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

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 (similar to 3.8 nm) micellar nanoparticles. Loading of the anticancer drugs doxor-ubicin (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.