Development of a polymeric surgical paste formulation for taxol

• Published in: Pharmaceutical research 1996-03, Vol.13 (3), p.368-375
• Main Authors: WINTERNITZ, C. I, JACKSON, J. K, OKTABA, A. M, BURT, H. M
• Format: Article
• Language: English
• Subjects: Allantois - blood supply; Allantois - drug effects; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Biological and medical sciences; Chemistry, Pharmaceutical; Chick Embryo; Chorion - blood supply; Chorion - drug effects; General pharmacology; Medical sciences; Neovascularization, Physiologic - drug effects; Ointments; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Paclitaxel - pharmacology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyesters - chemistry; Polyethylene Glycols - chemistry
• ISSN: 0724-8741
• DOI: 10.1023/A:1016032207246

To develop and characterize a biodegradable polymeric sustained release surgical paste formulation for taxol. Taxol was incorporated into poly(epsilon-caprolactone) (PCL) or blends of PCL with methoxypolyethylene glycol, MW 350 (MePEG). The surgical pastes were characterized using gel permeation chromatography, thermal analysis, scanning electron microscopy, and a tensile strength tester. In vitro release data for taxol from the surgical paste formulations was carried out at 37 degrees C in phosphate buffered saline, pH 7.4, using an HPLC assay for taxol. Antiangiogenic activity of the formulations were assessed using a chick chorioallantoic membrane assay (CAM). The addition of up to 30% MePEG in PCL decreased the melting point of PCL by 5 degrees C and the tensile strength by 152.7 N/cm2 to 26.7 N/cm2 but increased the degree of PCL crystallinity from 42% to 51%. Taxol showed a biphasic in vitro release profile composed of a burst phase lasting 1 or 2 days followed by a period of slow sustained drug release. There was no significant difference in the release profiles of taxol from two different sources of PCL. The addition of MePEG increased the amount of water taken up by the polymer blends but decreased the rate of taxol release. The formulations were shown to have antiangiogenic activity by the CAM assay at levels as low as 0.1% taxol using 3 mg surgical paste pellets. Our surgical paste formulations for taxol give sustained release while having physical properties which can be adjusted using additives.