Optimised Electroporation for Loading of Extracellular Vesicles with Doxorubicin

Autor: Angus J. Lennaárd, Doste R. Mamand, Rim Jawad Wiklander, Samir EL Andaloussi, Oscar P. B. Wiklander
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Pharmaceutics, Vol 14, Iss 1, p 38 (2021)
Druh dokumentu: article
ISSN: 14010038
1999-4923
DOI: 10.3390/pharmaceutics14010038
Popis: 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.
Databáze: Directory of Open Access Journals
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