Plant derived extracellular vesicles (EVs) are nano-sized membranous vesicles released by plant cells, which contain lipids, proteins, nucleic acids and specific pharmacologically active substances. They are safe, widely available and expediently extractive. They have gratifyingly biological activity against inflammation, cancer, bacteria and oxidative aging, especially for the prevention or treatment of colitis, cancer, alcoholic liver, and COVID-19. In addition, as natural drug carriers, plant derived EVs have the potential to target the delivery of small molecule drugs and nucleic acid through oral, transdermal, injection. With the above advantages, plant derived EVs are expected to have excellent strong competitiveness in clinical application or preventive health care products in the future. We comprehensively reviewed the latest separation methods and physical characterization techniques of plant derived EVs, summarized the application of them in disease prevention or treatment and as a new drug carrier, and analyzed the clinical application prospect of plant derived EVs as a new drug carrier in the future. Finally, the problems hindering the development of plant derived EVs at present and consideration of the standardized application of them are discussed.
The mechanisms and applications of chitosan and its derivatives in transdermal drug delivery to promote drug permeation were reviewed in this paper. Specifically, we summarized the permeation-promoting mechanisms of chitosan and several of its derivatives, including changing the structure of stratum corneum proteins, acting on the tight junction of granular layers, affecting intercellular lipids, and increasing the water content of stratum corneum. These mechanisms are the reason why chitosan and its derivatives can increase the transdermal permeation of drugs. In addition, various transdermal preparations containing chitosan and its derivatives were summarized, and their respective advantages were expounded, including nanoparticles, emulsions, transdermal microneedles, nanocapsules, transdermal patches, transdermal membranes, hydrogels, liposomes, and nano-stents. The purpose of this review is to provide a theoretical basis for the further and wider application of chitosan in transdermal drug delivery systems. In the future, research results of chitosan and its derivatives in transdermal drug delivery need more support from in vivo experiments, as well as good correlation between in vitro and in vivo experiments. In conclusion, the excellent permeability-promoting property, good biocompatibility, and biodegradability of chitosan and its derivatives make them ideal materials for local transdermal drug delivery.
Efflux transporters distributed at the apical side of human intestinal epithelial cells actively transport drugs from the enterocytes to the intestinal lumen, which could lead to extremely poor absorption of drugs by oral administration. Typical intestinal efflux transporters involved in oral drug absorption process mainly include P-glycoprotein (P-gp), multidrug resistance proteins (MRPs) and breast cancer resistance protein (BCRP). Drug efflux is one of the most important factors resulting in poor absorption of oral drugs. Caco-2 monolayer and everted gut sac are sued to accurately measure drug efflux in vitro. To reverse intestinal drug efflux and improve absorption of oral drugs, a great deal of functional amphiphilic excipients and inhibitors with the function of suppressing efflux transporters activity are generalized in this review. In addition, different strategies of reducing intestinal drugs efflux such as silencing transporters and the application of excipients and inhibitors are introduced. Ultimately, various nano-formulations of improving oral drug absorption by inhibiting intestinal drug efflux are discussed. In conclusion, this review has significant reference for overcoming intestinal drug efflux and improving oral drug absorption.
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.
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