Synthesis and characterization of pH-sensitive dextran hydrogels as a potential colon-specific drug delivery system

Abstract

pH-Sensitive dextran hydrogels were prepared by activation of dextran (T-70) with 4-nitrophenyl chloroformate, followed by conjugation of the activated dextran with 4-aminobutyric acid and cross-linking with 1,10-diaminodecane. The cross-linking efficiencies determined by mechanical measurements were in the range of 52-63%. Incorporation of carboxylpropyl groups in dextran hydrogels led to a higher equilibrium and faster swelling under high pH conditions. The swelling reversibility of hydrogels was also observed after repeated changes in buffers between pH 2.0 and 7.4. The slow rates of swelling and deswelling in response to changes in pH were attributed to the hydrophilic nature of dextran and formation of hydrogen bonds between the hydroxyl groups of dextran with water molecules. The pronounced effect of carboxylic acid content on degradation of hydrogels was observed after 4 h of incubation with dextranase and the influence significantly decreased after exposure to the enzyme for 8 h. The mechanism of bulk degradation of hydrogels under high swelling extent was substantiated using Coomassie blue protein assay. The release rate of bovine serum albumin from hydrogels was primarily determined by the swelling extent. The release rate was further enhanced by addition of dextranase in buffer solutions.

Synthesis and characterization of acrylic type hydrogels containing azo derivatives of 5-amino salicylic acid for colon-specific drug delivery

“…Colon targeting is naturally of value for the topical treatment of diseases of colon such as Crohn's diseases, ulcerative colitis, colorectal cancer and amebiasis. The various strategies for targeting orally administered drugs to the colon include covalent linkage of a drug with a carrier, coating with pH-sensitive polymers, formulation of time released systems, exploitation of carriers that are degraded specifically by colonic bacteria, bioadhesive systems and osmotic controlled drug delivery systems (Bajpai and Saxena, 2004;Chiu et al,1999;Mahkam, 2004;Rubinstein, 2000). One strategy for targeting orally administered drugs to the colon includes covalent linkage between drug and pH-sensitive hydrogel in such a manner that upon oral administration the moiety remains intact in the stomach and small intestine.…”

Stimuli-responsive hydrogels in drug delivery and tissue engineering

“…(g) Monomers and crosslinkers used in the synthesis of the hydrogels are not biocompatible, i.e. they may be toxic, carcinogenic or teratogenic (Chiu et al, 1999). (h) One of the major limitation of pH-sensitive polymers is their non-biodegradability.…”

Polysaccharide Based Formulations for Mucosal Drug Delivery: A Review

“…1997 [190] Guar gum Indomethacin Matrix tablet 1998 [191] Guar gum Technetium-99m-DTPA Matrix tablet 1998 [192] Guar gum 5-ASA Compression coat 1999 [193] Cross-linked guar --1995a [194] Cross-linked guar Hydrocortisone Hydrogels 2000 [195] Crosslinked dextranHydrogels 1995a [196] pH-sensitive dextran Bovine serum albumin (BSA) Hydrogels 1999 [197] Cross-linked dextran Hydrocortisone Capsules 1998 [198] Dextran fatty acid esters Locust bean gum Theophylline Film 1995 [208] In a related study, Feng and co-workers used chitosan based nanogels obtained by electrostatic interaction between chitosan and carboxy-methyl chitosan for delivering drugs against colorectal cancer and showed significant effect on cell viability owing to the improved mucoadhesion which allowed a higher accumulation of drug (doxorubicin) concentration within the cancer site [210].…”