A novel thermosensitive polymer with pH-dependent degradation for drug delivery.

A class of thermosensitive biodegradable multiblock copolymers with acid-labile acetal linkages were synthesized from Pluronic triblock copolymers (Pluronic P85 and P104) and di-(ethylene glycol) divinyl ether. The novel polymers were engineered to form thermogels at body temperature and degrade in an acidic environment. The Pluronic-based acid-labile polymers were characterized using nuclear magnetic resonance, gel permeation chromatography and differential scanning calorimetry. In vitro biocompatibility of the synthesized polymers was evaluated using calorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The polymers showed reverse thermogelling behavior in water around body temperature. The sol-gel transition temperatures of the polymers synthesized from Pluronic P85 and P104 were lowered from 70.3 to 30 degrees C and from 68.5 to 26.9 degrees C, respectively, when the synthesized polymers were compared with corresponding Pluronic block copolymers at a concentration of 25wt.%. The hydrophobic dye solubilization confirmed the formation of polymeric micelles in the aqueous solution. The sizes of the multiblock copolymers increased on a rise in temperature, indicating that thermal gelation was mediated by micellar aggregation. The thermally driven hydrogels showed preferential polymer degradation at acidic pH. At pH 5.0 and 6.5, the release of 40kDa fluorescein isothiocyanate-dextran (FITC-dextran) from the thermally formed hydrogels was completed within 2 and 9 days, respectively. However, FITC-dextran was continuously released up to 30 days at neutral pH. The mechanism of FITC-dextran release at pH 5.0 was mainly an acid-catalyzed degradation, whereas both diffusion and pH-dependent degradation resulted in FITC-dextran release at pH 6.5. The novel polymers hold great potential as a pH-sensitive controlled drug delivery system owing to their interesting phase transition behavior and biocompatibility.