Preparation and Characterization of Novel Amphiphilic Hydrogels with Covalently Attached Drugs and Fluorescent Markers

Abstract

This paper describes the synthesis of styrene-based macromonomers with covalently attached model drugs (ibuprofen and naproxen) or fluorescent markers (pyrene) and their incorporation into linear or hyperbranched p-(chloromethyl)styrene copolymers. Alternatively the copolymers were produced by postpolymerization modification of linear or hyperbranched poly[p-(chloromethyl)styrene], PPCMSt, with the same compounds. The incorporation of these copolymers into amphiphilic conetworks was achieved by two methods: Williamson ether synthesis between PPCMSt and poly(ethylene glycol), PEG, with hydroxyl end groups or by nucleophilic substitution between the chloromethyl moieties in PPCMSt and the amine end groups in poly(oxyalkylenediamine), Jeffamine. The dynamic and equilibrium swelling properties were studied on representative Jeffamine hydrogels. The swelling studies showed that the conetworks absorb water quickly and reach equilibrium in 1−2 h, the equilibrium swelling ratio of gels based on linear or hyperbranched copolymer being 181−358% and 244−480%, respectively. Preliminary drug release studies in different aqueous media showed that the release kinetics and the amount of drugs released from hydrogels depend on the physical properties of drugs, the microstructure of polymer network, and the drug−polymer interaction and more particularly on the hydrolysis dynamics of ester linkage between the drug and the polymer matrix.