Shikanov Ariella, Ezra Aviva, Domb Abraham J
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
J Control Release. 2005 Jun 20;105(1-2):52-67. doi: 10.1016/j.jconrel.2005.02.018.
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.
对用于紫杉醇的可注射聚合物制剂进行了研究。合成了聚蓖麻油酸和癸二酸。在体外和体内研究了添加剂对聚合物粘度、紫杉醇释放和聚合物降解的影响。本研究中使用的添加剂有蓖麻油酸、磷脂、聚乙二醇400（PEG 400）和聚乙二醇2000（PEG 2000）。向聚（癸二酸：蓖麻油酸）3:7中添加20%的蓖麻油酸可使制剂液化，并允许在室温下通过22号针头注射含紫杉醇的制剂，且对紫杉醇释放速率无影响。向制剂中添加PEG 400、PEG 2000和磷脂不会影响制剂中紫杉醇的释放。通过22号针头将含紫杉醇和添加剂的改良制剂皮下注射到七组每组四只C3H小鼠的背部间隙，在体外和体内研究了其降解情况。含添加剂（20%蓖麻油酸和PEG或磷脂）且紫杉醇含量为5%的体内制剂比仅含20%蓖麻油酸且紫杉醇含量相同的制剂降解更快：分别为51%和54%，而后者为43%。含10%紫杉醇的制剂降解最慢（1周内为26%）。体内释放速率受紫杉醇含量影响；含量越高，释放越慢。通过使用添加剂，我们可以在维持理想的紫杉醇持续释放系统的同时调整手术糊剂的物理特性。
