Chitosan-5-aminosalicylic acid conjugates for colon-specific drug delivery: Methods of preparation and in vitro evaluations

Abstract Increasing the efficiency and specificity of drug delivery to the colon is recognized as advantageous for improving the treatment of inflammatory bowel diseases. Novel colon-specific delivery systems for 5-aminosalicylic acid (5-ASA) were developed by conjugating the active to chitosan as a drug carrier via a 4-aminobenzoyl spacer. Chitosan-5-ASA azoconjugates were synthesized from N-(4-aminobenzoyl)-chitosan by diazotization reaction with salicylic acid producing a 55–66% yield. FT-IR and UV–visible spectroscopy confirmed that the chitosan-5ASA azoconjugates were stable and did not release 5-ASA in simulated gastric fluid (SGF, hydrochloric acid pH 1.2), simulated intestinal fluid (SIF, phosphate buffer pH 6.8) and simulated colon fluid (SCF, phosphate buffer pH 7.4) for 24 h at 37 °C. The release of 5-ASA from the chitosan-5-ASA azoconjugates in SGF, SIF and SCF containing rat gastrointestinal contents was determined using HPLC and compared with 5-ASA release from sulfasalazine which employs sulfapyridine as the azoreductable carrier. Sulfasalazine released approximately 70% of the 5-ASA load in simulated colonic fluid containing rat colon content in 24 h, whereas the chitosan-5-ASA azoconjugates released around 25% of the drug load over the same time period. Although the colon targeting potential of chitosan-5-ASA azoconjugates has been demonstrated, improving the drug delivery efficiency suggests a requirement for formulation of the chitosan-5-ASA azoconjugate as nanoparticles to increase the specific surface area and azo bond exposure to bacterial enzymes.