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 X1
(Polymer concentration), X2 (pH), and X3 (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.