Oral delivery of gemcitabine loaded CSKSSDYQC peptide conjugated N-trimethyl chitosan nanoparticles to treat cancer: Synthesis, characterization and animal studies

European Chemistry Congress

June 16-18, 2016 Rome, Italy

Guanyu Chen, Darren Svirskis, Weiyue Lu, Man Ying, Yuan Huang and Jingyuan Wen

University of Auckland, New Zealand
Fudan University, China
Sichuan University, China

Posters & Accepted Abstracts: Chem Sci J

Abstract :

The oral delivery of anticancer drugs represents a significant challenge for global scientist. N-trimethyl chitosan (TMC) is a polymer with the potential to facilitate effective oral drug delivery. Recently, the peptide CSKSSDYQC (CSK) has been conjugated to TMC as a means of active goblet cell targeting for gastrointestinal uptake. The aim of the study is to develop and optimize a TMC-CSK modified nanoparticules for oral delivery of gemcitabine. TMC was synthesised from deacetylated chitosan using a novel two-step synthesis, then conjugated with CSK to actively target goblet cells. Gemcitabine-loaded TMCCSK nanoparticles were prepared via ionic gelation. Characterisation studies including particle size, zeta potential, entrapment efficiency and in vitro drug release were then carried out. Cytotoxicity of drug solution and drug loaded formulation was tested on 4T1 breast cancer cell. Lastly, in-vivo pharmacokinetic and pharmacodynamics studies were conducted. The results showed the optimal delivery system showed particle size of 173.6�±7.7 nm and zeta potential of 18.5�±0.2 mV. Entrapment efficiency of 66.44�±0.02%, and a sustained drug release profile was obtained. LD50 of 0.23 �µg/mL was determined in cytotoxicity studies. Gemcitabine loaded TMC-CSK nanoparticles significantly improved the oral bioavailability, raised the plasma half-life, and AUC0-â�� of 4.5 fold higher than for gemcitabine solution in pharmacokinetic studies. Obvious tumour size reduction of 2.6 fold was observed for TMC-CSK nanoparticles compared to drug solution in pharmacodynamics studies. In conclusion, gemcitabine can be delivered using this TMC-CSK modified nanoparticulate delivery systems via oral route to elevate its oral bioavailability and therapeutic anticancer effect. gs.chen@auckland.ac.nz