In Vitro Anticancer Drug Delivery Using Amphiphilic Poly(N-vinylpyrrolidone)-b-Polyketal-b-Poly(N-vinylpyrrolidone) Block Copolymer as Micellar Nanocarrier

Abstract

We have first synthesized acid-degradable alkyne-terminated aliphatic polyketal and thereof synthesized novel pH-responsive double hydrophilic amphiphilic block copolymer of poly(N-vinyl pyrrolidone) (PNVP) and aliphatic polyketal (PK) (PNVP-b-PK-b-PNVP via click chemistry upon reaction with azide-terminated PNVP. Formation of block copolymer is confirmed by proton nuclear magnetic resonance, gel permeation chromatography, thermogravimetry, differential scanning calorimetry, and fluorescence spectroscopy techniques. pH-dependent degradation study of the block copolymer shows faster degradation at lower pH. Transmission electron microscopy (TEM) has revealed the formation of tiny (∼3.8 nm) micellar nanoparticles. Loading of the anticancer drugs doxorubicin (Dox) and imatinib in the micelle is confirmed from UV-Visible, and TEM studies. Drug release study from drug-loaded micelles has shown that imatinib is being released faster than Dox and both systems have shown higher load release at acidic pH of 6.4. Doxorubicin- and imatinib- loaded micelles demonstrate significant tumoricidal properties against parental and drug resistant human erythroleukemia K-562 and Dalton's lymphoma cells with respect to enhanced cellular uptake, cytotoxicity and growth inhibition. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim