Enhanced cellular uptake and intracellular drug controlled release of VESylated gemcitabine prodrug nanocapsules

Colloids and Surfaces. B, Biointerfaces
Yanfen FangJiahui Yu

Abstract

Gemcitabine, 2',2'-difluoro-2'-deoxycytidine (dFdC), is the first-line antitumor agent in the treatment of pancreatic tumors. However, it possesses certain drawbacks, such as poor biological half-life resulted from rapid metabolism and the induction of resistance, leading to its restricted therapeutic potential. With the purpose of overcoming the above drawbacks, we developed a novel VESylated gemcitabine (VES-dFdC) prodrug by coupling the N4-amino group of the pyrimidine ring of dFdC to the carboxylic group of vitamin E succinate (VES). The resulting amphiphilic compound could protect the N4-amino group of the pyrimidine ring of dFdC from being degraded by cytidine deaminase. What is more, the prodrug was able to form nanocapsules in aqueous media (similar to the structure of cytomembrane), confirmed by transmission electron microscope (TEM). Their average particle size is about 107 nm with zeta potential of -33.4 mV measured by dynamic light scattering (DLS). VES-dFdC nanocapsules showed accelerated accumulative drug release profile in simulated lysosome environment (sodium acetate buffer pH 5+cathepsin B, an enzyme in lysosome), due to the easily hydrolyzed property of amide bond by cathepsin B, while rather stable in PBS (p...Continue Reading

References

Aug 10, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·L BildsteinP Couvreur
Aug 20, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Woon-Gye ChungZhengrong Cui

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Citations

Mar 24, 2018·ChemMedChem·Katherine J SkillingMaria Marlow
Nov 17, 2017·Cancers·Manoj Amrutkar, Ivar P Gladhaug
Mar 9, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Ai-Mei LiaoChangJu Chun
Apr 6, 2021·Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes·Ya WangXiaogang Li

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