Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
6.9
5.4
Journals
Pharmaceutics
Special Issues
Extracellular Vesicles as Drug Delivery Systems
share announcement

Extracellular Vesicles as Drug Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: closed (20 November 2021) | Viewed by 42506

Special Issue Editor

Dr. Lorena Urbanelli

E-Mail Website
Guest Editor
Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, Italy
Interests: extracellular vesicles; autophagy; lysosomes; senescence; aging; lipidomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There is growing interest for extracellular vesicles (EVs) as tools for drug delivery. EVs are membrane vesicles released in cell medium and retrieved in every fluid of the body, representing a mean not only for the disposal of unwanted material, but also for cell communication. The discovery that EVs carry nucleic acids, mostly ncRNA but also mRNA, has demonstrated that they can be considered a mean of horizontal gene transfer. EVs are relatively stable in circulating body fluids as compared to synthetic lipid nanoparticles, and they can overcome natural barriers. These features have opened new perspectives for the use of EVs as drug delivery vehicles, including gene delivery. EVs from different sources have been loaded with drugs and nucleic acids. However, there are safety issues to solve and methodological problems to fix about EV isolation from different sources, separation from contaminants, and loading with drugs. In addition, molecular mechanisms underlying their targeting ability and circulation stability are far from being elucidated. The aim of this Issue of Pharmaceutics is to collect research and review articles dealing with the use of EVs for drug delivery. We welcome articles dealing with all aspects of this field and invite researchers to publish their results as well as to contribute to the discussion on the development of EVs as drug delivery vehicles.

Dr. Lorena Urbanelli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Extracellular vesicles
  • Exosomes
  • Microvesicles
  • Drug delivery
  • Vesicles targeting
  • Vesicles loading
  • Vesicles separation
  • Vesicles uptake
  • Gene therapy

Published Papers (10 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

13 pages, 2806 KiB  
Article
Dual-Targeted Extracellular Vesicles to Facilitate Combined Therapies for Neuroendocrine Cancer Treatment
by Yingnan Si, JiaShiung Guan, Yuanxin Xu, Kai Chen, Seulhee Kim, Lufang Zhou, Renata Jaskula-Sztul and X. Margaret Liu
Pharmaceutics 2020, 12(11), 1079; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12111079 - 11 Nov 2020
Cited by 13 | Viewed by 3175
Abstract
Neuroendocrine (NE) cancers arise from cells within the neuroendocrine system. Chemotherapies and endoradiotherapy have been developed, but their clinical efficacy is limited. The objective of this study was to develop a dual-targeted extracellular vesicles (EV)-delivered combined therapies to treat NE cancer. Specifically, we [...] Read more.
Neuroendocrine (NE) cancers arise from cells within the neuroendocrine system. Chemotherapies and endoradiotherapy have been developed, but their clinical efficacy is limited. The objective of this study was to develop a dual-targeted extracellular vesicles (EV)-delivered combined therapies to treat NE cancer. Specifically, we produced EV in stirred-tank bioreactors and surface tagged both anti-somatostatin receptor 2 (SSTR 2) monoclonal antibody (mAb) and anti-C-X-C motif chemokine receptor 4 (CXCR4) mAb to generate mAbs-EV. Both live-cell confocal microscopy imaging and In Vivo Imaging System (IVIS) imaging confirmed that mAbs-EV specifically targeted and accumulated in NE cancer cells and NE tumor xenografts. Then the highly potent natural cytotoxic marine compound verrucarin A (Ver-A) with IC50 of 2.2–2.8 nM and microtubule polymerization inhibitor mertansine (DM1) with IC50 of 3.1–4.2 nM were packed into mAbs-EV. The in vivo maximum tolerated dose study performed in non-tumor-bearing mice indicated minimal systemic toxicity of mAbs-EV-Ver-A/DM1. Finally, the in vivo anticancer efficacy study demonstrated that the SSTR2/CXCR4 dual-targeted EV-Ver-A/DM1 is more effective to inhibit NE tumor growth than the single targeting and single drug. The results from this study could expand the application of EV to targeting deliver the combined potent chemotherapies for cancer treatment. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Graphical abstract

17 pages, 3517 KiB  
Article
Low-Vacuum Filtration as an Alternative Extracellular Vesicle Concentration Method: A Comparison with Ultracentrifugation and Differential Centrifugation
by Anna Drożdż, Agnieszka Kamińska, Magdalena Surman, Agnieszka Gonet-Surówka, Robert Jach, Hubert Huras, Małgorzata Przybyło and Ewa Łucja Stępień
Pharmaceutics 2020, 12(9), 872; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12090872 - 13 Sep 2020
Cited by 12 | Viewed by 4081
Abstract
Recent years have brought great focus on the development of drug delivery systems based on extracellular vesicles (EVs). Considering the possible applications of EVs as drug carriers, the isolation process is a crucial step. To solve the problems involved in EV isolation, we [...] Read more.
Recent years have brought great focus on the development of drug delivery systems based on extracellular vesicles (EVs). Considering the possible applications of EVs as drug carriers, the isolation process is a crucial step. To solve the problems involved in EV isolation, we developed and validated a new EV isolation method—low-vacuum filtration (LVF)—and compared it with two commonly applied procedures—differential centrifugation (DC) and ultracentrifugation (UC). EVs isolated from endothelial cell culture media were characterized by (a) Transmission Electron Microscopy (TEM), (b) Nanoparticle Tracking Analysis (NTA), (c) Western blot and (d) Attenuated Total Reflection Fourier-Transform Infrared Spectroscopy (ATR-FTIR). Additionally, the membrane surface was imaged with Environmental Scanning Electron Microscopy (ESEM). We found that LVF was a reproducible and efficient method for EV isolation from conditioned media. Additionally, we observed a correlation between ATR-FTIR spectra quality and EV and protein concentration. ESEM imaging confirmed that the actual pore diameter was close to the values calculated theoretically. LVF is an easy, fast and inexpensive EV isolation method that allows for the isolation of both ectosomes and exosomes from high-volume sources with good repeatability. We believe that it could be an efficient alternative to commonly applied methods. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Figure 1

Review

Jump to: Research

21 pages, 3655 KiB  
Review
Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine
by Mariaevelina Alfieri, Antonietta Leone and Alfredo Ambrosone
Pharmaceutics 2021, 13(4), 498; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13040498 - 06 Apr 2021
Cited by 49 | Viewed by 5130
Abstract
Plants produce different types of nano and micro-sized vesicles. Observed for the first time in the 60s, plant nano and microvesicles (PDVs) and their biological role have been inexplicably under investigated for a long time. Proteomic and metabolomic approaches revealed that PDVs carry [...] Read more.
Plants produce different types of nano and micro-sized vesicles. Observed for the first time in the 60s, plant nano and microvesicles (PDVs) and their biological role have been inexplicably under investigated for a long time. Proteomic and metabolomic approaches revealed that PDVs carry numerous proteins with antifungal and antimicrobial activity, as well as bioactive metabolites with high pharmaceutical interest. PDVs have also been shown to be also involved in the intercellular transfer of small non-coding RNAs such as microRNAs, suggesting fascinating mechanisms of long-distance gene regulation and horizontal transfer of regulatory RNAs and inter-kingdom communications. High loading capacity, intrinsic biological activities, biocompatibility, and easy permeabilization in cell compartments make plant-derived vesicles excellent natural or bioengineered nanotools for biomedical applications. Growing evidence indicates that PDVs may exert anti-inflammatory, anti-oxidant, and anticancer activities in different in vitro and in vivo models. In addition, clinical trials are currently in progress to test the effectiveness of plant EVs in reducing insulin resistance and in preventing side effects of chemotherapy treatments. In this review, we concisely introduce PDVs, discuss shortly their most important biological and physiological roles in plants and provide clues on the use and the bioengineering of plant nano and microvesicles to develop innovative therapeutic tools in nanomedicine, able to encompass the current drawbacks in the delivery systems in nutraceutical and pharmaceutical technology. Finally, we predict that the advent of intense research efforts on PDVs may disclose new frontiers in plant biotechnology applied to nanomedicine. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Figure 1

28 pages, 2370 KiB  
Review
Exosomes as Drug Delivery Systems: Endogenous Nanovehicles for Treatment of Systemic Lupus Erythematosus
by Ana Ortega, Olga Martinez-Arroyo, Maria J. Forner and Raquel Cortes
Pharmaceutics 2021, 13(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13010003 - 22 Dec 2020
Cited by 49 | Viewed by 5875
Abstract
Exosomes, nanometer-sized lipid-bilayer-enclosed extracellular vesicles (EVs), have attracted increasing attention due to their inherent ability to shuttle proteins, lipids and genes between cells and their natural affinity to target cells. Their intrinsic features such as stability, biocompatibility, low immunogenicity and ability to overcome [...] Read more.
Exosomes, nanometer-sized lipid-bilayer-enclosed extracellular vesicles (EVs), have attracted increasing attention due to their inherent ability to shuttle proteins, lipids and genes between cells and their natural affinity to target cells. Their intrinsic features such as stability, biocompatibility, low immunogenicity and ability to overcome biological barriers, have prompted interest in using exosomes as drug delivery vehicles, especially for gene therapy. Evidence indicates that exosomes play roles in both immune stimulation and tolerance, regulating immune signaling and inflammation. To date, exosome-based nanocarriers delivering small molecule drugs have been developed to treat many prevalent autoimmune diseases. This review highlights the key features of exosomes as drug delivery vehicles, such as therapeutic cargo, use of targeting peptide, loading method and administration route with a broad focus. In addition, we outline the current state of evidence in the field of exosome-based drug delivery systems in systemic lupus erythematosus (SLE), evaluating exosomes derived from various cell types and engineered exosomes. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Figure 1

25 pages, 24313 KiB  
Review
Exploiting the Natural Properties of Extracellular Vesicles in Targeted Delivery towards Specific Cells and Tissues
by Pablo Lara, Alan B. Chan, Luis J. Cruz, Andrew F. G. Quest and Marcelo J. Kogan
Pharmaceutics 2020, 12(11), 1022; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12111022 - 26 Oct 2020
Cited by 32 | Viewed by 3660
Abstract
Extracellular vesicles (EVs) are important mediators of intercellular communication that participate in many physiological/pathological processes. As such, EVs have unique properties related to their origin, which can be exploited for drug delivery applications in cell regeneration, immunosuppression, inflammation, cancer treatment or cardioprotection. Moreover, [...] Read more.
Extracellular vesicles (EVs) are important mediators of intercellular communication that participate in many physiological/pathological processes. As such, EVs have unique properties related to their origin, which can be exploited for drug delivery applications in cell regeneration, immunosuppression, inflammation, cancer treatment or cardioprotection. Moreover, their cell-like membrane organization facilitates uptake and accumulation in specific tissues and organs, which can be exploited to improve selectivity of cargo delivery. The combination of these properties with the inclusion of drugs or imaging agents can significantly improve therapeutic efficacy and selectivity, reduce the undesirable side effects of drugs or permit earlier diagnosis of diseases. In this review, we will describe the natural properties of EVs isolated from different cell sources and discuss strategies that can be applied to increase the efficacy of targeting drugs or other contents to specific locations. The potential risks associated with the use of EVs will also be addressed. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Graphical abstract

37 pages, 1260 KiB  
Review
Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine
by Bart de Jong, Eric Raul Barros, Joost G. J. Hoenderop and Juan Pablo Rigalli
Pharmaceutics 2020, 12(11), 1006; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12111006 - 22 Oct 2020
Cited by 33 | Viewed by 5218
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Graphical abstract

18 pages, 925 KiB  
Review
Extracellular Vesicle-Based Nucleic Acid Delivery: Current Advances and Future Perspectives in Cancer Therapeutic Strategies
by Crescenzo Massaro, Giulia Sgueglia, Victoria Frattolillo, S. Rubina Baglio, Lucia Altucci and Carmela Dell'Aversana
Pharmaceutics 2020, 12(10), 980; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12100980 - 16 Oct 2020
Cited by 24 | Viewed by 3422
Abstract
Extracellular vesicles (EVs) are sophisticated and sensitive messengers released by cells to communicate with and influence distant and neighboring cells via selective transfer of bioactive content, including protein lipids and nucleic acids. EVs have therefore attracted broad interest as new and refined potential [...] Read more.
Extracellular vesicles (EVs) are sophisticated and sensitive messengers released by cells to communicate with and influence distant and neighboring cells via selective transfer of bioactive content, including protein lipids and nucleic acids. EVs have therefore attracted broad interest as new and refined potential therapeutic systems in many diseases, including cancer, due to their low immunogenicity, non-toxicity, and elevated bioavailability. They might serve as safe and effective vehicles for the transport of therapeutic molecules to specific tissues and cells. In this review, we focus on EVs as a vehicle for gene therapy in cancer. We describe recent developments in EV engineering to achieve efficient intracellular delivery of cancer therapeutics and avoid off-target effects, to provide an overview of the potential applications of EV-mediated gene therapy and the most promising biomedical advances. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Graphical abstract

17 pages, 1164 KiB  
Review
Lead Compounds in the Context of Extracellular Vesicle Research
by Thao T.D. Tran and Phuong H.L. Tran
Pharmaceutics 2020, 12(8), 716; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12080716 - 30 Jul 2020
Cited by 2 | Viewed by 3038
Abstract
Studies of small extracellular vesicles (sEVs), known as exosomes, have been flourishing in the last decade with several achievements, from advancing biochemical knowledge to use in biomedical applications. Physiological changes of sEVs due to the variety of cargos they carry undoubtedly leave an [...] Read more.
Studies of small extracellular vesicles (sEVs), known as exosomes, have been flourishing in the last decade with several achievements, from advancing biochemical knowledge to use in biomedical applications. Physiological changes of sEVs due to the variety of cargos they carry undoubtedly leave an impression that affects the understanding of the mechanism underlying disease and the development of sEV-based shuttles used for treatments and non-invasive diagnostic tools. Indeed, the remarkable properties of sEVs are based on their nature, which helps shield them from recognition by the immune system, protects their payload from biochemical degradation, and contributes to their ability to translocate and convey information between cells and their inherent ability to target disease sites such as tumors that is valid for sEVs derived from cancer cells. However, their transport, biogenesis, and secretion mechanisms are still not thoroughly clear, and many ongoing investigations seek to determine how these processes occur. On the other hand, lead compounds have been playing critical roles in the drug discovery process and have been recently employed in studies of the biogenesis and secretion of sEVs as external agents, affecting sEV release and serving as drug payloads in sEV drug delivery systems. This article gives readers an overview of the roles of lead compounds in these two research areas of sEVs, the rising star in studies of nanoscale medicine. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Figure 1

19 pages, 3469 KiB  
Review
Development of New Strategies Using Extracellular Vesicles Loaded with Exogenous Nucleic Acid
by Nicola Salvatore Orefice
Pharmaceutics 2020, 12(8), 705; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12080705 - 26 Jul 2020
Cited by 33 | Viewed by 3855
Abstract
Gene therapy is a therapeutic strategy of delivering foreign genetic material (encoding for an important protein) into a patient’s target cell to replace a defective gene. Nucleic acids are embedded within the adeno-associated virus (AAVs) vectors; however, preexisting immunity to AAVs remains a [...] Read more.
Gene therapy is a therapeutic strategy of delivering foreign genetic material (encoding for an important protein) into a patient’s target cell to replace a defective gene. Nucleic acids are embedded within the adeno-associated virus (AAVs) vectors; however, preexisting immunity to AAVs remains a significant concern that impairs their clinical application. Extracellular vesicles (EVs) hold great potential for therapeutic applications as vectors of nucleic acids due to their endogenous intercellular communication functions through their cargo delivery, including lipids and proteins. So far, small RNAs (siRNA and micro (mi)RNA) have been mainly loaded into EVs to treat several diseases, but the potential use of EVs to load and deliver exogenous plasmid DNA has not been thoroughly described. This review provides a comprehensive overview of the principal methodologies currently employed to load foreign genetic material into EVs, highlighting the need to find the most effective strategies for their successful clinical translation. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Figure 1

17 pages, 1609 KiB  
Review
Engineered Extracellular Vesicles/Exosomes as a New Tool against Neurodegenerative Diseases
by Flavia Ferrantelli, Chiara Chiozzini, Patrizia Leone, Francesco Manfredi and Maurizio Federico
Pharmaceutics 2020, 12(6), 529; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12060529 - 09 Jun 2020
Cited by 9 | Viewed by 3921
Abstract
Neurodegenerative diseases are commonly generated by intracellular accumulation of misfolded/aggregated mutated proteins. These abnormal protein aggregates impair the functions of mitochondria and induce oxidative stress, thereby resulting in neuronal cell death. In turn, neuronal damage induces chronic inflammation and neurodegeneration. Thus, reducing/eliminating these [...] Read more.
Neurodegenerative diseases are commonly generated by intracellular accumulation of misfolded/aggregated mutated proteins. These abnormal protein aggregates impair the functions of mitochondria and induce oxidative stress, thereby resulting in neuronal cell death. In turn, neuronal damage induces chronic inflammation and neurodegeneration. Thus, reducing/eliminating these abnormal protein aggregates is a priority for any anti-neurodegenerative therapeutic approach. Although several antibodies against mutated neuronal proteins have been already developed, how to efficiently deliver them inside the target cells remains an unmet issue. Extracellular vesicles/exosomes incorporating intrabodies against the pathogenic products would be a tool for innovative therapeutic approaches. In this review/perspective article, we identify and describe the major molecular targets associated with neurodegenerative diseases, as well as the antibodies already developed against them. Finally, we propose a novel targeting strategy based on the endogenous engineering of extracellular vesicles/exosomes constitutively released by cells of the central nervous system. Full article
(This article belongs to the Special Issue Extracellular Vesicles as Drug Delivery Systems)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-10
Back to TopTop