Extracellular vesicles (EVs) are naturally secreted, non-nuclear lipid nanostructures by organic sources with intrinsic options similar to biocompatibility, low immunogenicity, and the power to bypass organic obstacles. Regardless of the rising curiosity in EV analysis, their organic potential as a flexible drug supply automobile has but to be extensively translated for scientific use. Fewer than 3 % of scientific trials involving these cell-free vesicles have utilized them for drug supply functions. This evaluate elucidates the explanations behind the translational hole by a complete evaluation of pharmacokinetic and tissue transport challenges confronted by EVs throughout numerous tissue obstacles, together with the cartilage, blood-brain interface, ocular, gastrointestinal, and pores and skin tissues, and summarizes their endogenous roles inside these tissue microenvironments. The evaluate additionally delves into key engineering design ideas, presenting a portfolio of each tissue-specific and tissue-independent concentrating on methods to beat tissue obstacles and improve the exact supply of engineered EVs. A complete comparability of key components – similar to biodistribution, mobile uptake, intracellular destiny, and security profile – between EVs and benchmark artificial platforms can also be offered to information the number of optimum provider designs for various tissue targets and additional highlights the steps wanted to bridge translational gaps of engineered EVs from a scientific perspective. In conclusion, the evaluate underscores the importance of engineered EVs as a promising next-generation nanocarrier for precision nanomedicine, providing an alternative choice to typical artificial platforms.

