Dendrimers conjugates for colonic delivery of 5-aminosalicylic acid.

The water-soluble polyamidoamine (PAMAM) dendrimer conjugates for colonic delivery of 5-aminosalicylic acid (5-ASA) were designed. The drug was bound to the dendrimer using two different spacers containing azo-bond, p-aminobenzoic acid (PABA) and p-aminohippuric acid (PAH). Incubation of PAMAM dendrimer conjugates containing PABA and PAH spacers with rat cecal contents at 37 degrees C gradually released 5-ASA with time and the amount of drug released was 45.6 and 57.0% of the dose in 24 h, respectively. The release of the drug from the commercial prodrug, sulfasalazine was significantly faster than both conjugates (80.2% of the dose in 6 h). No 5-ASA was detected from the incubation of dendrimer conjugates with the homogenate of the stomach or phosphate buffer, pH 1.2 and 6.8. Only a small amount of 5-ASA was found after incubation of both conjugates with the homogenate of the small intestine for 12 h. It appears that this PAMAM dendrimer can be developed for use as a carrier for colon-specific drug delivery.