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Acta Pharmacol Sin ; 31(12): 1625-34, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21042284

ABSTRACT

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 (IOP). CONCLUSION: the drug-loaded CMCS hydrogels provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Chitosan/chemistry , Drug Carriers/chemistry , Fluorouracil/administration & dosage , Administration, Topical , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized , Bevacizumab , Chitosan/chemical synthesis , Cicatrix/pathology , Cicatrix/prevention & control , Conjunctiva/drug effects , Conjunctiva/pathology , Conjunctiva/surgery , Cross-Linking Reagents/chemistry , Delayed-Action Preparations , Drug Carriers/chemical synthesis , Female , Filtering Surgery , Fluorouracil/chemistry , Fluorouracil/pharmacology , Glaucoma/pathology , Glaucoma/physiopathology , Glaucoma/surgery , Hydrogels , In Vitro Techniques , Intraocular Pressure , Iridoid Glycosides/chemistry , Iridoids , Male , Microscopy, Electron, Scanning , Rabbits , Spectroscopy, Fourier Transform Infrared , Wound Healing/drug effects
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