Mucoadhesive nanoparticles for prolonged ocular delivery of natamycin: In vitro and pharmacokinetics studies

Int J Pharm. 2012 Aug 1;432(1-2):105-12. doi: 10.1016/j.ijpharm.2012.04.060. Epub 2012 Apr 28.

Abstract

The aim of this study was to prepare natamycin encapsulated lecithin/chitosan mucoadhesive nanoparticles (NPs) for prolonged ocular application. These NPs were characterized by their mean particle size 213nm, encapsulation efficiency 73.57%, with a theoretical drug loading 5.09% and zeta potential +43. In vitro release exhibited a biphasic drug release profile with initial burst followed by a very slow drug release. The MIC(90) and zone of inhibition of NPs showed similar antifungal activity as compared to marketed suspension and free natamycin against Candida albicans and Aspergillus fumigates. The ocular pharmacokinetics of NPs and marketed formulation were evaluated in NZ rabbits. The NPs exhibit significant mucin adhesion. The AUC((0-∞)) was increased up to 1.47 fold and clearance was decreased up to 7.4-fold as compared to marketed suspension. The PK-PD and pharmacokinetic simulation was carried out to estimate optimum dosing regimen for good efficacy. Thus, lecithin/chitosan NPs could be considered useful approach aiming to prolong ocular residence and reduce dosing frequency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Animals
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / pharmacokinetics
  • Aspergillus fumigatus / drug effects
  • Candida albicans / drug effects
  • Chitosan / chemistry
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics
  • Lecithins / chemistry
  • Male
  • Microbial Sensitivity Tests
  • Mucins / chemistry
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Natamycin / administration & dosage*
  • Natamycin / pharmacokinetics
  • Particle Size
  • Rabbits

Substances

  • Antifungal Agents
  • Drug Carriers
  • Lecithins
  • Mucins
  • Natamycin
  • Chitosan