Abstract
We have synthesized and studied a new type of polymeric drugcarrier based on hydrophobically modified bioadhesive graft copolymers. Two different hydrophobic oligomers, an oligo(methyl methacrylate) (oMMA) and a random co-oligomer of MMA with hydroxyethyl methacrylate (HEMA) were separately grafted to a polyacrylic acid (PAAc) backbone. This system forms a physical hydrogel network containing hydrophobic domains. The in vitro release of hydrophilic drugs such as theophylline and a model protein drug, lysozyme, and moderately hydrophobic drugs such as propranolol hydrochloride has been investigated. The results suggest the existence of a macroporous structure at higher levels of oMMA grafting. The introduction of HEMA into the graft chain slowed the release of propranolol hydrochloride, which suggests that the release rate of a moderately hydrophobic drug could be controlled by adjusting the hydrophobicity of the grafted chain. In the case of release of lysozyme, a cationic protein used as a model protein drug, the graft copolymers of oMMA retained increasing amounts of the protein as the graft level increased. This supported the concept of formation of a macroporous structure at higher MMA graft levels, with a cationic protein such as lysozyme being attracted to and bound by the hydrophobic domain interfacial regions. The introduction of as little as 10 mol% of HEAIA into the graft chain gave rise to rapid and complete release of lysozyme.
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