Synthesis of poly(HEMA-co-AAm) hydrogels by visible-light photopolymerization of aqueous solutions containing aspirin or ibuprofen: analysis of the initiation mechanism and the drug release

Abstract

Recently, we reported the synthesis of hydrogels by visible-light photopolymerization of 2-hydroxyethylmethacrylate and acrylamide, employing safranine O as sensitizer, and a functionalized silsequioxane (SFMA) as co-initiator/crosslinker. The influence of the ionic character of a drug on its release rate from the hydrogels was also reported. In the present study, we analyzed the photoinitiation mechanism, the synthesis of hydrogels in the presence of aspirin (ASA) or ibuprofen (Ibu), and their release from hydrogels synthesized with variable SFMA concentrations. Concerning the photoinitiation mechanism, we found that the main contribution was the electron transfer reaction between the excited triplet state of safranine and SFMA, followed by a fast proton transfer reaction from secondary amine groups. The generated nitrogen radicals initiated the copolymerization reaction. The photoreaction quantum yield was 0.031. Concerning the drug-release study, we found that the release rate of both drugs increased by increasing pH from 7 to 10. This was ascribed to the increase in the partial ionization of the carboxylic acid groups, a fact that reduced the interactions with the secondary amine groups present in SFMA and increased the release rate. The effect was larger for ASA than for Ibu. Increasing the amount of SFMA increased both the crosslink density and the fraction of H-bonds formed with the drugs. At pH 10, the increment in the crosslink density was dominant for the release of Ibu while the increase in fraction of H-bonds determined the release rate of ASA. Cytotoxicity studies showed that these materials did not exhibit significant hemolytic activity.