Department of Chemistry, East China University of Science and Technology, Shanghai, People's Republic of China.
Int J Nanomedicine. 2013;8:1879-86. doi: 10.2147/IJN.S42002. Epub 2013 May 10.
The objective of this study was to develop an oral microemulsion formulation of the antitumor diterpenoid agent, ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (henceforth referred to as 5F), to enhance its bioavailability and evaluate its hepatotoxicity. Pseudoternary phase diagrams showed that the optimal microemulsion formulation contained 45% water, 10% castor oil as the oil phase, 15% Cremophor EL as the surfactant, and 30% as a cosurfactant mixture of 1,2-propanediol and polyethylene glycol (PEG)-400 (2:1, w/w). The microemulsion preparation was characterized and its droplet diameter was within 50 nm. Release of 5F in vitro from the microemulsion was slightly increased compared with a suspension containing the same amount of active drug. Pharmacokinetic parameters in vivo indicated that bioavailability was markedly improved, with the relative bioavailability being 616.15% higher for the microemulsion than for the suspension. Toxicity tests showed that the microemulsion had no hepatotoxicity in mice. These results suggest the potential for 5F microemulsion to be administered by the oral route.
本研究旨在开发一种抗肿瘤二萜类药物，ent-11α-羟基-15-氧代-贝壳杉-16-烯-19-酸（以下简称 5F）的口服微乳制剂，以提高其生物利用度并评估其肝毒性。伪三元相图表明，最佳微乳制剂含有 45%的水、10%的蓖麻油作为油相、15%的聚氧乙烯失水山梨醇脂肪酸酯（吐温 80）作为表面活性剂和 30%的 1,2-丙二醇和聚乙二醇（PEG）-400（2:1，w/w）的混合助表面活性剂。对微乳制剂进行了表征，其粒径在 50nm 以内。与含有相同剂量活性药物的混悬剂相比，微乳制剂体外释放 5F 的速度略有增加。体内药代动力学参数表明，生物利用度显著提高，微乳制剂的相对生物利用度比混悬剂高 616.15%。毒性试验表明，微乳制剂在小鼠体内无肝毒性。这些结果表明，5F 微乳制剂具有经口服给药的潜力。
