Current Drug Delivery - Volume 22, Issue 7, 2025

Plant-derived extracellular vesicles (PDEVs) are vital for intercellular material exchange and information transfer. They significantly regulate cellular functions, tissue repair, and self-defense mechanisms.

This review summarizes the formation pathways, composition, and potential applications of PDEVs in anti-tumor research and drug delivery systems.

We conducted a literature search using keywords such as “plant-derived extracellular vesicles,” “exosomes,” “drug delivery,” “isolation and purification,” “stability,” “anti-tumor,” and “tumor therapy” in databases including PubMed, Web of Science, and Scopus. We examined studies on the formation pathways of PDEVs, including fusion of multivesicular bodies with the plasma membrane, exosome-positive organelles, and vacuole release. We also reviewed isolation and purification techniques critical for studying their biological functions. Furthermore, we analyzed research on the application of PDEVs in cancer therapy, focusing on their inhibitory effects in various cancer models and their role as carriers in drug delivery systems.

PDEVs have demonstrated potential in anti-tumor research, particularly with vesicles from plants like tea, garlic, and Artemisia annua showing inhibitory effects in breast, lung, and gastric cancer models. Additionally, PDEVs serve as effective carriers in drug delivery systems, offering possibilities for developing ideal therapeutic solutions.

While PDEVs show promise in cancer treatment and drug delivery, challenges such as standardization, storage stability, and elucidation of action mechanisms remain. Further research is needed to overcome these challenges and advance the clinical translation of PDEVs.

Our previous studies have found that Wumei Pills can regulate the intestinal flora to inhibit chemotherapy-induced intestinal mucositis (CIM). However, there is still insufficient evidence to confirm that intestinal flora is the main link in the regulation of CIM by Wumei Pills, and its downstream mechanism is still unclear.

We first obtained the signal pathway of the intervention of Wumei Pill on CIM through network pharmacological analysis and then transplanted the bacterial solution into CIM mice, combined with Western Blot, HE, ELISA and other biological technology-related proteins and inflammatory factors.

It showed that 97 kinds of effective ingredients and 205 kinds of targets of Wumei pills were screened out and the potential mechanism of Wumei Pills on CIM may be the NF-κB signaling pathway. In contrast with the control group, the results displayed that the weight, food intake, and mice’s colon length were apparently decreased in the 5-Fu group, while the diarrhea score was increased. However, FMT reversed this change, and the difference was statistically significant. Additionally, FMT could improve the pathological state of inflammatory cell infiltration in mice, reduce histopathological scores of colon and jejunum, decrease the expression levels of IL-1β, MPO, TNF-α, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/NF-κB and down-regulate protein expression, thereby exerting its anti-inflammatory activities. Further experiments have found that FMT could reverse the decreasing of tight junction proteins and mucins caused by 5-Fu, thereby repairing the intestinal mucosal barrier, and FMT could also increase the content of acetic acid, propanoic acid, and butanoic acid in the feces of 5-Fu group.

FMT can defend the intestinal mucosal barrier integrality by increasing the content of exercise fatty acids, and its mechanism may be in connection with its inhibition of TLR4/MyD88/NF-κB signal pathway to relieve inflammation.

Breast cancer remains a significant global health challenge, with thymoquinone showing promise as a therapeutic agent, but hindered by poor solubility.

This study aimed to enhance TQ delivery to MCF-7 breast cancer cells using mesitylene-mesoporous silica nanoparticles coated with liposomes, designed for controlled drug release.

Nanoparticles were synthesized using the sol-gel method and coated with phosphatidylserine-cholesterol liposomes. Different nanocharacterization techniques and in vitro assays were employed to assess the drug release kinetics, cellular uptake, cytotoxicity, and apoptosis.

The nanoparticles exhibited favorable properties, including a large pore size of 3.6 nm, a surface area of 248.96 m²/g, and a hydrodynamic size of 171.571 ± 8.342 nm with a polydispersity index of 0.182 ± 0.017, indicating uniformity and stability. The successful lipid bilayer coating was confirmed by a zeta potential shift from +6.25 mV to -5.65 mV. The coated nanoparticles demonstrated a slow and sustained drug release profile, with cellular uptake of FITC-formulated nanoparticles being approximately 5-fold higher than free FITC (P < 0.0001). Cytotoxicity assays revealed a significant reduction in cell viability (P < 0.0001), reaching an IC50 value of 25 µM at 48 hours. Apoptosis rates were significantly higher in cells treated with the formulated TQ compared to the free drug and control at both 24 and 48 hours (P < 0.0001).

This nanoformulation significantly enhanced TQ delivery, offering a promising strategy for targeted breast cancer therapy. Further preclinical studies are recommended to advance this approach in cancer treatment.

Cancer treatment often involves the use of potent antineoplastic drugs like Capecitabine (CAP), which can lead to serious toxicities. There is a need for dosage forms to manage these toxicities that can deliver the medication effectively to the target site while maintaining therapeutic efficacy at lower doses. To achieve the aforesaid objective, NLC containing capecitabine (NANOBIN) was prepared and evaluated. Different formulations of NANOBIN, denoted as CaTS, CaT1S, CaT2S, CaTS1, and CaTS2, were designed and evaluated to improve drug delivery and therapeutic outcomes.

The NANOBIN formulations were prepared using the hot homogenization method. The characterization of these formulations was conducted based on various parameters such as particle size, Polydispersity Index (PDI), Zeta Potential (ZP), Transmission Electron Microscopy (TEM) imaging, and Encapsulation Efficiency (EE). In vitro evaluations included stability testing, release studies to assess drug release kinetics, and a cytotoxicity assay (MTT assay) to evaluate the efficacy of these formulations against human breast cancer cells (MCF-7).

The characterization results revealed that all NANOBIN formulations exhibited particle sizes ranging from 65 to 193 nm, PDI values within the range of 0.26-0.37, ZP values between 46.47 to 61.87 mV (-ve), and high EE percentages ranging from 94.121% to 96.64%. Furthermore, all NANOBIN formulations demonstrated sustained and slow-release profiles of CAP. The MTT assay showed that the NANOBINs exhibited significantly enhanced cytotoxic efficacy, approximately 10 times greater than free CAP when tested on MCF-7 cells. These findings indicate the potential of NANOBINs to deliver CAP effectively to the target site, enabling prolonged drug availability and enhanced therapeutic effects at lower doses.

The study demonstrates that NANOBINs can effectively deliver CAP to target sites, prolonging drug exposure and enhancing therapeutic efficacy while reducing the required dose. Further studies are necessary to validate these findings and establish NANOBINs as a preferred treatment option for cancer therapy.

Alopecia is globally known as a distressing medical disorder that affects men and women, and current commercially available minoxidil solutions are formulated with irritant vehicles with frequent complaints of dermatologic adverse effects.

This study aimed to investigate further the compatibility of ready-to-use vehicles for the preparation of tailored formulations for alopecia treatment, namely TrichoSol™ (a ready-to-use vehicle for personalized hair solutions) and TrichoFoam™ (a ready-to-use vehicle for personalized foam formulations), in combination with minoxidil and other active pharmaceutical ingredients (APIs), to establish adequate beyond-use dates (BUD) for the given formulations.

Products under evaluation were compounded using TrichoSol™ or TrichoFoam™, with direct incorporation of the APIs into these vehicles. Samples were then stored at controlled room temperature for up to 180 days. High-performance liquid chromatography (HPLC) methods were developed and validated, and then utilized to evaluate the compatibility of the APIs in TrichoSol™ and TrichoFoam™. Forced degradation studies were conducted to assess API stability under various stress conditions, and Antimicrobial Effectiveness Testing (AET) was performed at 0 and 180 days after compounding.

According to our results, BUDs of up to 90-180 days were obtained for the examined formulations stored at room temperature, considering a degradation of maximum 10% of the nominal concentration of the APIs within them. The formulations exhibited no discernible physical alterations throughout this period and maintained chemical stability within acceptable limits. Microbiological evaluations confirmed the efficacy of the preservative system.

Products compounded with TrichoSol™ and TrichoFoam™ showed suitable stability to be used as personalized treatments for alopecia. We can then suggest that the vehicles TrichoSol™ and TrichoFoam™ present effective solutions for compounding personalized hair care treatments.

Fungal keratitis (mycotic keratitis) is an eye infection in which the cornea is infected by fungi and such fungal keratitis management can be effectively possible by ocular administration of antifungal drugs.

The main objectives of the present research were to develop and evaluate fluconazole-loaded transfersomal hydrogels for ocular delivery in the effective management of fungal keratitis.

A 2³ factorial design-based approach was used for statistical optimization, where (A) the ratio of lipid to edge activators, (B) the amount of hyaluronic acid (% HA), and (C) the ratio of edge activators (sodium deoxycholate to Span 80) were taken as three factors. The average vesicle diameter (Z, nm) of transfersomes was taken as a response. Further, fluconazole-loaded transfersomes (FTO) were incorporated into 1% Carbopol 940-based hydrogel (OF1) and 2% HMPC K4M-based hydrogel (OF2) containing D-panthenol (5% w/w).

The optimal variable setting for the optimized formulations of FTO was (A) = 9.15, (B) = 0.30%, and (C) = 3.00. FTO exhibited 66.39 nm Z, 0.247 polydispersity index, – 33.10 mV zeta potential, and 65.38 ± 1.77% DEE, and desirable elasticity. TEM image of FTO demonstrated a unilamellar vesicular structure. The ex vivo ocular permeation of fluconazole from transfersomal hydrogels was sustained over 24 h. All the transfersomal hydrogels showed good bioadhesion and excellent antifungal activity with respect to the zone of inhibition against Candida albicans than Aspergillus fumigates, in vitro. HET-CAM study results demonstrated that both the hydrogels were non-irritant and safe for ocular. Short-term physical stability study suggested the stability of the developed formulation.

The current research demonstrated a new way to enhance the ocular penetration of fluconazole via transfersomal hydrogel formulations for ocular delivery in the effective management of fungal keratitis.

The purpose of the study was to evaluate the suitability of mixed micelles prepared with D-α-tocopheryl polyethylene glycol succinate (TPGS) and 1,2-distearoyl-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) to encapsulate the poorly soluble anticancer drug fenretinide (4-HPR).

After assaying the solubilization ability of the surfactants by the equilibrium method, the micelles were prepared using the solvent casting technique starting from different 4-HPR:TPGS: DSPE-PEG w/w ratios. The resulting formulations were investigated for their stability under storage conditions and upon dilution, modelling the reaching of physiological concentrations after intravenous administration. The characterization of micelles included the determination of DL%, EE %, particle size distribution, Z-potential, and thermal analysis by DSC. The cytotoxicity studies were performed on HTLA-230 and SK-N-BE-2C neuroblastoma cells by the MTT essay.

The colloidal dispersions showed a mean diameter of 12 nm, negative Zeta potential, and a narrow dimensional distribution. 4-HPR was formulated in the mixed micelles with an encapsulation efficiency of 88% and with an increment of the apparent solubility of 363-fold. The 4-HPR entrapment remained stable up to the surfactants’ concentration of 2.97E-05 M. The loaded micelles exhibited a slow-release behaviour, with about 28% of the drug released after 24 h. On the most resistant SK-N-BE-2C cells, the encapsulated 4-HPR was significantly more active than free 4-HPR in reducing cell viability.

Loaded micelles demonstrated their suitability as a new adjuvant tool potentially useful for the treatment of neuroblastoma.