Chitosan Nanoparticles for Prolonged Delivery of Timolol Maleate

Abstract

Timolol maleate-loaded chitosan (CS) nanoparticles were prepared by desolvation method. Experimental variables such as molecular weight of CS and amount of crosslinking agent were varied to study their effect on drug entrapment efficiency, size and release rates of nanoparticles. Chemical stability of timolol maleate (TM) and crosslinking of CS were confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetric studies were performed on drug-loaded nanoparticles to investigate crystalline nature of the drug after entrapment. Results indicated amorphous dispersion of drug in the polymer matrix. Scanning electron microscopy revealed irregularly shaped particles. Mean particle size of nanoparticles ranged between 118 and 203 nm, while zeta potential ranged between +17 and +22 mV. Entrapment efficiency of nanoparticles ranged between 47.6 and 63.0%. In-vitro release studies were performed in phosphate buffer saline of pH 7.4. A slow release of TM up to 24 h was observed. A 3(2) full factorial design was employed and second-order regression models were used to study the response (% drug release at 4 h). Release data as analyzed by an empirical relationship suggested that drug release deviated from the Fickian trend.