Acid degradable poly(vinylcaprolactam)-based nanogels with ketal linkages for drug delivery

Abstract

To improve the biocompatibility and biodegradability of nanocarriers, well-defined poly(vinylcaprolactam)-based acid degradable nanogels were fabricated for drug delivery via precipitation polymerization in water, where synthetic ketal-based 2,2-dimethacroyloxy-1-ethoxypropane (DMAEP) acted as a cross-linker, and N-(2-hydroxypropyl)methacrylamide (HPMA) served as a co-monomer. Expectedly, we observed that the temperature and pH of the environment play important roles in the performance of the nanogels. The nanogels were reduced in size upon increasing the temperature and showed higher volume phase transition temperature (VPTT) with higher concentration of HPMA. With the incorporation of ketal linkages, the nanogels showed accelerated degradation profiles by lowering the pH and increasing temperature of the incubation medium. When used as nanocarriers of anticancer drug doxorubicin (DOX), compared to non-degradable nanogels with similar components, the acid-degradable nanogels displayed more effective drug controlled release behaviour, low drug leakage of DOX at neutral pH while rapid and sufficient release from the nanogels under acidic conditions. The results of the cytotoxicity and hemolysis assays further highlighted that the acid-degradable nanogel produced no hemolysin but showed excellent viability to normal cells, and the DOX-loaded nanogel exhibited higher proliferation inhibition against tumor cells.