瘤内注射用醋酸奥曲肽温敏凝胶的处方筛选

Formula Selection of Octreotide Acetate Thermosensitive Hydrogels for Intratumor Injection

目的:筛选瘤内注射用醋酸奥曲肽温敏凝胶(OAG)的最佳处方。方法:以泊洛沙姆407、泊洛沙姆188为基质制备OAG,以胶凝温度(T)、黏度(η)及对小鼠腹水型肝癌高淋巴道转移细胞株HCA-F的抑制率(IR)为评价指标,考察泊洛沙姆的不同浓度、渗透压调节剂NaCl的加入及溶液pH等不同因素对OAG的影响,筛选主要处方组成并进行验证。结果:较佳处方组成为0.5%醋酸奥曲肽、18%泊洛沙姆407、12%泊洛沙姆188,0.9%NaCl,溶液pH调至7.2。验证试验中所制OAG的T为37.1℃,η为4750mPa.s,IR为57.6%,符合瘤内注射制剂的要求。结论:制备的OAG可满足瘤内注射给药和在体胶凝的要求,对肿瘤细胞的IR较高,具有较好的应用前景。

OBJECTIVE： To select the optimal formula of Octreotide acetate thermosensitive hydrogels （OAG） for intratumor injection. METHODS： OAG for intratumor injection was prepared using poloxamer 407 and poloxamer 188 as matrix. The effects of poloxamer concentration, addition of NaCl and pH value of solution on OAG were investigated. Optimum formula was selected by using the gelling temperature （T）, viscosity and inhibition rate （IR） on HCA-F cell line as index. RESULTS： Optimum formula was made up of 0.5% octreotide acetate, 18% poloxamer 407, 12% poloxamer 188, 0.9%NaCl and pH adjusted to 7.2. The gelling temperature of the thermosensitive hydrogels was 37.1℃, the viscosity was 4 750 mPa.s and the inhibition rate was 57.6% which was in accordance with the demands of intratumor injection. CONCLUSIONI Prepared OAG are up to the requirements of intratumor injection and in situ gelatinization and own high inhibition rate on tumor cell, so they have good prospect.