透皮淋巴靶向长春新碱传递体

长春新碱(vincristine,VCR)临床主要用于治疗急性淋巴细胞白血病、何杰金及非何杰金淋巴瘤，疗效确切，但由于具有较大的神经系统毒性和局部刺激性，限制了其在临床上的应用。为增加VCR的淋巴靶向性，以增强疗效，降低其毒副作用，采用薄膜-超声分散法制备长春新碱传递体(VCR-T)，并考察其制剂学性质、药代动力学特征及靶向性。所制备的VCR-T平均粒径为63 nm，包封率为59%；改良Franz扩散池研究发现其体外透皮过程符合多项式方程，12 h累积透皮百分率为67.4%；HPLC法测定VCR在大鼠体内的药代动力学及组织分布，以VCR注射液为对照，VCR-T使VCR在血液中滞留时间延长了12倍，大鼠淋巴中靶向指数增加了2.75倍。传递体可良好地载带VCR透过皮肤进入体循环，具有较好的淋巴靶向性，可作为新型的淋巴靶向给药系统。

Transdermal and lymph targeting transfersomes of vincristine

Vincristine(VCR) is mainly used to treat acute lymphocytic leukemia,Hodgkin and non-Hodgkin lymphoma in clinic with definite therapeutic effect.But the obvious neurotoxicity and local stimulation of which limit its clinic use.In order to increase the lymph targeting to enhance the curative effect and to lower the adverse reaction of VCR,the VCR loaded transfersomes(VCR-T) were prepared with dry-film and ultrasonic dispersing methods,and the corresponding pharmaceutical properties,pharmacokinetical characteristics and the targeting ability were studied.The average particle size of VCR-T prepared was 63 nm with an entrapment ratio of 59%.The in vitro transdermal research with modified Franz cell showed that VCR-T permeated through the skin in accordance with polynomial equation,and with an accumulation permeation percentage of 67.4% up to 12 h.An HPLC method was utilized to determine the pharmacokinetics and tissue distribution of VCR.Compared with the iv injection of VCR solution,the retention time of VCR in blood was extended by 12 times with VCR-T,and the targeting index in rat lymph was increased by 2.75 times.As a result,transfersomes could penetrate the skin and enter into the systemic circulation carrying VCR with good lymph targeting ability,which makes it probably a new lymphtic targeting drug delivery system.