Chitosan-N-acetyl cysteine microspheres for ocular delivery of acyclovir: Synthesis and in vitro/in vivo evaluation

The present study was aimed at investigation of thiolated derivative of chitosan for development of microspheres for ocular delivery of the antiviral agent, acyclovir. N-Acetyl cysteine was hereby covalently attached to chitosan via a carbodiimide mediated coupling reaction. The resulting chitosan-N-acetyl cysteine conjugate displayed 492 ± 29.6 μmol thiol groups per gram of polymer. In comparison to the native polymer, the conjugate showed an increase in glass transition temperature, improved thermal stability and crystallinity. In vitro mucoadhesive study revealed a 1.45 fold improvement in mucoadhesive force. Acyclovir loaded microspheres of chitosan and chitosan-N-acetyl cysteine were prepared using emulsification crosslinking process with 97.86 ± 2.06% and 76.99 ± 1.14% loading efficiency respectively. In vitro release profile in simulated tear fluid showed initial burst followed by a sustained release for 12 h. Ocular tolerance study in rabbit eye did not reveal any signs and symptoms of ocular toxicity. In conclusion, chitosan-N-acetyl cysteine microspheres represent a promising carrier for ocular administration.

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