Development of a Thermally Responsive Nanogel Based on Chitosan–Poly(N-Isopropylacrylamide-co-Acrylamide) for Paclitaxel Delivery

ABSTRACT A thermally responsive nanogel was developed through the radical polymerization based on chitosan (CTS) and N-isopropylacrylamide (NIPAAm) with acrylamide (AAm) blended to explore the possibility of increasing the volume phase transition temperature (VPTT). The thermally sensitive features of resultant nanogels were studied by determining variance of transmittance and changeable size. The VPTT of the CTS–poly(NIPAAm-co-AAm5.5) nanogel, coplymerized with 5.5% wt. AAm /wt. NIPAAm, was 38°C in contrast to 32°C of the CTS–poly(NIPAAm) polymer and the former was studied thereafter. The critical aggregation concentration of CTS–poly(NIPAAm-co-AAm5.5) nanogels was 1.11 μg/mL, much smaller than CTS–poly(NIPAAm) nanogels (5.00 μg/mL). Paclitaxel (PTX) was encapsulated in CTS–poly(NIPAAm-co-AAm5.5) nanogels with loading efficiency of about 9.06 ± 0.195% ( n = 3). Thermally responsive PTX in vitro release fromPTX-loaded nanogels was verified. Coumarin-6-loaded nanogels showed thermally responsive cellular uptake because of electrostatic absorptive endocytosis. Furthermore, the half maximal inhibitory concentration of PTX-loaded nanogels was about 2.025 nmol/L, 10-fold improved relative to PTX solutions against SMMC 7721 cells. In vivo , PTX-loaded nanogels presented remarkably higher antitumor efficacy against human colon carcinoma cells HT-29 xenograft nude mice model after intravenous administration. Accordingly, our results reinforced the potential means of CTS–poly(NIPAA m -co-AAm5.5) nanogels for the combination of thermal therapy and chemotherapy.