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


CONCLUSIONS
the drug-loaded CMCS hydrogels provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery.
Institute of Polymer Science, School of Chemistry and Chemical Engineering, China. yanglq@mail.sysu.edu.cn
Li-qun
LQ
YANG
Yu-qing
YQ
LAN
Hui
H
GUO
Liang-zheng
LZ
CHENG
Ji-zhou
JZ
FAN
Xiang
X
CAI
Li-ming
LM
ZHANG
Ru-fu
RF
CHEN
Huai-sheng
HS
ZHOU
D000287:Administration, Topical; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D002921:Cicatrix / Q000473:pathology / Q000517:prevention & control; D003228:Conjunctiva / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D005260:Female; D018463:Filtering Surgery; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D005901:Glaucoma / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D020100:Hydrogels; D066298:In Vitro Techniques; D007429:Intraocular Pressure; D057889:Iridoid Glycosides / Q000737:chemistry; D039823:Iridoids; D008297:Male; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D017550:Spectroscopy, Fourier Transform Infrared; D014945:Wound Healing / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D057889:Iridoid Glycosides; D039823:Iridoids; C077199:O,N-carboxymethylchitosan; D000068258:Bevacizumab; D048271:Chitosan; C007834:genipin; D005472:Fluorouracil