Abstract 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 in vitro 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.

中文翻译：

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聚乙二醇化三甲基壳聚糖乳剂与奥曲肽偶联，用于将索拉非尼靶向递送至 HepG2 肝细胞癌细胞

摘要 本研究旨在开发与奥曲肽偶联的聚乙二醇化三甲基壳聚糖 (TMC) 包被的乳化体 (EM)，用于将索拉非尼靶向递送至 HepG2 的肝细胞癌细胞 (HCC)。负载索拉非尼 TMC 包被的 EMs 是通过乳液蒸发法制备的，并表征了粒径、zeta 电位、药物包封效率和体外药物释放。然后将合成的 EM 与奥曲肽结合。通过对 HepG2 细胞的细胞摄取和 MTT 测定确定靶向和非靶向 EM 的细胞毒性。还使用流式细胞术研究了细胞周期测定。结果表明，优化后的EMs粒径为127 nm，zeta电位为-5.41 mV，加载效率为95%，52 h内药物释放效率为62%。奥曲肽有效地附着在 EMs 的表面上，高达 71%。MTT 测定和细胞摄取研究表明，靶向 EM 比游离索拉非尼和非靶向 EM 具有更高的细胞毒性。细胞周期分析显示，与游离索拉非尼和非靶向 EMs 相比，G1 期靶向 EMs 处理的 HepG2 细胞的积累显着更多。结果表明，设计的 EM 可能有希望用于治疗肝细胞癌。