Synthesis and Evaluation of Biocompatible pH-Sensitive Hydrogels as Colon-Specific Drug Delivery Systems

Abstract

Because of the growing importance of pH-sensitive hydrogels as drug delivery systems, biocompatible copolymeric hydrogels based N-vinyl-2-pyrrolidinone (NVP) and methacrylic acid (MAA) were designed and synthesized. These hydrogels were investigated for oral drug delivery. Radical copolymerizations of N-vinyl-2-pyrrolidinone (NVP) and methacrylic acid (MAA) with the various ratios of crosslinking agent were carried out at 70°C. Azabisisobutyronitrile (AIBN) was the free-radical initiator employed and Cubane-1,4-dicarboxylic acid (CDA) linked to two 2-hydroxyethyl methacrylate (HEMA) group was the crosslinking agent (CA) used for hydrogel preparations. The hydrogels were characterized by differential scanning calorimetry and FT-IR. Equilibrium swelling studies were carried out in enzymefree simulated gastric and intestinal fluids (SGF and SIF, respectively). A model drug, olsalazine [3,3¢-azobis (6-hydroxy benzoic acid)] (OSZ) as an azo derivative of 5-aminosalicylic acid (5-ASA), was entrapped in these gels and the in-vitro release profiles were established separately in both enzyme-free SGF and SIF. The drug-release profiles indicated that the amount of drug released depended on the degree of swelling. The swelling was modulated by the amount of crosslinking of the polymer bonded drug (PBDs) prepared. Based on the great difference in hydrolysis rates at pH 1 and 7.4, these pH-sensitive hydrogels appear to be good candidates for colon-specific drug delivery.

Molecular Structure of Physiologically‐Responsive Hydrogels Controls Diffusive Behavior

“…[10–12] Applications of these copolymers have been in industrial settings for water treatment[13] and pervaporation[14] purposes, pharmaceutical settings as protein mimics,[8] and drug delivery purposes in the ocular,[15] oral and colonic[12] delivery of small molecular weight peptides.…”

Cubanes in Medicinal Chemistry

“… Compound 66 has also been developed as a polymerization precursor. Subjecting 66 to free radical copolymerization with various drugs leads to novel and targeted delivery systems. − Nitroxyalkyl groups substituted onto cubane with various linkers have been developed and explored for their anti-ischemic activity (compounds 67 ) . Compound 67a showed an improved ratio between the necrotic and ischemic zones (36.1%) when compared to the lead compound nicorandil ( 68 , 42.0%), where a mononitroxyalkyl is substituted on a pyridine.…”

Release dynamics of ciprofloxacin from swellable nanocarriers of poly(2-hydroxyethyl methacrylate): an in vitro study

“…Two colon-targeting methods-utilization of pH changes within the gastrointestinal tract and exploitation of bacterial enzymes localized within the colon-are of current interest in controlled drug delivery. 22 The wide range of pH allows a specific drug to be delivered to a target site only.…”