Temperature-Sensitive Poly(vinyl alcohol)/Poly(methacrylate-co-N-isopropyl acrylamide) Microgels for Doxorubicin Delivery

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Abstract
Microgels based on poly(vinyl alcohol), PVA, grafted with methacrylate side chains, MA, incorporating N-isopropylacrylamide, NiPAAm, monomer, were prepared by water-in-water emulsion polymerization method. These systems exhibit a spherical shape and a volume-phase transition, that is, shrinking, below physiological temperature. The behavior of these microgels were studied with respect to their average size and size distribution, swelling, and release properties. It was observed that the stirring speed is a key parameter for controlling the amount of incorporated NiPAAm, the particle size and the sharpness of the volume-phase transition. The volume-phase transition temperature, VPPT, of the microgels was evaluated around 38 and 34 °C for microgels with a NiPAAm/methacrylate molar ratio of 0.8 and 2.4, respectively. Water uptake increased with the amount of NiPAAm monomer present in the polymer network. In vitro biocompatibility of microgels was assessed with respect to NIH3T3 mouse fibroblasts. O-Succinoylated microgels were loaded with doxorubicin by exploiting the favorable electrostatic interaction between negatively charged microgel surface and positively charged doxorubicin. The drug release was influenced by the microgels surface/volume ratio. At physiological temperatures, above the VPTT exhibited by these systems, the release was enhanced by the specific area increase. This study provides the background for the design of an injectable device suitable for the controlled delivery of doxorubicin based on the volume-phase transition of microgels.

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