishra et al., Ocular delivery of predatory bacteria with cryomicroneedles against eye infection. Adv. Sci. 8, e2102327 (2021).

    [161] G. Roy, P. Garg, V.V.K. Venuganti, Microneedle scleral patch for minimally invasive delivery of triamcinolone to the posterior segment of eye. Int. J. Pharm. 612, 121305 (2022).

    [162] Y. Fang, L. Zhuo, H. Yuan, H. Zhao, L. Zhang, Construction of graphene quantum dot-based dissolving microneedle patches for the treatment of bacterial keratitis. Int. J. Pharm. 639, 122945 (2023).

    [163] X. Jiang, Y. Jin, Y. Zeng, P. Shi, W. Li, Self-implantable core–shell microneedle patch for long-acting treatment of keratitis via programmed drug release. Small (2024).

    [164] T. Miyano, Y. Tobinaga, T. Kanno, Y. Matsuzaki, H. Takeda et al., Sugar micro needles as transdermic drug delivery system. Biomed. Microdevices 7, 185–188 (2005).

    [165] Y. Wu, L.K. Vora, D. Mishra, M.F. Adrianto, S. Gade et al., Nanosuspension-loaded dissolving bilayer microneedles for hydrophobic drug delivery to the posterior segment of the eye. Biomater. Adv. 137, 212767 (2022).

    [166] M.G. McGrath, S. Vucen, A. Vrdoljak, A. Kelly, C. O’Mahony et al., Production of dissolvable microneedles using an atomised spray process: effect of microneedle composition on skin penetration. Eur. J. Pharm. Biopharm. 86, 200–211 (2014).

    [167] B.-M. Lee, C. Lee, S.F. Lahiji, U.-W. Jung, G. Chung et al., Dissolving microneedles for rapid and painless local anesthesia. Pharmaceutics 12, 366 (2020).

    [168] W. Zhu, W. Pewin, C. Wang, Y. Luo, G.X. Gonzalez et al., A boosting skin vaccination with dissolving microneedle patch encapsulating M2e vaccine broadens the protective efficacy of conventional influenza vaccines. J. Control. Release 261, 1–9 (2017).

    [169] N.W. Kim, S.-Y. Kim, J.E. Lee, Y. Yin, J.H. Lee et al., Enhanced cancer vaccination by in situ nanomicelle-generating dissolving microneedles. ACS Nano 12, 9702–9713 (2018).

    [170] L.E. Moore, S. Vucen, A.C. Moore, Trends in drug-and vaccine-based dissolvable microneedle materials and methods of fabrication. Eur. J. Pharm. Biopharm. 173, 54–72 (2022).

    [171] C. Kuwentrai, J. Yu, L. Rong, B.Z. Zhang, Y.F. Hu et al., Intradermal delivery of receptor-binding domain of SARS-CoV-2 spike protein with dissolvable microneedles to induce humoral and cellular responses in mice. Bioeng. Transl. Med. 6, e10202 (2021).

    [172] A. Donadei, H. Kraan, O. Ophorst, O. Flynn, C. O’Mahony et al., Skin delivery of trivalent sabin inactivated poliovirus vaccine using dissolvable microneedle patches induces neutralizing antibodies. J. Control. Release 311, 96–103 (2019).

    [173] M.-C. Chen, K.-Y. Lai, M.-H. Ling, C.-W. Lin, Enhancing immunogenicity of antigens through sustained intradermal delivery using chitosan microneedles with a patch-dissolvable design. Acta Biomater. 65, 66–75 (2018).

    [174] E. Kim, G. Erdos, S. Huang, T.W. Kenniston, S.C. Balmert et al., Microneedle array delivered recombinant coronavirus vaccines: immunogenicity and rapid translational development. EBioMedicine 55, 102743 (2020).

    [175] P.R. Yadav, M.N. Munni, L. Campbell, G. Mostofa, L. Dobson et al., Translation of polymeric microneedles for treatment of human diseases: recent trends, progress, and challenges. Pharmaceutics 13, 1132 (2021).

    [176] R. Jamaledin, C. Di Natale, V. Onesto, Z.B. Taraghdari, E.N. Zare et al., Progress in microneedle-mediated protein delivery. J. Clin. Med. 9, 542 (2020).

    [177] D. Jakka, A.V. Matadh, V.K. Shankar, H. Shivakumar, S.N. Murthy, Polymer coated polymeric (PCP) microneedles for controlled delivery of drugs (dermal and intravitreal). J. Pharm. Sci. 111, 2867–2878 (2022).

    [178] H. Chang, M. Zheng, X. Yu, A. Than, R.Z. Seeni et al., A swellable microneedle patch to rapidly extract skin interstitial fluid for timely metabolic analysis. Adv. Mater. 29, 1702243 (2017).

    [179] H.S. Gill, M.R. Prausnitz, Coated microneedles for transdermal delivery. J. Control. Release 117, 227–237 (2007).

    [180] W. Li, G. Hua, J. Cai, Y. Zhou, X. Zhou et al., Multi-stimulus responsive multilayer coating for treatment of device-associated infections. J. Funct. Biomater. 13, 24 (2022).

    [181] Y. Chen, B.Z. Chen, Q.L. Wang, X. Jin, X.D. Guo, Fabrication of coated polymer microneedles for transdermal drug delivery. J. Control. Release 265, 14–21 (2017).

    [182] S. Li, W. Li, M. Prausnitz, Individually coated microneedles for co-delivery of multiple compounds with different properties. Drug Deliv. Transl. Res. 8, 1043–1052 (2018).

    [183] R.H. Chong, E. Gonzalez-Gonzalez, M.F. Lara, T.J. Speaker, C.H. Contag et al., Gene silencing following siRNA delivery to skin via coated steel microneedles: in vitro and in vivo proof-of-concept. J. Control. Release 166, 211–219 (2013).

    [184] Y. Shin, J. Kim, J.H. Seok, H. Park, H.-R. Cha et al., Development of the H3N2 influenza microneedle vaccine for cross-protection against antigenic variants. Sci. Rep. 12, 12189 (2022).

    [185] J.G. Turner, L.R. White, P. Estrela, H.S. Leese, Hydrogel-forming microneedles: current advancements and future trends. Macromol. Biosci. 21, 2000307 (2021).

    [186] M. Kim, B. Jung, J.-H. Park, Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin. Biomaterials 33, 668–678 (2012).

    [187] H. Dawud, N. Edelstein-Pardo, K. Mulamukkil, R.J. Amir, A. Abu Ammar, Hydrogel microneedles with programmed mesophase transitions for controlled drug delivery. ACS Appl. Bio Mater. 7, 1682–1693 (2024).

    [188] Z. Li, P. Zhao, Z. Ling, Y. Zheng, F. Qu et al., An ultraswelling microneedle device for facile and efficient drug loading and transdermal delivery. Adv. Healthc. Mater. 13, 2302406 (2024).

    [189] R.F. Donnelly, M.T. McCrudden, A. Zaid Alkilani, E. Larrañeta, E. McAlister et al., Hydrogel-forming microneedles prepared from “super swelling” polymers combined with lyophilised wafers for transdermal drug delivery. PLoS ONE 9, e111547 (2014).

    [190] J. Zhu, X. Zhou, H.J. Kim, M. Qu, X. Jiang et al., Gelatin methacryloyl microneedle patches for minimally invasive extraction of skin interstitial fluid. Small 16, 1905910 (2020).

    [191] X. Hong, Z. Wu, L. Chen, F. Wu, L. Wei et al., Hydrogel microneedle arrays for transdermal drug delivery. Nano-Micro Lett. 6, 191–199 (2014).

    [192] E. Caffarel-Salvador, A.J. Brady, E. Eltayib, T. Meng, A. Alonso-Vicente et al., Hydrogel-forming microneedle arrays allow detection of drugs and glucose in vivo: potential for use in diagnosis and therapeutic drug monitoring. PLoS ONE 10, e0145644 (2015).

    [193] M.T. Hoang, K.B. Ita, D.A. Bair, Solid microneedles for transdermal delivery of amantadine hydrochloride and pramipexole dihydrochloride. Pharmaceutics 7, 379–396 (2015).

    [194] F.K. Aldawood, A. Andar, S. Desai, A comprehensive review of microneedles: types, materials, processes, characterizations and applications. Polymers 13, 2815 (2021).

    [195] C.E. Umeyor, V. Shelke, A. Pol, P. Kolekar, S. Jadhav et al., Biomimetic microneedles: Exploring the recent advances on a microfabricated system for precision delivery of drugs, peptides, and proteins. Future J. Pharm. Sci. 9, 103 (2023).

    [196] S. Pradeep Narayanan, S. Raghavan, Solid silicon microneedles for drug delivery applications. Int. J. Adv. Manuf. Technol. 93, 407–422 (2017).

    [197] W. Li, Y.M. Zhang, J. Chen, Design, fabrication and characterization of in-plane titanium microneedles for transdermal drug delivery. Key Eng. Mater. 483, 532–536 (2011).

    [198] Z. Ding, F.J. Verbaan, M. Bivas-Benita, L. Bungener, A. Huckriede et al., Microneedle arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice. J. Control. Release 136, 71–78 (2009).

    [199] Q.Y. Li, J.N. Zhang, B.Z. Chen, Q.L. Wang, X.D. Guo, A solid polymer microneedle patch pretreatment enhances the permeation of drug molecules into the skin. RSC Adv. 7, 15408–15415 (2017).

    [200] W. Shu, H. Heimark, N. Bertollo, D.J. Tobin, E.D. O’Cearbhaill et al., Insights into the mechanics of solid conical microneedle array insertion into skin using the finite element method. Acta Biomater. 135, 403–413 (2021).

    [201] N.N. Ahmad, N.N.N. Ghazali, Y.H. Wong, Mechanical and fluidic analysis of hollow side-open and outer-grooved design of microneedles. Mater. Today Commun. 29, 102940 (2021).

    [202] L. Huang, H. Fang, T. Zhang, B. Hu, S. Liu et al., Drug-loaded balloon with built-in nir controlled tip-separable microneedles for long-effective arteriosclerosis treatment. Bioact. Mater. 23, 526–538 (2023).

    [203] E. Larrañeta, R.E. Lutton, A.D. Woolfson, R.F. Donnelly, Microneedle arrays as transdermal and intradermal drug delivery systems: materials science, manufacture and commercial development. Mater. Sci. Eng. R. Rep. 104, 1–32 (2016).

    [204] S.R. Patel, A.S. Lin, H.F. Edelhauser, M.R. Prausnitz, Suprachoroidal drug delivery to the back of the eye using hollow microneedles. Pharm. Res. 28, 166–176 (2011).

    [205] K. van der Maaden, J. Heuts, M. Camps, M. Pontier, A.T. van Scheltinga et al., Hollow microneedle-mediated micro-injections of a liposomal HPV E743–63 synthetic long peptide vaccine for efficient induction of cytotoxic and t-helper responses. J. Control. Release 269, 347–354 (2018).

    [206] M. Fratus, M.A. Alam, Theory of nanostructured sensors integrated in/on microneedles for diagnostics and therapy. Biosens. Bioelectron. 255, 116238 (2024).

    [207] X. Zhang, G. Chen, L. Cai, Y. Wang, L. Sun et al., Bioinspired pagoda-like microneedle patches with strong fixation and hemostasis capabilities. Chem. Eng. J. 414, 128905 (2021).

    [208] W.-G. Bae, H. Ko, J.-Y. So, H. Yi, C.-H. Lee et al., Snake fang–inspired stamping patch for transdermal delivery of liquid formulations. Sci. Transl. Med. 11, eaaw3329 (2019).

    [209] W.K. Cho, J.A. Ankrum, D. Guo, S.A. Chester, S.Y. Yang et al., Microstructured barbs on the North American porcupine quill enable easy tissue penetration and difficult removal. Proc. Natl. Acad. Sci. U.S.A. 109, 21289–21294 (2012).

    [210] X. Zhang, G. Chen, L. Sun, F. Ye, X. Shen et al., Claw-inspired microneedle patches with liquid metal encapsulation for accelerating incisional wound healing. Chem. Eng. J. 406, 126741 (2021).

    [211] Y. Deng, C. Yang, Y. Zhu, W. Liu, H. Li et al., Lamprey-teeth-inspired oriented antibacterial sericin microneedles for infected wound healing improvement. Nano Lett. 22, 2702–2711 (2022).

    [212] M. Guo, Y. Wang, B. Gao, B. He, Shark tooth-inspired microneedle dressing for intelligent wound management. ACS Nano 15, 15316–15327 (2021).

    [213] Z. Zhu, J. Wang, X. Pei, J. Chen, X. Wei et al., Blue-ringed octopus-inspired microneedle patch for robust tissue surface adhesion and active injection drug delivery. Sci. Adv. 9, eadh2213 (2023).

    [214] K. Moussi, A.A. Haneef, R.A. Alsiary, E.M. Diallo, M.A. Boone et al., A microneedles balloon catheter for endovascular drug delivery. Adv. Mater. Technol. 6, 2100037 (2021).

    [215] K. Lee, J. Lee, S.G. Lee, S. Park, J.-J. Lee et al., Microneedle drug eluting balloon for enhanced drug delivery to vascular tissue. J. Control. Release 321, 174–183 (2020).

    [216] J. Luo, J.-K. Wang, B.-L. Song, Lowering low-density lipoprotein cholesterol: from mechanisms to therapies. Life Metab. 1, 25–38 (2022).

    [217] X. Zhang, Y. Cheng, R. Liu, Y. Zhao, Globefish-inspired balloon catheter with intelligent microneedle coating for endovascular drug delivery. Adv. Sci. 9, 2204497 (2022).

    [218] J.M. Loh, Y.J.L. Lim, J.T. Tay, H.M. Cheng, H.L. Tey et al., Design and fabrication of customizable microneedles enabled by 3D printing for biomedical applications. Bioact. Mater. 32, 222–241 (2024).

    [219] C. Yeung, S. Chen, B. King, H. Lin, K. King et al., A 3D-printed microfluidic-enabled hollow microneedle architecture for transdermal drug delivery. Biomicrofluidics 13, 064125 (2019).

    [220] P.R. Miller, S.D. Gittard, T.L. Edwards, D.M. Lopez, X. Xiao et al., Integrated carbon fiber electrodes within hollow polymer microneedles for transdermal electrochemical sensing. Biomicrofluidics 5, 013415 (2011).

    [221] L. Zheng, D. Zhu, Y. Xiao, X. Zheng, P. Chen, Microneedle coupled epidermal sensor for multiplexed electrochemical detection of kidney disease biomarkers. Biosens. Bioelectron. 237, 115506 (2023).

    [222] L. Lin, Y. Wang, M. Cai, X. Jiang, Y. Hu et al., Multimicrochannel microneedle microporation platform for enhanced intracellular drug delivery. Adv. Funct. Mater. 32, 2109187 (2022).

    [223] C. Farias, R. Lyman, C. Hemingway, H. Chau, A. Mahacek et al., Three-dimensional (3D) printed microneedles for microencapsulated cell extrusion. Bioengineering 5, 59 (2018).

    [224] S. Wang, M. Zhao, Y. Yan, P. Li, W. Huang, Flexible monitoring, diagnosis, and therapy by microneedles with versatile materials and devices toward multifunction scope. Research 6, 0128 (2023).

    [225] M. Tavafoghi, F. Nasrollahi, S. Karamikamkar, M. Mahmoodi, S. Nadine et al., Advances and challenges in developing smart, multifunctional microneedles for biomedical applications. Biotechnol. Bioeng. 119, 2715–2730 (2022).

    [226] Y. Zhou, B. Niu, Y. Zhao, J. Fu, T. Wen et al., Multifunctional nanoreactors-integrated microneedles for cascade reaction-enhanced cancer therapy. J. Control. Release 339, 335–349 (2021).

    [227] A. Tucak, M. Sirbubalo, L. Hindija, O. Rahić, J. Hadžiabdić et al., Microneedles: characteristics, materials, production methods and commercial development. Micromachines 11, 961 (2020).

    [228] Y. Su, V.L. Mainardi, H. Wang, A. McCarthy, Y.S. Zhang et al., Dissolvable microneedles coupled with nanofiber dressings eradicate biofilms via effectively delivering a database-designed antimicrobial peptide. ACS Nano 14, 11775–11786 (2020).

    [229] H. Yang, S. Kim, I. Huh, S. Kim, S.F. Lahiji et al., Rapid implantation of dissolving microneedles on an electrospun pillar array. Biomaterials 64, 70–77 (2015).

    [230] J.D. Kim, M. Kim, H. Yang, K. Lee, H. Jung, Droplet-born air blowing: novel dissolving microneedle fabrication. J. Control. Release 170, 430–436 (2013).

    [231] K. Lee, C.Y. Lee, H. Jung, Dissolving microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose. Biomaterials 32, 3134–3140 (2011).

    [232] S. Fakhraei Lahiji, Y. Kim, G. Kang, S. Kim, S. Lee et al., Tissue interlocking dissolving microneedles for accurate and efficient transdermal delivery of biomolecules. Sci. Rep. 9, 7886 (2019).

    [233] Q.L. Wang, D.D. Zhu, Y. Chen, X.D. Guo, A fabrication method of microneedle molds with controlled microstructures. Mater. Sci. Eng. C 65, 135–142 (2016).

    [234] P. Singh, A. Carrier, Y. Chen, S. Lin, J. Wang et al., Polymeric microneedles for controlled transdermal drug delivery. J. Control. Release 315, 97–113 (2019).

    [235] K. Badnikar, S.N. Jayadevi, S. Pahal, S. Sripada, M.M. Nayak et al., Generic molding platform for simple, low-cost fabrication of polymeric microneedles. Macromol. Mater. Eng. 305, 2000072 (2020).

    [236] M.J. Kim, S.C. Park, S.-O. Choi, Dual-nozzle spray deposition process for improving the stability of proteins in polymer microneedles. RSC Adv. 7, 55350–55359 (2017).

    [237] B. Bediz, E. Korkmaz, R. Khilwani, C. Donahue, G. Erdos et al., Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application. Pharm. Res. 31, 117–135 (2014).

    [238] J.W. Lee, J.-H. Park, M.R. Prausnitz, Dissolving microneedles for transdermal drug delivery. Biomaterials 29, 2113–2124 (2008).

    [239] S.P. Sullivan, N. Murthy, M.R. Prausnitz, Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Adv. Mater. 20, 933–938 (2008).

    [240] S.C. Park, M.J. Kim, S.-K. Baek, J.-H. Park, S.-O. Choi, Spray-formed layered polymer microneedles for controlled biphasic drug delivery. Polymers 11, 369 (2019).

    [241] K. Valachová, M.A. El Meligy, L. Šoltés, Hyaluronic acid and chitosan-based electrospun wound dressings: problems and solutions. Int. J. Biol. Macromol. 206, 74–91 (2022).

    [242] R. Augustine, S.R.U. Rehman, R. Ahmed, A.A. Zahid, M. Sharifi et al., Electrospun chitosan membranes containing bioactive and therapeutic agents for enhanced wound healing. Int. J. Biol. Macromol. 156, 153–170 (2020).

    [243] B.P. Antunes, A.F. Moreira, V.M. Gaspar, I.J. Correia, Chitosan/arginine–chitosan polymer blends for assembly of nanofibrous membranes for wound regeneration. Carbohyd. Polym. 130, 104–112 (2015).

    [244] Y. Wang, P. Guan, R. Tan, Z. Shi, Q. Li et al., Fiber-reinforced silk microneedle patches for improved tissue adhesion in treating diabetic wound infections. Adv. Fiber Mater. (2024).

    [245] L. Fu, Q. Feng, Y. Chen, J. Fu, X. Zhou et al., Nanofibers for the immunoregulation in biomedical applications. Adv. Fiber Mater. 4, 1334–1356 (2022).

    [246] H. He, M. Wu, J. Zhu, Y. Yang, R. Ge et al., Engineered spindles of little molecules around electrospun nanofibers for biphasic drug release. Adv. Fiber Mater. 4, 305–317 (2022).

    [247] Y. Long, L. Li, T. Xu, X. Wu, Y. Gao et al., Hedgehog artificial macrophage with atomic-catalytic centers to combat drug-resistant bacteria. Nat. Commun. 12, 6143 (2021).

    [248] S. Xiao, L. Xie, Y. Gao, M. Wang, W. Geng et al., Artificial phages with biocatalytic spikes for synergistically eradicating antibiotic-resistant biofilms. Adv. Mater. (2024).

    [249] H.K. Azar, M.H. Monfared, A.A. Seraji, S. Nazarnezhad, E. Nasiri et al., Integration of polysaccharide electrospun nanofibers with microneedle arrays promotes wound regeneration: a review. Int. J. Biol. Macromol. 258, 128482 (2023).

    [250] S. Bhatnagar, P.R. Gadeela, P. Thathireddy, V.V.K. Venuganti, Microneedle-based drug delivery: materials of construction. J. Chem. Sci. 131, 1–28 (2019).

    [251] M. Ali, S. Namjoshi, H.A. Benson, Y. Mohammed, T. Kumeria, Dissolvable polymer microneedles for drug delivery and diagnostics. J. Control. Release 347, 561–589 (2022).

    [252] S.N. Economidou, C.P.P. Pere, A. Reid, M.J. Uddin, J.F. Windmill et al., 3D printed microneedle patches using stereolithography (SLA) for intradermal insulin delivery. Mater. Sci. Eng. C 102, 743–755 (2019).

    [253] K. Lee, H.C. Lee, D.S. Lee, H. Jung, Drawing lithography: three-dimensional fabrication of an ultrahigh-aspect-ratio microneedle. Adv. Mater. 22, 483–486 (2010).

    [254] R. Vecchione, S. Coppola, E. Esposito, C. Casale, V. Vespini et al., Electro-drawn drug-loaded biodegradable polymer microneedles as a viable route to hypodermic injection. Adv. Funct. Mater. 24, 3515–3523 (2014).

    [255] Z. Chen, L. Ren, J. Li, L. Yao, Y. Chen et al., Rapid fabrication of microneedles using magnetorheological drawing lithography. Acta Biomater. 65, 283–291 (2018).

    [256] F. Ruggiero, R. Vecchione, S. Bhowmick, G. Coppola, S. Coppola et al., Electro-drawn polymer microneedle arrays with controlled shape and dimension. Sens. Actuators B Chem. 255, 1553–1560 (2018).

    [257] H. Yang, S. Kim, G. Kang, S.F. Lahiji, M. Jang et al., Centrifugal lithography: self-shaping of polymer microstructures encapsulating biopharmaceutics by centrifuging polymer drops. Adv. Healthc. Mater. 6, 1700326 (2017).

    [258] I. Huh, S. Kim, H. Yang, M. Jang, G. Kang et al., Effects of two droplet-based dissolving microneedle manufacturing methods on the activity of encapsulated epidermal growth factor and ascorbic acid. Eur. J. Pharm. Sci. 114, 285–292 (2018).

    [259] C. Lee, H. Kim, S. Kim, S.F. Lahiji, N.Y. Ha et al., Comparative study of two droplet-based dissolving microneedle fabrication methods for skin vaccination. Adv. Healthc. Mater. 7, 1701381 (2018).

    [260] M. Olowe, S.K. Parupelli, S. Desai, A review of 3D-printing of microneedles. Pharmaceutics 14, 2693 (2022).

    [261] M.A. Luzuriaga, D.R. Berry, J.C. Reagan, R.A. Smaldone, J.J. Gassensmith, Biodegradable 3D printed polymer microneedles for transdermal drug delivery. Lab Chip 18, 1223–1230 (2018).

    [262] L. Wu, J. Park, Y. Kamaki, B. Kim, Optimization of the fused deposition modeling-based fabrication process for polylactic acid microneedles. Microsyst. Nanoeng. 7, 58 (2021).

    [263] U. Detamornrat, E. McAlister, A.R. Hutton, E. Larrañeta, R.F. Donnelly, The role of 3D printing technology in microengineering of microneedles. Small 18, 2106392 (2022).

    [264] R. Wichniarek, W. Kuczko, D. Tomczak, A. Nowicka, M. Wojtyłko et al., Geometrical accuracy and strength of micro-needles made of polylactide by fused filament fabrication method. Adv. Colloid Interface Sci. 17, 116–126 (2023).

    [265] C.P.P. Pere, S.N. Economidou, G. Lall, C. Ziraud, J.S. Boateng et al., 3D printed microneedles for insulin skin delivery. Int. J. Pharm. 544, 425–432 (2018).

    [266] K.J. Krieger, N. Bertollo, M. Dangol, J.T. Sheridan, M.M. Lowery et al., Simple and customizable method for fabrication of high-aspect ratio microneedle molds using low-cost 3D printing. Microsyst. Nanoeng. 5, 42 (2019).

    [267] S. Choo, S. Jin, J. Jung, Fabricating high-resolution and high-dimensional microneedle mold through the resolution improvement of stereolithography 3D printing. Pharmaceutics 14, 766 (2022).

    [268] A. Bertino, L. Mazzeo, G. Caputo, S. Sau, A. Giaconia et al., Continuous multiphase bunsen reactor of iodine–sulfur thermochemical water splitting cycles for hydrogen production: experimental, modelling and design insights. Chem. Eng. J. 481, 148415 (2024).

    [269] D. Shin, J. Hyun, Silk fibroin microneedles fabricated by digital light processing 3D printing. J. Ind. Eng. Chem. 95, 126–133 (2021).

    [270] A. Ovsianikov, B. Chichkov, P. Mente, N. Monteiro-Riviere, A. Doraiswamy et al., Two photon polymerization of polymer–ceramic hybrid materials for transdermal drug delivery. Int. J. Appl. Ceram. Technol. 4, 22–29 (2007).

    [271] D. Han, R.S. Morde, S. Mariani, A.A. La Mattina, E. Vignali et al., 4D printing of a bioinspired microneedle array with backward-facing barbs for enhanced tissue adhesion. Adv. Funct. Mater. 30, 1909197 (2020).

    [272] R. Parhi, Recent advances in 3D printed microneedles and their skin delivery application in the treatment of various diseases. J. Drug Deliv. Sci. Technol. 84, 104395 (2023).

    [273] H. Ako, J. O’Mahony, H. Hughes, P. McLoughlin, N.J. O’Reilly, A novel approach to the manufacture of dissolving microneedles arrays using aerosol jet printing. Appl. Mater. Today 35, 101958 (2023).

    [274] Y. Li, K. Chen, Y. Pang, J. Zhang, M. Wu et al., Multifunctional microneedle patches via direct ink drawing of nanocomposite inks for personalized transdermal drug delivery. ACS Nano 17, 19925–19937 (2023).

    [275] R. Li, L. Zhang, X. Jiang, L. Li, S. Wu et al., 3D-printed microneedle arrays for drug delivery. J. Control. Release 350, 933–948 (2022).

    [276] J.R. Tumbleston, D. Shirvanyants, N. Ermoshkin, R. Janusziewicz, A.R. Johnson et al., Continuous liquid interface production of 3D objects. Science 347, 1349–1352 (2015).

    [277] S.S. Al-Nimry, R.M. Daghmash, Three dimensional printing and its applications focusing on microneedles for drug delivery. Pharmaceutics 15, 1597 (2023).

    [278] S.N. Economidou, C.P. Pissinato Pere, M. Okereke, D. Douroumis, Optimisation of design and manufacturing parameters of 3D printed solid microneedles for improved strength, sharpness, and drug delivery. Micromachines 12, 117 (2021).

    [279] S. Feng, J. Delannoy, A. Malod, H. Zheng, D. Quéré et al., Tip-induced flipping of droplets on Janus pillars: from local reconfiguration to global transport. Sci. Adv. 6, eabb4540 (2020).

    [280] Y. Zambito, G. Di Colo, Polysaccharides as excipients for ocular topical formulations, Biomaterials Applications for Nanomedicine, (2011), pp. 253–280.

    [281] R.V. Moiseev, P.W. Morrison, F. Steele, V.V. Khutoryanskiy, Penetration enhancers in ocular drug delivery. Pharmaceutics 11, 321 (2019).

    [282] R.N. Van Gelder, M.F. Chiang, M.A. Dyer, T.N. Greenwell, L.A. Levin et al., Regenerative and restorative medicine for eye disease. Nat. Med. 28, 1149–1156 (2022).

    [283] Y.-Y. Leong, L. Tong, Barrier function in the ocular surface: from conventional paradigms to new opportunities. Ocul. Surf. 13, 103–109 (2015).

    [284] R.D. Bachu, P. Chowdhury, Z.H. Al-Saedi, P.K. Karla, S.H. Boddu, Ocular drug delivery barriers—role of nanocarriers in the treatment of anterior segment ocular diseases. Pharmaceutics 10, 28 (2018).

    [285] E. Mott, H. Kesten, Eye hypersensitivity elicited by monilia psilosis polysaccharide. Proc. Soc. Exp. Biol. Med. 28, 320–321 (1930).

    [286] M. Rolando, C. Valente, Establishing the tolerability and performance of tamarind seed polysaccharide (TSP) in treating dry eye syndrome: results of a clinical study. BMC Ophthalmol. 7, 5 (2007).

    [287] E. Mott, H.D. Kesten, Hypersensitiveness to soluble specific substances from yeast-like fungi : Ii. eye hypersensitivity. J. Exp. Med. 53, 815–819 (1931).

    [288] X.-G. Wu, M. Xin, H. Chen, L.-N. Yang, H.-R. Jiang, Novel mucoadhesive polysaccharide isolated from Bletilla striata improves the intraocular penetration and efficacy of levofloxacin in the topical treatment of experimental bacterial keratitis. J. Pharm. Pharmacol. 62, 1152–1157 (2010).

    [289] E. Akbari, R. Imani, P. Shokrollahi, R. Jarchizadeh, Hydrogel-based formulations for drug delivery to the anterior segment of the eye. J. Drug Deliv. Sci. Technol. 81, 104250 (2023).

    [290] H. Yu, W. Wu, X. Lin, Y. Feng, Polysaccharide-based nanomaterials for ocular drug delivery: a perspective. Front. Bioeng. Biotechnol. 8, 601246 (2020).

    [291] J. Necas, L. Bartosikova, P. Brauner, J. Kolar, Hyaluronic acid (hyaluronan): a review. Vet. Med. 53, 397–411 (2008).

    [292] I. Hargittai, M. Hargittai, Molecular structure of hyaluronan: an introduction. Struct. Chem. 19, 697–717 (2008).

    [293] X. Zhang, D. Wei, Y. Xu, Q. Zhu, Hyaluronic acid in ocular drug delivery. Carbohyd. Polym. 264, 118006 (2021).

    [294] W.-H. Chang, P.-Y. Liu, M.-H. Lin, C.-J. Lu, H.-Y. Chou et al., Applications of hyaluronic acid in ophthalmology and contact lenses. Molecules 26, 2485 (2021).

    [295] J. Pinto-Fraga, A. López-de la Rosa, F.B. Arauzo, R.U. Rodríguez, M.J. González-García, Efficacy and safety of 0.2% hyaluronic acid in the management of dry eye disease. Eye Contact Lens 43, 57–63 (2017).

    [296] D. Lee, Q. Lu, S.D. Sommerfeld, A. Chan, N.G. Menon et al., Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease. Acta Biomater. 55, 163–171 (2017).

    [297] O. Galvin, A. Srivastava, O. Carroll, R. Kulkarni, S. Dykes et al., A sustained release formulation of novel quininib-hyaluronan microneedles inhibits angiogenesis and retinal vascular permeability in vivo. J. Control. Release 233, 198–207 (2016).

    [298] B. Gupta, V. Mishra, S. Gharat, M. Momin, A. Omri, Cellulosic polymers for enhancing drug bioavailability in ocular drug delivery systems. Pharmaceuticals 14, 1201 (2021).

    [299] M. Patchan, J. Graham, Z. Xia, J. Maranchi, R. McCally et al., Synthesis and properties of regenerated cellulose-based hydrogels with high strength and transparency for potential use as an ocular bandage. Mater. Sci. Eng. C 33, 3069–3076 (2013).

    [300] Y. Dong, L.I. Mosquera-Giraldo, L.S. Taylor, K.J. Edgar, Amphiphilic cellulose ethers designed for amorphous solid dispersion via olefin cross-metathesis. Biomacromol 17, 454–465 (2016).

    [301] T. Irimia, M.V. Ghica, L. Popa, V. Anuţa, A.-L. Arsene et al., Strategies for improving ocular drug bioavailability and corneal wound healing with chitosan-based delivery systems. Polymers 10, 1221 (2018).

    [302] L.M. Hemmingsen, N. Škalko-Basnet, M.W. Jøraholmen, The expanded role of chitosan in localized antimicrobial therapy. Mar. Drugs 19, 697 (2021).

    [303] A. Karava, M. Lazaridou, S. Nanaki, G. Michailidou, E. Christodoulou et al., Chitosan derivatives with mucoadhesive and antimicrobial properties for simultaneous nanoencapsulation and extended ocular release formulations of dexamethasone and chloramphenicol drugs. Pharmaceutics 12, 594 (2020).

    [304] N. Dubashynskaya, D. Poshina, S. Raik, A. Urtti, Y.A. Skorik, Polysaccharides in ocular drug delivery. Pharmaceutics 12, 22 (2019).

    [305] M. Kouchak, M. Mahmoodzadeh, F. Farrahi, Designing of a pH-triggered Carbopol®/HPMC in situ gel for ocular delivery of dorzolamide HCl: in vitro, in vivo, and ex vivo evaluation. AAPS Pharm. Sci. Tech. 20, 1–8 (2019).

    [306] X. Zhang, N. Liu, M. Zhou, T. Zhang, T. Tian et al., DNA nanorobot delivers antisense oligonucleotides silencing c-Met gene expression for cancer therapy. J. Biomed. Nanotechnol. 15, 1948–1959 (2019).

    [307] X. Wang, Q. Li, Z. Zhao, L. Yu, S. Wang et al., Dual-functional artificial peroxidases with ferriporphyrin centers for amplifying tumor immunotherapies via immunogenic cell death. Adv. Funct. Mater. 34, 2313143 (2024).

    [308] D. Yang, M. Yuan, J. Huang, X. Xiang, H. Pang et al., Conjugated network supporting highly surface-exposed Ru site-based artificial antioxidase for efficiently modulating microenvironment and alleviating solar dermatitis. ACS Nano 18, 3424–3437 (2024).

    [309] Y. Huang, X. Liu, J. Zhu, Z. Chen, L. Yu et al., Enzyme core spherical nucleic acid that enables enhanced cuproptosis and antitumor immune response through alleviating tumor hypoxia. J. Am. Chem. Soc. 146, 13805–13816 (2024).

    [310] H. Huang, W. Geng, X. Wu, Y. Zhang, L. Xie et al., Spiky artificial peroxidases with V−O−Fe pair sites for combating antibiotic-resistant pathogens. Angew. Chem. Int. Ed. 63, e202310811 (2024).

    [311] X. Qin, N. Li, M. Zhang, S. Lin, J. Zhu et al., Tetrahedral framework nucleic acids prevent retina ischemia-reperfusion injury from oxidative stress via activating the Akt/Nrf2 pathway. Nanoscale 11, 20667–20675 (2019).

    [312] X. Liu, F. Li, Z. Dong, C. Gu, D. Mao et al., Metal-polyDNA nanoparticles reconstruct osteoporotic microenvironment for enhanced osteoporosis treatment. Sci. Adv. 9, eadf329 (2023).

    [313] J.H. Jung, B. Chiang, H.E. Grossniklaus, M.R. Prausnitz, Ocular drug delivery targeted by iontophoresis in the suprachoroidal space using a microneedle. J. Control. Release 277, 14–22 (2018).

    [314] Y. Lee, S. Park, S.I. Kim, K. Lee, W. Ryu, Rapidly detachable microneedles using porous water-soluble layer for ocular drug delivery. Adv. Mater. Technol. 5, 1901145 (2020).

    [315] T. Zhong, H. Yi, J. Gou, J. Li, M. Liu et al., A wireless battery-free eye modulation patch for high myopia therapy. Nat. Commun. 15, 1766 (2024).

    [316] S.H. Park, D.H. Jo, C.S. Cho, K. Lee, J.H. Kim et al., Depthwise-controlled scleral insertion of microneedles for drug delivery to the back of the eye. Eur. J. Pharm. Biopharm. 133, 31–41 (2018).

    [317] K. Lee, H.B. Song, W. Cho, J.H. Kim, J.H. Kim et al., Intracorneal injection of a detachable hybrid microneedle for sustained drug delivery. Acta Biomater. 80, 48–57 (2018).

    [318] S. Park, K. Lee, H. Kang, Y. Lee, J. Lee et al., Single administration of a biodegradable, separable microneedle can substitute for repeated application of eyedrops in the treatment of infectious keratitis. Adv. Healthc. Mater. 10, 2002287 (2021).

    [319] W. Park, V.P. Nguyen, Y. Jeon, B. Kim, Y. Li et al., Biodegradable silicon nanoneedles for ocular drug delivery. Sci. Adv. 8, eabn1772 (2022).

    [320] T.Y. Kim, G.-H. Lee, J. Mun, S. Cheong, I. Choi et al., Smart contact lens systems for ocular drug delivery and therapy. Adv. Drug Deliv. Rev. 196, 114817 (2023).

    [321] S.K. Gade, J. Nirmal, P. Garg, V.V.K. Venuganti, Corneal delivery of moxifloxacin and dexamethasone combination using drug-eluting mucoadhesive contact lens to treat ocular infections. Int. J. Pharm. 591, 120023 (2020).

    [322] D. Datta, G. Roy, P. Garg, V.V.K. Venuganti, Ocular delivery of cyclosporine a using dissolvable microneedle contact lens. J. Drug Deliv. Sci. Technol. 70, 103211 (2022).

    Qingdong Bao, Xiaoting Zhang, Zhankun Hao, Qinghua Li, Fan Wu, Kaiyuan Wang, Yang Li, Wenlong Li, Hua Gao. Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases[J]. Nano-Micro Letters, 2024, 16(1): 268
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