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.
Wiwattanapatapee
Ruedeekorn
R
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkla 90112, Thailand.
Lomlim
Luelak
L
Saramunee
Krisanee
K
D010129:4-Aminobenzoic Acid / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003106:Colon; D003692:Delayed-Action Preparations; D050091:Dendrimers; D016503:Drug Delivery Systems; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000737:chemistry; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D010130:p-Aminohippuric Acid / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D050091:Dendrimers; C104700:PAMAM Starburst; D011073:Polyamines; D019804:Mesalamine; D010129:4-Aminobenzoic Acid; D010130:p-Aminohippuric Acid