Efficient delivery of hydrophobic drug, Cabazitaxel, using Nanodisc: A nano sized free standing planar lipid bilayer

Abstract

Several new drug candidates have emerged as potential cancer therapeutics with the advent of drug discovery. The hydrophilic drug candidates have easily translated to chemotherapy via oral or intravenous administration methods, whereas efficient drug delivery vehicles for hydrophobic drugs have been an area of concern. This has resulted in an increasing interest in the nano-sized polymer and lipid-based drug delivery systems due to their enhanced distribution, bioavailability, and therapeutic value. In this study, the efficiency of membrane scaffold protein (MSP) embedded POPC (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine) nanodiscs has been investigated as a hydrophobic drug delivery vehicle. Synthesized nanodiscs with an average diameter of 27.03 ± 1.5 nm were loaded with different hydrophobic drugs and evaluated for biocompatibility and drug release kinetics. The drug loading was found to be proportional to the hydrophobicity (LogP) of the drugs. Drug loaded nanodiscs showed sustained drug release till 24 h which was preceded by initial burst release. Drug delivery efficacy of cabazitaxel loaded nanodiscs (NDCBT) was tested by in vitro cytotoxicity assay, cell cycle arrest analysis, and spheroid growth inhibition study. We achieved significant enhancement of autophagy mediated cell death using NDCBTs when compared to free drug. Similarly, NDCBTs were able to induce approximately 20% higher toxicity in 3D spheroids model.