Clopidogrel Loaded Albumin Nanoparticles for the Management of Atherosclerosis: Preparation and Optimization by Box-Behnken Design

This study aimed to formulate and optimize the clopidogrel loaded bovine serum albumin nanoparticles as a sustained drug delivery system for effective management of atherosclerosis. The antiplatelet drug clopidogrel has poor water solubility and oral availability of <= 50% with rapid first -pass metabolism. The clopidogrel loaded albumin nanoparticles were successfully prepared by the desolvation technique and the Box-Behnken quadratic model which was employed for optimization. For the initial study, the concentration of BSA, 4% v/v glutaraldehyde, and the pH of the polymeric solution were modified and the stirring speed, stirring time, and quantity of drug were kept constant. The process yield, PDI and drug loading were characterized. As the preliminary formulation had higher PDI, particle size and lower drug loading, the formulation was further subjected to optimization by Box-Behnken design. The Box-Behnken quadratic model was employed to optimize the formulation and to study the effect of independent variables like X 1 (Polymer concentration), X 2 (pH), and X 3 (Cross -linking hours) on dependent variables like particle size, PDI, and drug loading. The particle morphologies and zeta potential of optimized CLP-BSA NPs were examined. The efficiency of nanoparticles was confirmed in the Wister albino rats, and the animals treated with CLP-BSA NPs showed prolonged clotting and bleeding time compared to control and clopidogrel drug solution -treated groups.