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A Hydrophobically Modified Bioadhesive Polymeric Carrier for Controlled Drug Delivery to Mucosal Surfaces

Center for Bioengineering Box 352255, University of Washington, Seattle, WA 98195

Guohua Chen

Center for Bioengineering Box 352255, University of Washington, Seattle, WA 98195

Allan S. Hoffman

Center for Bioengineering Box 352255, University of Washington, Seattle, WA 98195

Katsuhiko Nakamae

Faculty of Engineering, Kobe University, Rokko, Nada, Kobe 657, Japan

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.

Journal of Bioactive and Compatible Polymers, Vol. 13, No. 1, 50-64 (1998)
DOI: 10.1177/088391159801300105


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