Clopidogrel loaded nanostructured lipid carrier: Assembly, microstructure and cytotoxicity

Abstract

Here we designed an optimized NLC for the transport of CLP, an antiplatelet molecule, and further probed its microstructure, cytotoxicity and the stability. NLCs were attained through cavitation technology employing RSM-based factorial design (2³). Amount of lipid (X1), ultrasound power (X2), and sonication time (X3) were independent operational variables while Z-Avg (nm), PDI and ZP (mV) were the studied responses. The designed CLP-NLC was scrutinized for DLS, TEM, FESEM, ATR, PXRD, TGA, rheology, drug release and cytotoxicity. An optimized NLC had Z-Avg (217.5 nm), PDI (0.178), and ZP of −36.4 mV. Morphology investigation showed spherical NLCs. ATR analysis demonstrated H-bonding interactions between CLP and Imwitor ensuring drug solubility and holding in the lipid matrix. PXRD confirmed complete drug amorphization during processing pinpointing the influence of capryol (oil) on the formation of lower ordered crystal lattice of Imwitor. Designed NLCs showed dominance of elastic constituent and shear thinning behavior, an anomalous (n > 0.5) type of CLP transport, and an excellent stability over six months. CLP loaded NLC showed significant cellular uptake and marked reduction in cytotoxicity. Thus the ultrasonically designed NLCs can entrap CLP, are biocompatible and safe for the human use, and with the reduced lipid crystallinity modulates the desired drug release.