Poly(sebacic acid-co-ricinoleic acid) biodegradable carrier for paclitaxel: in vitro release and in vivo toxicity.
Polyesteranhydrides synthesized by the transesterification of ricinoleic acid and sebacic acid followed by anhydride polymerization were examined as potential controlled delivery carrier for paclitaxel. Solid and liquid polymers were used. Polymers containing 30% ricinoleic acid are solid whereas polymers containing 70% ricinoleic acid are liquid at body temperature and semisolid at room temperature. It was found that upon addition of the liquid polymer to water it solidifies to form a stable semisolid. Paclitaxel, a potent antitumor agent, was incorporated in the polymers (5-20% w/w) and its release in buffer solution was monitored. Paclitaxel was released for over 100 days while the polymer carrier was being degraded. The release rate was affected by the paclitaxel content; the higher the content, the slower was the release. The toxicity of the polymers and formulations with paclitaxel was examined by subcutaneous injection of liquid polymer samples or implantation of solid polymer specimens to mice for different time periods. Histopathological examination of the tissue surrounding the implant showed minor inflammation 1 week after the injection and no inflammation 3 weeks after implantation. Injection of the polymer without paclitaxel showed no adverse effects.
Department of Medicinal Chemistry and Natural Products, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
Ariella
A
Shikanov
Boris
B
Vaisman
Michal Y
MY
Krasko
Abraham
A
Nyska
Abraham J
AJ
Domb
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000633:toxicity; D001673:Biodegradation, Environmental; D003652:Decanoic Acids / Q000633:toxicity*; D003692:Delayed-Action Preparations / Q000633:toxicity; D003877:Dermatitis, Contact / Q000209:etiology / Q000473:pathology; D003998:Dicarboxylic Acids / Q000633:toxicity*; D004337:Drug Carriers / Q000633:toxicity; D004343:Drug Implants; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000008:administration & dosage* / Q000633:toxicity; D011108:Polymers / Q000633:toxicity*; D012277:Ricinoleic Acids / Q000633:toxicity*
D000972:Antineoplastic Agents, Phytogenic; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids; D004337:Drug Carriers; D004343:Drug Implants; C493322:Poly(sebacic acid-co-ricinoleic acid); D011108:Polymers; D012277:Ricinoleic Acids; C011107:sebacic acid; C030521:ricinoleic acid; D017239:Paclitaxel