Synthesis and characterization of grafted thermosensitive hydrogels for heating activated controlled release

Poly(N-isopropylacrylamide), PNIPAAm, hydrogels are negatively thermosensitive which means that they have an expanded hydrogel structure at low temperatures and a shrunken structure at high temperatures. Based on this negative thermosensitivity of PNIPAAm, a drug delivery system with PNIPAAm oligomers grafted onto poly(hydroxyethyl methacrylate) PHEMA, a thermally nonresponsive polymer was designed. Poly(hydroxyethyl methacrylate-g-N-isopropylacrylamide), P(HEMA-g-NIPAAm) hydrogels were synthesized to control the release of an imbedded drug. This new grafted system exhibited high diffusivity at temperatures greater than the lower critical solution temperature (LCST) of the PNIPAAm oligomers. Utilizing PNIPAAm's LCST of approximately 34 degrees C, the release rate was controlled by the temperature of the release medium. The LCST of PNIPAAm was tuned by making copolymers with hydrophobic butyl methacrylate (BMA). Theophylline and inulin release profiles were studied using PHEMA, PNIPAAm and P(HEMA-g-NIPAAm) at three temperatures with drug diffusion coefficients determined as a function of temperature and drug type. The molecular weights between crosslinks and mesh sizes of PHEMA hydrogels were calculated using Flory-Rehner and rubber-elasticity theories. (C) 2006 Elsevier B.V. All rights reserved.