No abstract

Exosomes are a kind of extracellular vesicle, has a particle size of 50–150 nm. Exosomes derived from different cell types are thought to participate in the regulation of cellular communication. On account of the ability of exosomes to deliver various cargos to a corresponding target site, they are often used to deliver therapeutic cargos for treatment. This review summarizes the origins and composition of exosomes, and provides a detailed overview of the current methods for exosome isolation and drug loading as well as the application of exosomes to drug delivery systems (DDSs) to provide practical suggestions for exosome studies. Moreover, this review also highlights the research progresses on plant-derived exosomes in determining their commonalities with and distinctions from animal-derived exosomes, and the advantages and challenges faced by plant-derived exosomes as drug delivery carriers are also discussed to contribute to the further application of plant-derived exosomes.

In vitro dissolution that predicts the in vivo performance of solid preparations is extremely important in formulation optimization. Fraction absorbed (F a ) has been used to screen in vitro dissolution protocols based on the idea of in vitro−in vivo correlation (IVIVC) but failed to increase the success rate due to the inaccuracy of the F a . The essence of IVIVC is the correlation between in vitro dissolution and in vivo dissolution. We tried to establish in vitro dissolution protocol via similarity with in vivo dissolution using aripiprazole (APZ) as a model drug. Hybrid APZ crystals (APZ-HCs) were prepared by physically embedding aggregation-caused quenching (ACQ) fluorophores inside the lattice to measure the in vivo dissolution. The process did not change the physicochemical properties and crystallinity of APZ. The fluorophore illuminated APZ crystals but was quenched upon dissolution of APZ-HCs in aqueous media, enabling monitoring intact APZ-HCs in real-time. The good correlation between fluorescent quenching and dissolution of APZ-HCs justified reliable quantification of intact APZ crystals. The residual percentage of fluorescence intensity in rats treated by APZ-HCs was recorded with time, which was converted to in vivo dissolution by the difference from 100%. The in vivo dissolution was validated with the F a . The in vitro dissolution profile of APZ was set up via a similarity factor larger than 50 in comparison with the in vivo dissolution. The study provides a novel idea and method to establish in vitro dissolution protocol.

The original article has been corrected to update corresponding author Rong Lu's second affiliation.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

As nano-drug carriers, small extracellular vesicles (sEVs) have shown unique advantages, but their drug loading and encapsulation efficiency are far from being satisfied, especially for the loading of hydrophilic small-molecule drugs. Inspired by the strategies of active loading of liposomal nanomedicines, pre-drug design and immobilization enzyme, here we developed a new platform, named “Esterase-responsive Active Loading” (EAL), for the efficient and stable drug encapsulation of sEVs. Widely used ferulic acid ester derivatives were chosen as prodrugs based on the EAL of engineered sEVs to establish a continuous transmembrane ion gradient for achieving efficient loading of active molecule ferulic acid into sEVs. The EAL showed that the drug loading and encapsulation efficiency were around 6-fold and 5-fold higher than passive loading, respectively. Moreover, characterization by nano-flow cytometry and Malvern particle size analyzer showed that differential ultracentrifugation combined with multiple types of membrane filtration methods can achieve large-scale and high-quality production of sEVs. Finally, extracellular and intracellular assessments further confirmed the superior performance of the EAL-prepared sEVs-loaded ferulic acid preparation in terms of slow release and low toxicity. Taken together, these findings will provide an instructive insight into the development of sEV-based delivery systems.