PH-sensitive hydrogel containing acetaminophen silyl ethers for colon-specific drug delivery

Abstract

pH-sensitive hydrogels are suitable candidates for oral delivery of therapeutic peptides, proteins and drugs, due to their ability to respond to environmental pH changes. Acetaminophen dimethylvinylsilyl ether was prepared under mild conditions. Cubane-1,4-dicarboxylic acid (CDA) linked to two HEMA groups, giving cubane-1,4-bis(methacryloyloxyethyl) carboxylate (CA), was used as cross-linker. The drug linked to dimethylvinylsilyl was abbreviated as ADVSi. Free radical cross-linking co-polymerization of polymerizable ADVSi with methacrylic acid (MAA) or N-vinyl-2-pyrrolidinone (NVP) with various ratios of CA as cross-linking agent was carried out with using AIBN as initiator in the temperature range 60–70°C. The structure of the ADVSi was confirmed by FT-IR and 1H-NMR spectroscopy. The composition of the cross-linked three-dimensional polymers was determined by FT-IR spectroscopy. The glass transition temperature (T g) of the network polymers was determined calorimetrically. The hydrolysis of drug–polymer conjugates was carried out in cellophane membrane dialysis bags containing aqueous buffer solutions (pH 7.4 and pH 1) at 37°C. The effect of co-polymer composition on the hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 7.4) at 37°C. Detection of the hydrolysis product by UV spectroscopy shows that acetaminophen was released by hydrolysis of the ether bond located between the drug and the polymer chain. The drug-release profiles indicate that the amount of drug released depends on the composition of polymers.