Biodegradable thermo-sensitive nanoparticles from poly(l-lactic acid)/poly(ethylene glycol) alternating multi-block copolymer for potential anti-cancer drug carrier.

摘要

In order to produce biodegradable thermo-sensitive nanoparticles, alternating multi-block copolymers (MBC) were synthesized by coupling dicarboxylated poly(ethylene glycol) (PEG; M(w) 2000) with poly(l-lactic acid) (PLLA)/PEG/PLLA triblock copolymers. Three different multi-block copolymers were synthesized by varying PLLA molecular weight (800 (MBC1), 1600 (MBC2), and 2800 (MBC3)). The MBC formed self-assembled nanoparticles with a unimodal size distribution during a dialysis process. The nanoparticles (NP) had a spherical shape with a size range of 90-330nm in diameter and critical aggregation concentrations in a range of 5.6-12.6mug/mL, depending on PLLA length in MBC. The thermo-sensitivity of MBC NP was monitored by the changes in particle size and interior structure as a function of temperature. The particle size slightly decreased as increasing temperature from 37 to 42 degrees C. The interior structure of the NP responded to temperature by altering microviscosity. The microviscosity, measured bythe anisotropy (r value) of a fluorescence probe, of MBC1 NP significantly changed with increasing temperature (r=0.187 at 25 degrees C and 0.216 at 42 degrees C), while MBC2 and MBC3 showed negligible changes in the microviscosity. This indicates that the temperature-dependent interior structure of the NP relied on the portion of PLLA in MBC. The thermo-sensitivity affected to the drug release behavior and cell cytotoxicity. At 42 degrees C, doxorubicin (DOX) loaded MBC1 NP showed enhanced cytotoxicity ( approximately 20 times) against Lewis Lung Carcinoma (LLC) cells when compared to that at 37 degrees C.