Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences , Isfahan , Iran.
Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences , Isfahan , Iran.
J Liposome Res. 2019 Dec;29(4):383-398. doi: 10.1080/08982104.2019.1570250. Epub 2019 Mar 14.
The current study aimed to develop PEGylated trimethyl chitosan (TMC) coated emulsomes (EMs) conjugated with octreotide for targeted delivery of sorafenib to hepatocellular carcinoma cells (HCC) of HepG2. Sorafenib loaded TMC coated EMs were prepared by the emulsion evaporation method and characterized concerning particle size, zeta potential, drug encapsulation efficiency, and drug release. Synthesized EMs were then conjugated to octreotide. The cytotoxicity of the targeted and non-targeted EMs was determined by cellular uptake and MTT assay on HepG2 cell. Cell cycle assay was also studied using flow cytometry. The results showed the optimized EMs had the particle size of 127 nm, zeta potential of -5.41 mV, loading efficiency of 95%, and drug release efficiency of 62% within 52 h. Octreotide was attached efficiently to the surface of EMs as much as 71%. MTT assay and cellular uptake studies showed that targeted EMs had more cytotoxicity than free sorafenib and non-targeted EMs. Cell cycle analyses revealed that there was a significant more accumulation of targeted EMs treated HepG2 cells in the G1 phase than free sorafenib and non-targeted EMs. The results indicate that designed EMs may be promising for the treatment of hepatocellular carcinoma.
本研究旨在开发聚乙二醇化三甲基壳聚糖（TMC）包被的乳剂（EMs），并将其与奥曲肽偶联，以实现索拉非尼靶向递送至 HepG2 肝癌细胞（HCC）。通过乳化蒸发法制备载有索拉非尼的 TMC 包被的 EMs，并对其粒径、Zeta 电位、药物包封效率和药物释放进行了表征。然后将合成的 EMs 与奥曲肽偶联。通过细胞摄取和 HepG2 细胞的 MTT 测定来确定靶向和非靶向 EMs 的细胞毒性。还通过流式细胞术研究了细胞周期测定。结果表明，优化后的 EMs 的粒径为 127nm，Zeta 电位为-5.41mV，载药效率为 95%，在 52h 内药物释放效率为 62%。奥曲肽有效地附着在 EMs 表面，附着率高达 71%。MTT 测定和细胞摄取研究表明，靶向 EMs 比游离索拉非尼和非靶向 EMs 具有更高的细胞毒性。细胞周期分析表明，与游离索拉非尼和非靶向 EMs 相比，用靶向 EMs 处理的 HepG2 细胞在 G1 期的积累明显更多。结果表明，设计的 EMs 可能是治疗肝癌的有前途的方法。
