Ricinoleic acid-based biopolymers.
Polyanhydrides synthesized from pure ricinoleic acid half-esters with maleic and succinic anhydrides possess desired physicochemical and mechanical properties for use as drug carriers. Ricinoleic acid maleate or succinate diacid half-esters were prepared from the reaction of crude ricinoleic acid (85% content) with succinic or maleic anhydride. The pure diacid monomers were obtained by chromatography purification through silica gel using petroleum ether/ethyl acetate/acetic acid (80/30/1 v/v/v) mixture as eluent. The pure diacid monomers (>99%) were polymerized by melt condensation to yield film-forming polymers with molecular weights exceeding 40,000 with a polydispersity of 2. Extensive biocompatibility study demonstrated their toxicological inertness and biodegradability. Their rate of elimination from rats in the course of about 4-6 weeks was faster than that found for similar fatty acid-based polyanhydrides previously tested. In vitro studies showed that these polymers underwent rapid hydrolytic degradation in 10 days. Methotrexate release from the polymers was not affected by the initial polymer molecular weight in the range of 10,000-35,000. The in vitro drug release correlated with the degradation of the polymers. The fatty acid ester monomers were further degraded to its counterparts, ricinoleic acid and succinic or maleic acid.
Department of Medicinal Chemistry, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
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D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry; D003652:Decanoic Acids / Q000138:chemical synthesis / Q000737:chemistry; D003998:Dicarboxylic Acids; D004058:Diffusion; D004337:Drug Carriers; D005260:Female; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D008727:Methotrexate / Q000008:administration & dosage / Q000737:chemistry; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D012277:Ricinoleic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013228:Stearates / Q000737:chemistry; D013386:Succinates / Q000737:chemistry; D015430:Weight Gain / Q000187:drug effects
C407565:12-hydroxystearic acid succinate; D001672:Biocompatible Materials; D002264:Carboxylic Acids; D003652:Decanoic Acids; D003998:Dicarboxylic Acids; D004337:Drug Carriers; D012277:Ricinoleic Acids; D013228:Stearates; D013386:Succinates; C011107:sebacic acid; D008727:Methotrexate