Preparation, optimization, and characterization of chitosan-coated solid lipid nanoparticles for ocular drug delivery.

Wang Fengzhen,Chen Li,Zhang Dongsheng,Jiang Sunmin,Zhang Mingwan,Li Rui,Shi Kun,Huang Yuan

doi:10.7555/jbr.32.20160170

Abstract

The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles (chitosan-SLNs) encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsification-solvent evaporation method with glyceryl monostearate as the solid lipid and phospholipid as the surfactant. Systematic screening of formulation factors was carried out. The optimized formula for preparation was screened by orthogonal design as well as Box-Behnken design with entrapment efficiency, particle size and zeta potential as the indexes. The entrapment efficiency of the optimized formulation (methazolamide-chitosan-SLNs) prepared was (58.5±4.5)%, particle size (247.7±17.3) nm and zeta potential (33.5±3.9) mV. Transmission electron microscopy showed homogeneous spherical particles in the nanometer range. A prolonged methazolamide in vitro release profile was obtained in the optimized chitosan-SLNs suspension compared with methazolamide solution. No ocular damages were observed in the susceptibility test on albino rabbits. The results suggest that the combination of orthogonal design and Box-Behnken design is efficient and reliable in the optimization of nanocarriers, and chitosan-SLNs is a potential carrier for ophthalmic administration.

Highlights

Solid lipid nanoparticles (SLNs) are a novel colloidal drug delivery system with an inner structure based on solid lipids
During the preparation of chitosan-associated SLNs loaded with methazolamide, we found that phospholipid or glyceryl monostearate (GMS) amount and chitosan concentration could influence the physicochemical properties of methazolamide-chitosan-SLNs
The influence of the independents on the weighted sum of the dependents is in the following order: C (GMS) > B > E > D > A, based on R values (Table 4), which suggests that C, B, E are three significant factors

Summary

Introduction

Solid lipid nanoparticles (SLNs) are a novel colloidal drug delivery system with an inner structure based on solid lipids. It derives from oil-in-water (o/w) emulsion with lipids that are solid at ambient temperature. This desirable drug carrier system demonstrates advantages such as good biocompatibility, low toxicity, drug release modulation, and the possibility of established mass production[1–3]. Our previous studies demonstrated that SLNs incorporating methazolamide could desirably decrease the intraocular pressure (IOP) of rabbit eyes upon topical application for glaucoma[4]. Its poor corneal permeability became a major challenge as negatively charged SLNs could hardly interact with negatively charged corneal surface.

Methods

Results

Conclusion