title: Intravenous microemulsion of docetaxel containing an anti-tumor synergistic ingredient (Brucea javanica oil): formulation and pharmacokinetics.
abstract: The purpose of this study was to develop a docetaxel microemulsion containing an anti-tumor synergistic ingredient (Brucea javanica oil) and to investigate the characteristics of the microemulsion. Brucea javanica oil contains oleic acid and linoleic acids that have been shown by animal and human studies to inhibit tumor formation. The microemulsion containing Brucea javanica oil, medium-chain triglyceride, soybean lecithin, Solutol®HS 15, PEG 400, and water was developed for docetaxel intravenous administration. A formulation with higher drug content, lower viscosity, and smaller particle size was developed. The droplet size distribution of the dispersed phase of the optimized microemulsion was 13.5 nm, determined using a dynamic light scattering technique. The small droplet size enabled the microemulsion droplets to escape from uptake and phagocytosis by the reticuloendothelial system and increased the circulation time of the drug. The zeta potential was -41.3 mV. The optimized microemulsion was pale yellow, transparent, and non-opalescent in appearance. The value of the combination index was 0.58, showing that there was a synergistic effect when docetaxel was combined with Brucea javanica oil. After a single intravenous infusion dose (10 mg/kg) in male Sprague Dawley rats, the area under the curve of the microemulsion was higher and the half-time was longer compared with that of docetaxel solution alone, and showed superior pharmacokinetic characteristics. These results indicate that this preparation of docetaxel in emulsion is likely to provide an excellent prospect for clinical tumor treatment.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors.forename: Shilin
authors.initials: S
authors.lastname: Ma
authors.forename: Fen
authors.initials: F
authors.lastname: Chen
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ye
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Dong
authors.forename: Yingna
authors.initials: Y
authors.lastname: Xue
authors.forename: Heming
authors.initials: H
authors.lastname: Xu
authors.forename: Wenji
authors.initials: W
authors.lastname: Zhang
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Song
authors.forename: Li
authors.initials: L
authors.lastname: Ai
authors.forename: Naixian
authors.initials: N
authors.lastname: Zhang
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D032269:Brucea / Q000737:chemistry*; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077143:Docetaxel; D004339:Drug Compounding / Q000379:methods; D004357:Drug Synergism; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010316:Particle Size; D010938:Plant Oils / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D004655:Emulsions; D010938:Plant Oils; D043823:Taxoids; D000077143:Docetaxel
keywords: docetaxel; formulation; microemulsion; pharmacokinetic; synergistic ingredient