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用于治疗细菌性角膜炎的载有抗菌肽的3D打印固有抗菌隐形眼镜样贴片

3D-Printed Inherently Antibacterial Contact Lens-Like Patches Carrying Antimicrobial Peptide Payload for Treating Bacterial Keratitis.

作者信息

Ch Sanjay, Mishra Priyasha, Padaga Sri Ganga, Ghosh Balaram, Roy Sanhita, Biswas Swati

机构信息

Nanomedicine Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Medchal, Hyderabad, Telangana, 500078, India.

Prof. Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad, Telangana, 500034, India.

出版信息

Macromol Biosci. 2024 Apr;24(4):e2300418. doi: 10.1002/mabi.202300418. Epub 2024 Feb 2.

Abstract

Delivery of therapeutic agents through contact lenses-like patches is a promising strategy to achieve significant bioavailability with negligible eye drainage. The present study investigates the preparation and 3D printing of mucoadhesive gelatin methacryloyl (GelMA)/chitosan methacryloyl (ChiMA) hydrogels to fabricate them as contact lens-like patches (CLP) loaded with antimicrobial peptide, S100A12 (AMP) for treating bacterial keratitis (BK). Extrusion technology is used to print the patches layer by layer to form a hemispherical scaffold suitable for eyewear, and 3D-printed CLP is crosslinked using Irgacure 2959 under UV light. The results from the in vivo experiment conducted on Pseudomonas aeruginosa-infected BK rabbit model after the treatment with AMP-loaded CLP have shown a significant decrease in bacterial load when plated for CFU. The newly developed delivery system containing AMP has great potential to overcome the treatment challenges of multidrug resistance (MDR) in bacteria and eliminate the frequent dosing associated with eye drops. The presence of chitosan in the formulation provides a synergetic effect on the AMP in disrupting bacterial biofilms. The ease of using 3D printing will open new avenues for optimizing the dosage depending on the severity of the BK in the patients, which can be used as personalized medicine.

摘要

通过隐形眼镜样贴片递送治疗剂是一种很有前景的策略,可实现显著的生物利用度,同时眼内引流可忽略不计。本研究调查了用于制备粘膜粘附性甲基丙烯酰化明胶(GelMA)/甲基丙烯酰化壳聚糖(ChiMA)水凝胶并将其3D打印,以制造载有抗菌肽S100A12(AMP)的隐形眼镜样贴片(CLP)用于治疗细菌性角膜炎(BK)。采用挤出技术逐层打印贴片,形成适合眼部佩戴的半球形支架,并在紫外光下使用Irgacure 2959对3D打印的CLP进行交联。在用载有AMP的CLP治疗后,对铜绿假单胞菌感染的BK兔模型进行的体内实验结果表明,平板接种CFU时细菌载量显著降低。新开发的含AMP递送系统具有巨大潜力,可克服细菌多药耐药性(MDR)的治疗挑战,并消除与眼药水相关的频繁给药。配方中壳聚糖的存在对AMP破坏细菌生物膜具有协同作用。3D打印的便捷性将为根据患者BK的严重程度优化剂量开辟新途径,可作为个性化药物使用。

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