A hydrophobically-modified bioadhesive polyelectrolyte hydrogel for drug delivery

Abstract

A hydrophobically-modified bioadhesive polyelectrolyte hydrogel has been prepared by grafting oligomers of methyl methacrylate (MMA) to the backbone of a poly(acrylic acid) (PAAc) hydrogel. Swelling behaviour and drug release profiles of the hydrogel have been studied for six model drugs. The higher the graft level of the oMMA, the slower the swelling as well as the lower the extent of swelling, probably due to the higher concentration of hydrophobic grafts and their aggregation into domains within the hydrogel. The drug release profile from the hydrogels was investigated using phosphate buffered saline (PBS) as a release medium. In the case of hydrophilic drugs, such as theophylline, the drug release rate was enhanced by the oMMA modification. The formation of hydrophobic domains might enlarge the aqueous pore sizes of the hydrogel, thus permitting the hydrophilic drug to diffuse out more rapidly. On the contrary, for moderately hydrophobic drugs such as propranolol hydrochloride, the release rate was slowed down by the oMMA modification. This is probably due to favoured absorption of the hydrophobic groups of the drug into the oMMA domains and the lack of interconnections between the domains. Our results also suggest that ionic interaction of the cationic drug, propranolol hydrochloride, with the network is fairly weak and that hydrophobic interactions seem to be the major force for loading propranolol hydrochloride in the hydrogel. In the case of a positively charged protein, such as lysozyme, the higher the graft level of the OMMA, the slower the release. In addition to its ionic interaction with the PAAc, lysozyme seems also to interact with the hydrophobic domains which can slow or even limit its ionic exchange-driven release mechanism. The hydrophobically-modified bioadhesive hydrogel could be useful for sustained release of hydrophobic drugs or oppositely-charged proteins.