Synthesis and characterization of acrylic type hydrogels containing azo derivatives of 5-amino salicylic acid 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. Terephthalic acid was covalently linked with 2-hydroxyethyl methacrylate (HEMA), abbreviated as cross-linking agent (CA). Acryloyl ester of 5-[4-(hydroxy phenyl) azo] salicylic acid (HPAS) as an azo derivative of 5-amino salicylic acid (5-ASA) was prepared under mild conditions. The HPAS was covalently linked with acryloyl chloride, abbreviated as APAS. Free radical cross-linking copolymerization of polymerizable azo derivative of 5-ASA (APAS) and methacrylic acid (MAA) in two different molar ratios, with the various ratios CA as cross-linking agent were carried out with using 2, 2'-azobisisobutyronitrile (AIBN) as initiator at the temperature range 60-70 degrees C. The composition of the cross-linked three-dimensional polymers was determined by FTIR spectroscopy. Glass transition temperature (Tg) 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 degrees C. The effect of copolymer composition on the hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1) and simulated intestinal fluid (SIF, pH 7.4) at 37 degrees C. Monitoring of the hydrolysis process by HPLC and UV spectroscopy shows that the azo prodrug (HPAS) was released by hydrolysis of the ester bond located between the HPAS and the polymer chain. The drug-release profiles indicate that amount drug release dependent on the content of MAA groups and crosslinking.