Bioavailability and Antidiabetic Activity of Gliclazide-Loaded Cubosomal Nanoparticles.

Mohamed Nasr,Alaa Y Bazeed,Sameh Saber,Heba I Elagamy,Ahmed Al Saqr,Saud Almawash

doi:10.3390/ph14080786

Abstract

In this study, gliclazide-loaded cubosomal particles were prepared for improving the oral bioavailability and antidiabetic activity of gliclazide. Four formulations of gliclazide-loaded cubosomal nanoparticles dispersions were prepared by the emulsification method using four different concentrations of glyceryl monooleate (GMO) and poloxamer 407 (P407) as the stabilizer. The prepared formulations were in vitro and in vivo evaluated. In vitro, the prepared gliclazide-loaded cubosomal dispersions exhibited disaggregated regular poly-angular particles with a nanometer-sized particle range from 220.60 ± 1.39 to 234.00 ± 2.90 nm and entrapped 73.84 ± 3.03 to 88.81 ± 0.94 of gliclazide. In vitro gliclazide release from cubosomal nanoparticles revealed an initially higher drug release during the first 2 h in acidic pH medium; subsequently, a comparatively higher drug release in alkaline medium relative to gliclazide suspension was observed. An in vivo absorption study in rats revealed a two-fold increase in the bioavailability of gliclazide cubosomal formulation relative to plain gliclazide suspension. Moreover, the study of in vivo hypoglycemic activity indicated that a higher percentage reduction in glucose level was observed after the administration of gliclazide cubosomal nanoparticles to rats. In conclusion, gliclazide-loaded cubosomal nanoparticles could be a promising delivery system for improving the oral absorption and antidiabetic activity of gliclazide.

Highlights

Gliclazide, a second-generation sulfonylurea, is an effective oral hypoglycemic drug adopted to treat non-insulin-dependent diabetes mellitus
The obtained mean particle sizes of cubosomal nanoparticles ranged from 220.60 ± 1.39 to 234.00 ± 2.90 nm
There were no significant differences between particle sizes of all formulas; a slight increase in the particles size was associated with increasing Glyceryl monooleate (GMO) concentration from 1.25 to 7.50% w/w

Summary

Introduction

Gliclazide, a second-generation sulfonylurea, is an effective oral hypoglycemic drug adopted to treat non-insulin-dependent diabetes mellitus. Due to its low and pH-dependent solubility [4,5], gliclazide has an irregular and slow absorption rate which can result in large intra- and inter-individual changes in absorption following oral administration [6,7]. Several formulation techniques have been adapted to improve the bioavailability and therapeutic effectiveness of gliclazide such as the preparation of solid dispersion [8,9], inclusion complex with β-cyclodextrin [10], nanocrystals [11], liquid–solid systems [12], solid lipid nanoparticles [13], and self-micro-emulsifying delivery system [14]. The previously mentioned approaches rely on increasing the solubility of gliclazide as a mechanism for Pharmaceuticals 2021, 14, 786.

Methods

Results

Conclusion