Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Extracellular Vesicles as Natural, Safe and Efficient Drug Delivery Systems.

ABSTRACT: Extracellular vesicles (EVs) are particles naturally released from cells, delimited by a lipid bilayer, carrying functionally active biological molecules. In addition to their physiological role in cellular communication, the interest of the scientific community has recently turned to the use of EVs as vehicles for delivering therapeutic molecules. Several attempts are being made to ameliorate drug encapsulation and targeting, but these efforts are thwarted if the starting material does not meet stringent quality criteria. Here, we take a step back to the sources and isolation procedures that could guarantee significant improvements in the purification of EVs to be used as drug carriers, highlighting the advantages and shortcomings of each approach.

SUBMITTER: Villa F

PROVIDER: S-EPMC6920944 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Extracellular Vesicles as Natural, Safe and Efficient Drug Delivery Systems.

Villa Federico F Quarto Rodolfo R Tasso Roberta R

Pharmaceutics 20191028 11

Extracellular vesicles (EVs) are particles naturally released from cells, delimited by a lipid bilayer, carrying functionally active biological molecules. In addition to their physiological role in cellular communication, the interest of the scientific community has recently turned to the use of EVs as vehicles for delivering therapeutic molecules. Several attempts are being made to ameliorate drug encapsulation and targeting, but these efforts are thwarted if the starting material does not meet ...[more]

PMID: 31661862

Similar Datasets

Extracellular Vesicles as Drug Delivery Systems in Cancer.

Project description:Within tumors, Cancer Stem Cell (CSC) subpopulation has an important role in maintaining growth and dissemination while preserving high resistance against current treatments. It has been shown that, when CSCs are eliminated, the surrounding Differentiated Cancer Cells (DCCs) may reverse their phenotype and gain CSC-like features to preserve tumor progression and ensure tumor survival. This strongly suggests the existence of paracrine communication within tumor cells. It is evidenced that the molecular crosstalk is at least partly mediated by Extracellular Vesicles (EVs), which are cell-derived membranous nanoparticles that contain and transport complex molecules that can affect and modify the biological behavior of distal cells and their molecular background. This ability of directional transport of small molecules prospects EVs as natural Drug Delivery Systems (DDS). EVs present inherent homing abilities and are less immunogenic than synthetic nanoparticles, in general. Currently, strong efforts are focused into the development and improvement of EV-based DDS. Even though EV-DDS have already reached early phases in clinical trials, their clinical application is still far from commercialization since protocols for EVs loading, modification and isolation need to be standardized for large-scale production. Here, we summarized recent knowledge regarding the use of EVs as natural DDS against CSCs and cancer resistance.

| S-EPMC7761384 | biostudies-literature

Efficient RNA drug delivery using red blood cell extracellular vesicles.

Project description:Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR-Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.

| S-EPMC6004015 | biostudies-literature

Extracellular Nanovesicles: From Intercellular Messengers to Efficient Drug Delivery Systems.

Project description:Nanosized extracellular vesicles (nEV) are released by all the eukaryotic cells into the extracellular spaces. They serve as crucial mediators of intercellular communication, and their presence has been detected in a variety of body fluids. nEV carry nucleic acids, lipids, proteins, and metabolites from the donor cells and transfer them to the recipient cells in the vicinity or distant locations to cause changes in their biological phenotypes. This very property of nEV makes them a suitable carrier of the drugs for therapeutic applications. The use of nEV as a drug delivery system offers several advantages over synthetic nanoparticles, including biocompatibility, natural targeting ability, and long-term safety. Further, nEV can be isolated from various biological sources, quickly loaded with the drug of choice, and modified to further enhance their utility as targeted drug delivery vehicles. Here we review these aspects of nEV and discuss the parameters that should be kept in mind while choosing the nEV source, drug loading method, and surface modification strategies. We also discuss the challenges associated with the nEV-based drug delivery platforms that must be overcome before realizing their full potential in clinical applications.

| S-EPMC7841770 | biostudies-literature

Engineered extracellular vesicles as versatile ribonucleoprotein delivery vehicles for efficient and safe CRISPR genome editing.

Project description:Transient delivery of CRISPR-based genome editing effectors is important to reduce off-target effects and immune responses. Recently extracellular vesicles (EVs) have been explored for Cas9 ribonucleoprotein (RNP) delivery. However, lack of mechanisms to enrich RNPs into EVs limited the efficiency of EVs as a RNP delivery vehicle. Here we describe a mechanism to actively enrich RNPs into EVs. We used the specific interaction between RNA aptamer and aptamer-binding protein (ABP) to enrich RNPs into EVs. We inserted RNA aptamer com into single guide RNA (sgRNA), and fused com-binding ABP Com to both termini of tetraspan protein CD63 that is abundant in exosomes. We found that the Com/com interaction enriched Cas9 and adenine base editor (ABE) RNPs into EVs, via forming a three-component complex including CD63-Com fusion protein, com-modified sgRNA and Cas9 or ABE. The RNP enriched EVs are efficient in genome editing and transiently expressed. The system is capable of delivering RNPs targeting multiple loci for multiplex genome editing. In addition, Cas9 from different species can be used together. The EV-delivered RNPs are active in vivo. The data show that the aptamer and ABP interactions can be utilized to actively enrich RNPs into EVs for improved genome editing efficiency and safety.

| S-EPMC7962171 | biostudies-literature

Extracellular Vesicles as Drug Delivery Systems in Organ Transplantation: The Next Frontier.

Project description:Extracellular vesicles are lipid bilayer-delimited nanoparticles excreted into the extracellular space by all cells. They carry a cargo rich in proteins, lipids and DNA, as well as a full complement of RNA species, which they deliver to recipient cells to induce downstream signalling, and they play a key role in many physiological and pathological processes. There is evidence that native and hybrid EVs may be used as effective drug delivery systems, with their intrinsic ability to protect and deliver a functional cargo by utilising endogenous cellular mechanisms making them attractive as therapeutics. Organ transplantation is the gold standard for treatment for suitable patients with end-stage organ failure. However, significant challenges still remain in organ transplantation; prevention of graft rejection requires heavy immunosuppression and the lack of donor organs results in a failure to meet demand, as manifested by growing waiting lists. Pre-clinical studies have demonstrated the ability of EVs to prevent rejection in transplantation and mitigate ischemia reperfusion injury in several disease models. The findings of this work have made clinical translation of EVs possible, with several clinical trials actively recruiting patients. However, there is much to be uncovered, and it is essential to understand the mechanisms behind the therapeutic benefits of EVs. Machine perfusion of isolated organs provides an unparalleled platform for the investigation of EV biology and the testing of the pharmacokinetic and pharmacodynamic properties of EVs. This review classifies EVs and their biogenesis routes, and discusses the isolation and characterisation methods adopted by the international EV research community, before delving into what is known about EVs as drug delivery systems and why organ transplantation represents an ideal platform for their development as drug delivery systems.

| S-EPMC10052210 | biostudies-literature

Extracellular vesicles: Natural liver-accumulating drug delivery vehicles for the treatment of liver diseases.

Project description:Extracellular vesicles (EVs) are excellent potential vectors for the delivery of therapeutic drugs. However, issues with biological safety and disease targeting substantially limit their clinical application. EVs from red blood cells (RBC-EVs) are potential drug delivery vehicles because of their unique biological safety. Here, we demonstrated that EVs, including RBC-EVs, show natural liver accumulation. Mechanistically, the liver environment induces macrophages to phagocytize RBC-EVs in a C1q-dependent manner. RBC-EVs loaded with antisense oligonucleotides of microRNA-155 showed macrophage-dependent protective effects against acute liver failure (ALF) in a mouse model. These RBC-EVs were also effective in treatment of ALF. Furthermore, compared to routine doses of doxorubicin and sorafenib (SRF), RBC-EVs loaded with doxorubicin or SRF showed enhanced therapeutic effects on a murine model of orthotopic liver cancer through a mechanism dependent on macrophages. Importantly, drug-loaded RBC-EVs showed no systemic toxicity at therapeutically effective doses, whereas routine doses of doxorubicin and SRF showed obvious toxicity. Thus, drug-loaded RBC-EVs hold high potential for clinical applications in the treatment of liver disease therapy.

| S-EPMC7726052 | biostudies-literature

Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine.

Project description:Extracellular vesicles (EVs) are membrane-bilayered nanoparticles released by most cell types. Recently, an enormous number of studies have been published on the potential of EVs as carriers of therapeutic agents. In contrast to systems such as liposomes, EVs exhibit less immunogenicity and higher engineering potential. Here, we review the most relevant publications addressing the potential and use of EVs as a drug delivery system (DDS). The information is divided based on the key steps for designing an EV-mediated delivery strategy. We discuss possible sources and isolation methods of EVs. We address the administration routes that have been tested in vivo and the tissue distribution observed. We describe the current knowledge on EV clearance, a significant challenge towards enhancing bioavailability. Also, EV-engineering approaches are described as alternatives to improve tissue and cell-specificity. Finally, a summary of the ongoing clinical trials is performed. Although the application of EVs in the clinical practice is still at an early stage, a high number of studies in animals support their potential as DDS. Thus, better treatment options could be designed to precisely increase target specificity and therapeutic efficacy while reducing off-target effects and toxicity according to the individual requirements of each patient.

| S-EPMC7690579 | biostudies-literature

Extracellular Vesicles for Drug Delivery in Cancer Treatment.

Project description:Extracellular vesicles (EVs) are nanoscale vesicles derived from cells that mediate intercellular communication by transporting bioactive molecules. They play significant roles in various physiological and pathological conditions. EVs hold great potential as novel biomarkers of diseases, therapeutic agents, and drug delivery vehicles. Furthermore, EVs as novel drug delivery vehicles have demonstrated significant advantages in preclinical settings. In this review, we discussed the biogenesis and characteristics of EVs and their functions in cancer. We summarize the therapeutic applications of EVs as a natural delivery vehicles in cancer therapy. We highlight the existing challenges, illuminate vital questions, and propose recommendations to effectively address them effectively.

| S-EPMC10634104 | biostudies-literature

Cow Milk and Intestinal Epithelial Cell-derived Extracellular Vesicles as Systems for Enhancing Oral Drug Delivery.

Project description:Ingestion is the preferred way for drug administration. However, many drugs have poor oral bioavailability, warranting the use of injections. Extracellular vesicles (EVs) from cow milk have shown potential utility in improving oral drug bioavailability. However, EVs produced by intestinal epithelial cells have not been investigated for this application. We compared the capacity of cow milk EVs and intestinal epithelial cell-derived counterparts to enhance oral drug bioavailability. EVs were isolated, fluorescently labelled, and loaded with curcumin (CUR) as a model poorly absorbable drug. These were then characterised before testing in an intestinal model (Caco-2). Epithelial cell-derived EVs showed notably higher cell uptake compared to cow milk EVs. Cell uptake was significantly higher in differentiated compared to undifferentiated cells for both types of EVs. While both milk- and cell-derived EVs improved the cell uptake and intestinal permeability of CUR (confirming oral drug bioavailability enhancement potential), epithelial cell EVs demonstrated a superior effect.

| S-EPMC7150822 | biostudies-literature

Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma.

Project description:Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.

| S-EPMC7432055 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data