PEGylated trimethylchitosan emulsomes conjugated to octreotide for targeted delivery of sorafenib to hepatocellular carcinoma cells of HepG2

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.

Keywords:

• Sorafenib
• octreotide
• drug targeting
• emulsomes
• hepatocellular carcinoma

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by a grant [No. 397319] from Isfahan University of Medical Sciences, Iran.