Rong Lu

Plant-derived nanovesicles (PDNVs) are a class of nanoscale vesicles derived from plant tissues; they are particles with a lipid bilayer and no ability to replicate autonomously. As a type of bioactive natural nanocarrier, they demonstrate immense potential for application in 21st-century nanomedicine, skincare and nutritional health, owing to their excellent biocompatibility, low immunogenicity and targeted delivery capabilities. However, the clinical translation of PDNVs still faces key bottlenecks, including low extraction efficiency, complex purification processes, and immature engineering modification techniques. Compared to the wealth of systematic reviews in the field of Mammalian Extracellular Vesicles (M-EVs), research on PDNVs still lacks a comprehensive exposition of its multifaceted research progress. This review endeavours to comprehensively summarise the shortcomings over the last 60 years regarding PDNV purification processes, research progress, composition and characterisation, engineering modifications, functional mechanisms, clinical translation and market regulation. It discusses the feasibility of innovative approaches such as AI deep learning technologies, interdisciplinary integration and cross-application, and outlines the latest frontiers in PDNV research. It provides comprehensive and reliable reference material for future research and application strategies regarding PDNVs, offering theoretical support and practical guidance to overcome barriers to their industrialisation. This will facilitate the transition from limited laboratory research to clinical application and drive technological innovation in the next generation of naturally derived nanomedicines.

In the rapidly developing field of skin care, non-surgical facial aesthetics are becoming increasingly favored by consumers. Plant-derived extracellular vesicles (PDEVs) have attracted much attention due to their low toxicity, cellular communication function, and ability to carry bioactive molecules, including proteins, lipids, nucleic acids, and small molecules with pharmacological activities. Recent in vitro studies have shown that PDEVs enhance the transdermal delivery of drugs and improve skin condition, suggesting promising applications in facial aesthetics. In this review, we provide a comprehensive overview of the application of PDEVs in anti-scarring, anti-aging, and anti-pigmentation therapies. We also discuss current limitations in their application and potential solutions to address these challenges. In conclusion, this review analyzes the roles and mechanisms of PDEVs in facial aesthetics and aims to support their future clinical application.

Cancer poses a great threat and challenge to human health. However, the most widely used chemotherapy drugs show resistance due to various reasons, such as cellular efflux, poor targeting, obvious side effects. On the other hand, as a new drug delivery vehicle, nanoparticles have attracted extensive attention due to their good targeting and low toxicity. Various nanoparticles for drug delivery, including liposomes, polymer nanoparticles, micelles, drug-polymer conjugates, dendrimers, nanoshells, magnetic nanoparticles, drug nanocrystals, and extracellular vesicles, are reviewed in this paper.

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.

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.

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 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.

Inflammatory bowel disease (IBD) is a chronic recurrent intestinal disease and includes Crohn’s disease (CD) and ulcerative colitis (UC). Due to the complex etiology of colitis, the current treatments of IBD are quite limited and are mainly concentrated on the remission of the disease. In addition, the side effects of conventional drugs on the body cannot be ignored. IBD also has a certain relationship with colitis-associated cancer (CAC), and inflammatory cells can produce a large number of tumor-promoting cytokines to promote tumor progression. In recent years, exosomes from plants have been found to have the ability to load drugs to target the intestine and have great potential for the treatment of intestinal diseases. This plant-derived exosome-targeting delivery system can load chemical or nucleic acid drugs and deliver them to intestinal inflammatory sites stably and efficiently. This review summarizes the pathophysiological characteristics of IBD and CAC as well as the application and prospect of plant exosomes in the treatment of IBD and CAC.