Non-cytotoxic poly(amino acid) with excellent thermo-sensitivity from L-lysine and L-aspartic acid as a hydrophobic drug carrier

Abstract

The thermo-sensitive poly(amino acid)s have aroused great concern due to their good biocompatibility, chirality and multi-functional groups. In this investigation, a group of poly(L-lysine ester -co- N-propionyl-L-aspartic acid)s (PLPA) with excellent thermo-sensitivity and non-cytotoxicity have been successfully synthesized by the polycondensation between α/e-amino groups of L-lysine and α/γ-carboxyls from L-aspartic acid. The structure and properties of PLPA including monomers are characterized by FTIR, 1H NMR, UV, DSC, GPC, SEM, Contact angle measurement, CCK-8 Cell Counting Kit assess and Confocal laser-scanning microscopy (CLSM). Among four designed PLPAs, only PLPAs possessing methyl/ethyl in the ester moiety show a reversible lower critical solution temperature (LCST) of 21.3–36.2 °C, very close to body temperature. The thermo-sensitivity of PLPAs is strongly affected by the polymer structure, its molecular weight and concentration. The contact angle measurement clearly reveals the effect of pendant groups and temperature on the hydrophlilicity/hydrophobicity of PLPAs. Furthermore, the viability of HeLa cells in 0.01–100 μg/mL PLPA solution is found to be in a range of 90–102% after 24, 48 and 72 h of incubation, indicating its no cytotoxicity. PLPA can facilely form a spherical nano-scale particle with core-shell structure via its thermo-sensitivity. CLSM observations manifest that the curcumin-loaded PLPA particles clearly internalize into the cellular inside. Overall, this noncytotoxic PLPA with excellent thermo-sensitivity is expected to be a promising material in the biomedical fields such as a hydrophobic drug carrier.