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

Acta Pharmacol Sin. 2010 Dec;31(12):1625-34. doi: 10.1038/aps.2010.125. Epub 2010 Nov 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Rabbits
  • Spectroscopy, Fourier Transform Infrared
  • Wound Healing / drug effects

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cross-Linking Reagents
  • Delayed-Action Preparations
  • Drug Carriers
  • Hydrogels
  • Iridoid Glycosides
  • Iridoids
  • O,N-carboxymethylchitosan
  • Bevacizumab
  • Chitosan
  • genipin
  • Fluorouracil