期刊
PHARMACEUTICS
卷 14, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14010038
关键词
extracellular vesicles; exosomes; doxorubicin; optimisation; electroporation; loading; chemotherapeutics; cytotoxins; intercellular transport; drug delivery platform; EV thawing temperature
资金
- Center for Medical Innovation (CIMED) [FoUI-963452]
- KI Research Foundation [2020-02022]
- H2020 EXPERT
- Swedish Foundation of Strategic Research (SSF-IRC) [IRC15-0065]
- ERC CoG (DELIVER)
- Swedish Research Council (VR-Med) [2020-01322]
- Swedish Research Council [2020-01322] Funding Source: Swedish Research Council
- Swedish Foundation for Strategic Research (SSF) [IRC15-0065] Funding Source: Swedish Foundation for Strategic Research (SSF)
Extracellular vesicles (EVs) have the potential to overcome limitations in clinical use of chemotherapeutics. By optimizing the electroporation technique, drugs can be efficiently loaded into EVs, leading to improved drug transport efficacy and therapeutic potency with reduced adverse effects.
The clinical use of chemotherapeutics is limited by several factors, including low cellular uptake, short circulation time, and severe adverse effects. Extracellular vesicles (EVs) have been suggested as a drug delivery platform with the potential to overcome these limitations. EVs are cell-derived, lipid bilayer nanoparticles, important for intercellular communication. They can transport bioactive cargo throughout the body, surmount biological barriers, and target a variety of tissues. Several small molecule drugs have been successfully incorporated into the lumen of EVs, permitting efficient transport to tumour tissue, increasing therapeutic potency, and reducing adverse effects. However, the cargo loading is often inadequate and refined methods are a prerequisite for successful utilisation of the platform. By systematically evaluating the effect of altered loading parameters for electroporation, such as total number of EVs, drug to EV ratio, buffers, pulse capacitance, and field strength, we were able to distinguish tendencies and correlations. This allowed us to design an optimised electroporation protocol for loading EVs with the chemotherapeutic drug doxorubicin. The loading technique demonstrated improved cargo loading and EV recovery, as well as drug potency, with a 190-fold increased response compared to naked doxorubicin.
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