包载紫杉醇的透明质酸功能化乳剂对卵巢癌治疗效果研究  

Enhanced efficacy of paclitaxel-loaded hyaluronic acid functional emulsion in the treatment of ovarian cancer

作　　者：孙晓峰 阳松威 杨硕[3] 罗令[4] SUN Xiao-feng;YANG Song-wei;YANG Shuo;LUO Ling(Department of Embryology,Hunan University of Traditional Chinese Medicine,Changsha 410006,China;Department of Pharmacy,Hunan University of Traditional Chinese Medicine,Changsha 410006,China;College of Integration of Traditional Chinese and Western Medicine,Hunan University of Traditional Chinese Medicine,Changsha 410006,China;Department of Orthopedics,Third Xiangya Hospital,Central South University,Changsha 410013,China)

机构地区：[1]湖南中医药大学医学院组胚教研室,长沙410006 [2]湖南中医药大学药学院,长沙410006 [3]湖南中医药大学中西结合学院,长沙410006 [4]中南大学湘雅三医院骨科,长沙410013

出　　处：《中国新药杂志》2018年第18期2180-2187,共8页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81774362;81303004)

摘　　要：目的:制备紫杉醇(paclitaxel,PTX)的透明质酸固体纳米乳剂(PTX-HSNs)用于递送PTX,以改善卵巢癌治疗效果。方法:采用高压均质设备制造PTX-HSNs,对PTX-HSNs进行材料表征,并在体内外评估其性能。结果:PTX-HSNs平均粒径<100 nm,PTX包载量3 mg·mL^(-1),包封率(EE)接近100%。通过PTXHSN和不含乙酰透明质酸的PTX固体纳米乳剂(PTX-SNs)对SK-OV-3(分化簇44[CD_(44)^+])细胞和OVCAR-3(CD_(44)^-)细胞的作用比较,表明PTX-HSN与SK-OV-3细胞的亲和能力比PTX-SNs高上百倍。PTX-HSNs的最大耐受剂量(MTD)>50 mg PTX·kg^(-1),比Taxol高2.5倍。小鼠肿瘤移植中显示,PTX-HSN治疗比Taxol治疗毒性小,PTX-HSN有效抑制体内肿瘤生长。PTX-HSN治疗后,PTX的循环时间延长,PTX在卵巢肿瘤组织中的滞留增加。结论:PTX-HSN是具有高MTD的高效纳米系统,用于递送PTX至卵巢癌,并具有对CD44过表达肿瘤靶向和低毒性的特征。Objective： To fabricate paclitaxel-loaded hyaluronan solid nanoemulsions（ PTX-HSNs） for the delivery of PTX to improve ovarian cancer treatment via active tumor targeting. Methods： PTX-HSNs were fabricated using high-pressure homogenization and were lyophilized with d-mannitol. The outside of the PTX-HSNs spheres were coated with hyaluronan. Results： The mean size of the PTX-HSNs was maintained to be less than 100 nm,with a relatively narrow size distribution. The PTX loading content was 3 mg·mL^-1,and encapsulation efficiency（ EE） was close to 100%. The effects of PTX-HSNs and hyaluronan-free PTX-loaded solid nanoemulsions（ PTXSNs） on SK-OV-3（ cluster of differentiation 44 [CD44＋]） cells and OVCAR-3（ CD44-） cells were compared,and it was shown that PTX-HSNs had hundreds of times higher affinity for SK-OV-3 cells than PTX-SNs. The maximum tolerated dose（ MTD） of PTX-HSNs was greater than 50 mg PTX·kg^-1,which was 2. 5-fold higher than that of Taxol when administered by injection. Less toxicities were observed in tumor-transplanted mice compared to Taxol.The pharmacokinetic parameters of PTX-HSNs were more desirable than those of Taxol. PTX-HSNs treatment effectively inhibited tumor growth in vivo. After PTX-HSNs administration,the circulation time of PTX wasprolonged and the retention of PTX in ovarian tumor tissues was increased. Conclusion： PTX-HSNs is a highly effective nanosystem with a high MTD for delivering PTX to ovarian cancers characterized by CD44 overexpression,enhanced active tumor targeting,and low toxicity.

关 键 词：紫杉醇 透明质酸固体纳米乳 靶向 最大耐受剂量 疗效 

分 类 号：R285.5[医药卫生—中药学] R944[医药卫生—中医学]