POLYMERIC NANOPARTICLES AS POTENTIAL CARRIERS FOR TOPICAL DELIVERY OF COLCHICINE: DEVELOPMENT AND IN VITRO CHARACTERIZATION

The aim of the present study is to develop a nanoparticle formulation as a potential carrier for topical drug delivery. Colchicine loaded Nanoparticles (Colchicine-NPs) were prepared by the double emulsion solvent evaporation method using biodegradable and non biodegradable polymers alone or as binary mixtures. Based on the evaluation of the entrapment efficiency, the particle size and the % drug released over 24 hours, a polymer mixture of poly-D,L-lactic acid (PLA), and Eudragit RL, in the weight ratio 1:1 was selected for further studies. The following formulation variables were optimized: the pH of the external aqueous phase was adjusted to a value of pH 6 in order to decrease the solubility of colchicines; the solvent composed of dichloromethane and acetone 1:1 (v/v) was selected to obtain maximum  water miscibility;  CaCl₂ was selected as a counter ion additive in the external aqueous phase; Span was used in the internal organic phase to increase entrapment efficiency and medium chain triglyceride was found to be most efficient at a concentration of 30% w/w. As a result of the optimization, the entrapment efficiency attained a maximum value of 44.6 %, the particle size was in the nanometer range and the zeta potential varied from 31.1 mV to 45 mV indicating good stability. The NPs were almost spherical with smooth morphology. The release profile of the optimized formulations was characterized by a burst release in the first 8 h followed by a sustained release up to 24 h. The cumulative percentage released after 24 h was between 15-16 %.