Synthesis and properties of non‐cytotoxic poly(l‐malic acid acetate‐co‐l‐lysine ester)s with thermo‐sensitivity as hydrophobic drug nanocarrier

In this investigation, a group of poly(l ‐malic acid acetate‐co‐l ‐lysine ester)s (PMALs) with excellent thermo‐sensitivity and non‐cytotoxicity were prepared by an optimized synthetic route from natural l ‐malic acid and l ‐lysine. The structure and properties of PMALs including monomers were systematically characterized by FTIR, ¹H NMR, UV, gel permeation chromatograph, scanning electron microscope, contact angle measurement, cell counting kit assess (CCK‐8), and confocal laser scanning microscopy (CLSM). Three PMALs show a reversible lower critical solution temperature of 8–36 °C depending on their chemical structure. The contact angle measurement revealed a considerable discrepancy in the hydrophilicity/hydrophobicity of PMALs and further influence on their thermo‐sensitivity. The viability of HeLa cells exposed to 0.2–100 μg/mL PMALs solution was found to be in a range 80–103% after 24, 48, and 72 h of incubation, indicating no cytotoxicity. Moreover, a spherical nanocarrier with core‐shell structure was facilely fabricated via the thermo‐sensitivity of PMALs and hydrophobicity of drug. CLSM observations manifested that the hydrophobic‐curcumin‐enwrapped nanocarriers can clearly internalize into the cellular inside. The sustained release of curcumin from nanocarriers in vitro provided a possibility of depressing fast hydrolytic degradation at physiological pH or other side‐effects. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45984.