Erythrocyte membrane vesicles as drug delivery systems: A systematic review of preclinical studies on biodistribution and pharmacokinetics

This systematic review aims to summarize the development of erythrocyte membrane vesicles (EMVs) as drug delivery carriers, with a focus on elucidating their fate in terms of biodistribution and pharmacokinetics in preclinical studies. The PubMed database was systematically reviewed to search for original peer-reviewed published studies on the use of EMVs for drug delivery to summarize the preclinical findings, following the PRISMA guidelines. A total of 142 articles matched the selection criteria and were included in the review. For each study, the following parameters were extracted: type of active pharmaceutical ingredient (API) encapsulated into EMVs, EMVs-API formulation method and final particle size, EMVs surface modifications for active targeting, cell lines and animal models used in the study, crucial treatment data, biodistribution data and finally, where applicable, data about the EMVs circulation time and blood half-life. EMVs size did not vary significantly among the different formulation methods. A complete list of cell lines and animal models used is provided. Circulation times and data for blood half-life were grouped per animal type. For the most commonly used animal type, BALB/c mice, the average half-life of EMV-API was calculated to be 10.4 h, and in all cases, up to a 10-fold increase was observed compared with that of free API. Surface modifications did not drastically change the circulation time but did improve target tissue accumulation. The most critical weaknesses in the analysed studies were identified. Key points for future studies are provided to fill the current knowledge gaps and improve the quality of publications.