title: Poly(sebacic acid-co-ricinoleic acid) biodegradable carrier for paclitaxel--effect of additives.
abstract: Injectable polymeric formulation for paclitaxel was studied. Poly ricinoleic acid and sebacic acid were synthesized. The effect of additives on the viscosity of polymer, paclitaxel release, and polymer degradation was investigated both in vitro and in vivo. Additives that were used in this study were ricinoleic acid, phospholipid, PEG 400, and PEG 2000. Addition of 20% ricinoleic acid to P(SA:RA)3:7 liquefied the formulation and allowed injection of the formulation containing paclitaxel via a 22-G needle at room temperature with no effect on paclitaxel release rate. Addition of PEG 400, PEG 2000, and phospholipid to the formulation did not affect the paclitaxel release from the formulation. The degradation of modified formulations with paclitaxel and additives was examined in vitro and by subcutaneous injection of liquid formulations to the backspace via a 22-G needle into seven groups of four C3H mice. In vivo formulations with additives (20% ricinoleic acid and PEG or phospholipid) and 5% paclitaxel content degraded faster than the formulation with only 20% ricinoleic acid and the same paclitaxel content: 51% and 54% versus 43%. The slowest degradation (26% in 1 week) was of the formulation containing 10% paclitaxel. The release rate in vivo was affected by the paclitaxel content; the higher the content, the slower was the release. By using additives, we could adjust the physical characteristics of the surgical paste while maintaining a desirable system for sustained paclitaxel release.
authors.affiliation: Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Shikanov
authors.forename: Aviva
authors.initials: A
authors.lastname: Ezra
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003652:Decanoic Acids / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006868:Hydrolysis; D051379:Mice; D008809:Mice, Inbred C3H; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D014677:Pharmaceutical Vehicles; D010743:Phospholipids; D011092:Polyethylene Glycols; D011108:Polymers / Q000737:chemistry*; D012277:Ricinoleic Acids / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014783:Viscosity
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003652:Decanoic Acids; D004337:Drug Carriers; D014677:Pharmaceutical Vehicles; D010743:Phospholipids; C493322:Poly(sebacic acid-co-ricinoleic acid); D011108:Polymers; D012277:Ricinoleic Acids; D011092:Polyethylene Glycols; D017239:Paclitaxel