Development and application of novel w/o/w emulsion for the chemoembolization therapy of hepatocellular carcinoma

采用两步乳化法制备了水溶性抗癌剂盐酸表阿霉素W/O/W乳剂(WOWE)。所使用的水相和油相分别为非离子(碘海醇)和油性(碘化油)收缩介质。内、外水相中分别加入聚氧乙烯水合蓖麻油60和明胶，WOWE是稳定的乳状液，能包埋大量EPI，粘度小。溶血率低于常规介入化疗栓塞术(TAE)所用O/W乳剂(OWE)。将含和不含EPI的乳剂分别注入大鼠尾静脉。OWE(1.5ml/kg)组大鼠在2天内死于肺水肿。WOWE(2.0ml/kg)灌胃给药后7~9天，大鼠因EPI的毒性而死亡，死亡大鼠出现胃部充血、溃疡和胸腺缩小。结果表明，将EPI包裹在WOWE液滴中，可降低EPI的急性毒性。因此，我们新制备的WOWE比OWE更安全，也是治疗TAE的理想制剂。目前，WOWE的有效性正在研究中，WOWE的临床应用也在研究中。

W/o/w emulsion (WOWE) encapsulating water-soluble anticancer agent (epirubicin hydrochloride, EPI) was prepared by two-step amulsification method. Aqueous and oil phases used were nonionic (iohexol) and oily (lipiodol) contract media, respectively. The agents added in inner and outer aqueous phases were polyoxyethylene hydrated caster oil 60 and gelatin, respectively.The WOWE was stable emulsion which could encapsulate large amount of EPI and the viscosity was small. The hemolysis percentage was less than that of the o/w emulsion (OWE) used for transcatheter chemoembolization therapy (TAE) conventionally.The acute toxicities of WOWE and OWE were investigated. The emulsions with and without EPI were administered to the tail vein of rats. The rats administered OWE (*1.5 ml/kg) were deceased within 2 days by pulmonary edema. The rats administered WOWE (*2.0 ml/kg) encapsulating EPI were deceased 7-9 days after administration by the toxicity of EPI.Bleeding and ulcer in the stomach and size reduction of thymus gland were observed in these deceased rats. These pathological damage in the stomach and thymus gland were observed in the rats administered less amounts of OWE than WOWE.This result suggests that the encapsulation of EPI in the WOWE droplets reduced the acute toxicity of EPI.Therefore, the WOWE newly prepared by us was safer than OWE and desirable formulation for TAE.The effectiveness of WOWE is investigated now and the possible clinical application of WOWE is under investigation.