Synthesis of pH-responsive hydrogel thin films grafted on PCL substrates for protein delivery

A new visible light induced graft polymerization method was utilized to prepare pH-sensitive hydrogel layers covalently attached to polymer substrates for drug delivery. In our strategy, isopropyl thioxanthone semi-pinacol (ITXSP) dormant groups were firstly introduced on the surface of a polycaprolactone (PCL) film by a UV-induced abstracting hydrogen-coupling reaction. Then visible light induced graft cross-linking polymerization was performed to initiate polymerization of poly(ethylene glycol) diacrylate (PEGDA) and acrylic acid (AA), resulting in the formation of a hydrogel layer. The thickness of the hydrogel film can be controlled by varying the exposure time and monomer composition. The grafted hydrogel layers showed a flat morphology and dense structure, which is different from the traditional reported porous structure. The water contact angle of the hydrogel layer exhibited a reversible change from 381 to 181 when the film was alternatively treated in buffers of pH 2.0 and 7.4, respectively. Patterned hydrogel layers were prepared as a model to determine the change in the height of the grafted hydrogel layer as a function of pH. As the pH changed from 2.0 to 7.4, the hydrogel pattern showed an increase in height due to the swelling of the hydrogel network, and the hydrogel layer formed by 0.2 wt% PEGDA and 25 wt% AA showed the most increase (30%) in height. Bovine serum albumin (BSA) and lysozyme as models of protein drugs were incorporated in the hydrogel network, and their release also showed obvious pH-sensitivity. At pH 2.0, hydrogels present a faster initial burst release due to the squeezing mechanism. Tertiary structure analysis showed that encapsulation and release did not affect the protein conformation. These findings have improved our understanding of hydrogel thin films, which may be useful as potential vehicles of therapeutic proteins in drug delivery applications.