Ophthalmic drug-loaded N,O-carboxymethyl chitosan hydrogels： synthesis, in vitro and in vivo evaluation

• Published in: Acta pharmacologica Sinica Vol. 31; no. 12; pp. 1625 - 1634
• Main Authors: YANG, Li-qun, LAN, Yu-qing, GUO, Hui, CHENG, Liang-zheng, FAN, Ji-zhou, CAI, Xiang, ZHANG, Li-ming, CHEN, Ru-fu, ZHOU, Huai-sheng
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.12.2010
• Subjects: Administration, Topical; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Bevacizumab; Chitosan - chemical synthesis; Chitosan - chemistry; Cicatrix - pathology; Cicatrix - prevention & control; Conjunctiva - drug effects; Conjunctiva - pathology; Conjunctiva - surgery; Cross-Linking Reagents - chemistry; Delayed-Action Preparations; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Female; Filtering Surgery; Fluorouracil - administration & dosage; Fluorouracil - chemistry; Fluorouracil - pharmacology; Glaucoma - pathology; Glaucoma - physiopathology; Glaucoma - surgery; Hydrogels; In Vitro Techniques; Intraocular Pressure; Iridoid Glycosides - chemistry; Iridoids; Male; Microscopy, Electron, Scanning; Original; Rabbits; Spectroscopy, Fourier Transform Infrared; Wound Healing - drug effects; 原位合成; 水凝胶; 紫外可见光谱; 羧甲基壳聚糖
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2010.125

Aim： To investigate the ability of drug-loaded N,O-carboxymethyl chitosan （CMCS） hydrogels to modulate wound healing after glaucoma filtration surgery. Methods： The drug-loaded CMCS hydrogels were in situ synthesized using genipin as the crosslinker in the presence of 5-fluorouracil （5FU） or bevacizumab. Their structures were characterized by FTIR, ultraviolet-visible （UV-vis） spectroscopy and scanning electron microscopy （SEM）. In-vitro drug release experiments and in vivo evaluation in rabbits were performed. Results： The results of FTIR, UV-vis spectroscopy and SEM analyses indicated that 5FU was encapsulated into the CMCS hydrogels that were crosslinked by genipin. The in vitro drug release experiments showed that nearly 100% of 5FU was released from the drug-loaded hydrogels within 8 h, but less than 20% bevacizumab was released after 53 h. The in vivo evaluation in rabbits indicated that the drug-loaded CMCS hydrogels were nontoxic to the cornea and were gradually biodegraded in the eyes. Furthermore, the drug-loaded CMCS hydrogels effectively inhibited conjunctival scarring after glaucoma filtration surgery and controlled postoperative intraocular pressure （lOP）. Conclusion： The drug-loaded CMCS hydrogets provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery.