Optimization and Characterization of Gentamicin Loaded Chitosan Microspheres for Effective Wound Healing

Abstract:

In the present study, Box-Behnken experimental design was employed to statistically optimize the formulation parameters of gentamicin sulphate loaded chitosan microspheres for maximum entrapment and controlled release. The independent variables selected were concentration of drug (X₁), cross linking agent (X₂) and chitosan 1 2 concentration (X₃) whereas dependent variables studied were entrapment efficiency (Y₁) and mean diameter (Y₂) of 3 1 2 microspheres. The quantitative effect of the formulation parameters at different levels on drug entrapment and microsphere size could be predicted using polynomial equations. For estimation of coefficients in the approximating polynomial function, the least square regression method was applied. The information about the model reliability was verified by using the analysis of variance (ANOVA). A formulation comprising of 10mg gentamicin, 2% (w/v) tripolyphosphate and 3% (w/v) chitosan, was identified for maximizing entrapment (80.04±2.24%) and minimizing particle size to optimum level (18.64±0.61μm). The optimal microsphere preparation was subsequently characterized in terms of morphology, release kinetics, and antimicrobial activity. Scanning electron microscopy confirmed the smooth spherical microspheres in the size range of 11.42±0.56μm to 26.34±0.72μm. Kinetic models revealed that drug release followed non-Fickian pattern. Drug bioactivity was found to remain intact after microencapsulation. Thus, experimental design methodology could efficiently be applied for characterization and optimization of parameters affecting drug entrapment to obtain the maximum amount of information in a short period of time with the fewest number of experiments.

Keywords: Gentamicin, chitosan, Box-Behnken Design, Microspheres