(196k) Decomposition Behavior of Laponite/PLGA-P?G-PLGA Nanocomposite Hydrogels at Body Temperature

PLGA-PEG-PLGA (poly (_D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (_D,L-lactide-co-glycolide)) is one of the promising block-copolymers exhibiting interesting thermoresponsive sol-gel transitions and biodegradability. We have developed thermoresponsive hydrogels using PLGA-PEG-PLGA possessing a high PEG/PLGA ratio with laponite clay nanoparticles (laponite/PLGA-PEG-PLGA nanocomposites) for the drug delivery system (DDS) [1, 2]. The laponite/PLGA-PEG-PLGA nanocomposites presented a thermoresponsive sol-gel transition at the total solute concentration of 3.75 wt%, while the PLGA-PEG-PLGA single-body solution presented a sol-gel transition at the solution concentration of 15 wt% or higher at body temperature (37°C). To adjust the degradation rate for the control of the drug-release rate in the DDS, the decomposition behavior should be studied comprehensively. In this work, the decomposition behavior including the decomposition rate was investigated for the laponite/PLGA-PEG-PLGA nanocomposite hydrogels. The PLGA-PEG-PLGA triblock copolymers of the same molecular weight (600-1000-600) but with different LA/GA ratios (1.1, 4.0, and 8.8) were used for the experiments. The decomposition behavior was examined by analyzing the mass loss of the nanocomposites and by analyzing the composition of the remaining gels by NMR. The mass losses of the laponite/PLGA-PEG-PLGA nanocomposite gels with the LA/GA ratio of 4.0 and the LA/GA ratio of 8.8 were ~30% after 10 days for both samples, while the mass loss of the laponite/PLGA-PEG-PLGA nanocomposite gels with the LA/GA ratio of 1.1 was ~45% after 10 days. From the analyses by the NMR spectra, it was found that there was an increase in the LA content, a decrease in the PEG content, with no remarkable change in the GA content, regardless of the LA/GA ratios. Thus it was considered that more hydrophilic PEG blocks were preferentially diffused out of the nanocomposite gel during the decomposition, and that LA and GA remained in the nanocomposite hydrogels. If we consider the composition change of the nanocomposite hydrogels analyzed by NMR as the decomposition rate, the decomposition rate of the nanocomposite hydrogels with LA/GA=1.1 was higher than those with LA/GA=4.0 and LA/GA=8.8.

[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).