(647g) P?G-Based Nanocomposite Hydrogels: Thermoresponsive Sol-Gel Transitions and Decomposition Rates Regulated By the L?/GA Ratio of PLGA-P?G-PLGA

Our group developed a nanocomposite made of PLGA-PEG-PLGA (poly (_D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (_D,L-lactide-co-glycolide)) and laponite-clay nanoparticles (laponite/PLGA-PEG-PLGA nanocomposites), exhibiting thermoresponsive sol-gel transitions and biodegradability [1, 2]. The laponite/PLGA-PEG-PLGA nanocomposites could exhibit higher biocompatibility by their high PEG/PLGA ratio, and the higher drug-encapsulation efficiency by the low solute concentration. To establish an efficient laponite/PLGA-PEG-PLGA nanocomposite as a material for the drug-delivery system (DDS), the decomposition rate of the laponite/PLGA-PEG-PLGA nanocomposite should be properly controlled. In this study, the thermoresponsive sol-gel transition and the decomposition rate of the laponite/PLGA-PEG-PLGA nanocomposites were optimized by varying the LA/GA ratios (LA/GA=1.1, 4.0, 8.8) in the PLGA parts of the PLGA-PEG-PLGA with the constant molecular weights of 600-1000-600, respectively. The sol-gel transition temperatures were found to be in the temperature range between 25°C and 37°C regardless of the LA/GA ratios when the polymer concentration was 4 wt% and the laponite concentration was 0.75 wt%. In fact, the sol-gel transition temperatures were 34°C for LA/GA=1.0, 35°C for LA/GA=4.0, and 35°C for LA/GA=8.8. As for the decomposition of the gels at 37°C, the laponite/PLGA-PEG-PLGA nanocomposite gels with the LA/GA=4.0 and the LA/GA=8.8 both showed ~30% of the mass loss after 10 days, while the laponite/PLGA-PEG-PLGA nanocomposite gels of LA/GA=1.1 showed ~45% of the mass loss after 10 days. Additionally, the protein release from the gel was also examined as a preliminary test for the DDS application. The results revealed the highly versatile features of the aqueous laponite/PLGAPEG-PLGA nanocomposites with prospective thermoresponsive sol-gel transitions and with finely-controlled decomposition behavior especially for the DDS application.

[1] Naho Oyama, Hiromasa Minami, Daichi Kawano, Makoto Miyazaki, Tomoki Maeda, Kazunori Toma, Atsushi Hotta, Koji Nagahama, A nanocomposite approach to develop biodegradable thermogels exhibiting excellent cell-compatibility for injectable cell delivery, Biomaterials Science, Vol.2 (8), 1057-1062 (2014).

[2] Makoto Miyazaki, Tomoki Maeda, Kenji Hirashima, Naruki Kurokawa, Koji Nagahama, Atsushi Hotta, PEG-based nanocomposite hydrogel: Thermoresponsive sol-gel transition controlled by PLGA-PEG-PLGA molecular weight and solute concentration, Polymer, Vol.115, 246-254 (2017).