title: Mucoadhesive nanoparticles for prolonged ocular delivery of natamycin: In vitro and pharmacokinetics studies.
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.
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, 226001, India. rabi.cdri@gmail.com
authors.forename: R S
authors.initials: RS
authors.lastname: Bhatta
authors.forename: H
authors.initials: H
authors.lastname: Chandasana
authors.forename: Y S
authors.initials: YS
authors.lastname: Chhonker
authors.forename: C
authors.initials: C
authors.lastname: Rathi
authors.forename: D
authors.initials: D
authors.lastname: Kumar
authors.forename: K
authors.initials: K
authors.lastname: Mitra
authors.forename: P K
authors.initials: PK
authors.lastname: Shukla
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D054709:Lecithins / Q000737:chemistry; D008297:Male; D008826:Microbial Sensitivity Tests; D009077:Mucins / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010866:Natamycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D011817:Rabbits
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D054709:Lecithins; D009077:Mucins; D010866:Natamycin; D048271:Chitosan