Advances of Membrane Vesicles in Drug Delivery Systems, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 30 May 2024 | Viewed by 12481

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Guest Editor
1. Jiangxi Key Laboratory for Microscale Interdisciplinary Study, Institute for Advanced Study, Nanchang University, Nanchang 330031, China
2. College of Life Sciences, Nanchang University, Nanchang 330031, China
Interests: lipoproteins, gangliosides, and atherosclerosis; drug delivery systems; membrane vesicles; pharmacology of cyclodextrins; fluorescent probes/sensors
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Special Issue Information

Dear Colleagues,

Drug delivery systems (DDSs) are defined as formulations or devices that deliver therapeutic substances specifically to their sites of action without reaching nontarget sites (cells, tissues, or even organs). Many benefits to drugs can be achieved by drug delivery systems, including an elevated stability, higher water solubility, prolonged circulation time, better sustained drug release, stronger tissue/cell targetability, lower drug dosage, impaired side effects, enhanced efficacy, etc. Over the last two decades, bioinspired (or biologically inspired) drug delivery systems have been intensively studied. Compared with traditional DDSs, the advantages of bioinspired DDSs include lower/no immunogenicity, biocompatibility, biodegradability, better safety, among others. By mimicking natural components inside the body, many bioinspired DDSs have been tested, including biomolecule (e.g., peptides)-, lipid-protein complex (e.g., reconstituted high-density lipoprotein)-, membrane vesicle-, virus-, and even whole cell (e.g., bacterium, erythrocyte, platelet, stem cell)-inspired DDSs. For example, membrane vesicles for drug delivery systems can be derived from different types or parts of cells, including well-known extracellular vesicles (EVs; e.g., exosomes, microvesicles or microparticles, and apoptotic bodies) released from cells, outer membrane vesicles (OMVs) from bacteria, cell-bound membrane vesicles (CBMVs) isolated in situ from cell surfaces, membrane vesicles reorganized after the isolation of the plasma membrane of cells, etc. The bearing of some specific molecules, which originally exists on/in the source cells enables membrane vesicles to have specific functions (e.g., making the target cells have some properties of the source cells). In recent years, membrane vesicle-inspired DDSs have been rapidly developed. These latest advances should be concisely summarized/reviewed, and original studies reported as soon as possible. This Special Issue of Pharmaceutics aims to collect the papers that explore the advances in membrane vesicle-based drug delivery systems.

The considered papers include, but are not limited to, the following aspects:

  • Development of methods/techniques for the isolation/preparation or characterization of membrane vesicles as drug delivery systems.
  • Evaluation of the biochemical or biophysical properties of membrane vesicles.
  • Modification of membrane vesicles for better performance.
  • Pharmacokinetics and pharmacodynamics of membrane vesicles as drug delivery systems.
  • Related mechanisms of membrane vesicle-based drug delivery systems.
  • Diagnostic, therapeutic or clinical applications of membrane vesicle-based drug delivery systems for different diseases.

Prof. Dr. Yong Chen
Guest Editor

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Published Papers (8 papers)

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Research

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15 pages, 4672 KiB  
Article
Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System
by Mena Asha Krishnan, Olawale A. Alimi, Tianshu Pan, Mitchell Kuss, Zeljka Korade, Guoku Hu, Bo Liu and Bin Duan
Pharmaceutics 2024, 16(1), 102; https://doi.org/10.3390/pharmaceutics16010102 - 12 Jan 2024
Cited by 1 | Viewed by 1682
Abstract
The administration of therapeutics to peripheral nerve tissue is challenging due to the complexities of peripheral neuroanatomy and the limitations imposed by the blood–nerve barrier (BNB). Therefore, there is a pressing need to enhance delivery effectiveness and implement targeted delivery methods. Recently, erythrocyte-derived [...] Read more.
The administration of therapeutics to peripheral nerve tissue is challenging due to the complexities of peripheral neuroanatomy and the limitations imposed by the blood–nerve barrier (BNB). Therefore, there is a pressing need to enhance delivery effectiveness and implement targeted delivery methods. Recently, erythrocyte-derived exosomes (Exos) have gained widespread attention as biocompatible vehicles for therapeutics in clinical applications. However, engineering targeted Exos for the peripheral nervous system (PNS) is still challenging. This study aims to develop a targeted Exo delivery system specifically designed for presynaptic terminals of peripheral nerve tissue. The clostridium neurotoxin, tetanus toxin-C fragment (TTC), was tethered to the surface of red blood cell (RBC)-derived Exos via a facile and efficient bio-orthogonal click chemistry method without a catalyst. Additionally, Cyanine5 (Cy5), a reactive fluorescent tag, was also conjugated to track Exo movement in both in vitro and in vivo models. Subsequently, Neuro-2a, a mouse neuronal cell line, was treated with dye-labeled Exos with/without TTC in vitro, and the results indicated that TTC-Exos exhibited more efficient accumulation along the soma and axonal circumference, compared to their unmodified counterparts. Further investigation, using a mouse model, revealed that within 72 h of intramuscular administration, engineered TTC-Exos were successfully transported into the neuromuscular junction and sciatic nerve tissues. These results indicated that TTC played a crucial role in the Exo delivery system, improving the affinity to peripheral nerves. These promising results underscore the potential of using targeted Exo carriers to deliver therapeutics for treating peripheral neuropathies. Full article
(This article belongs to the Special Issue Advances of Membrane Vesicles in Drug Delivery Systems, 2nd Edition)
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14 pages, 3462 KiB  
Article
Combining MSC Exosomes and Cerium Oxide Nanocrystals for Enhanced Dry Eye Syndrome Therapy
by Ying Tian, Yiquan Zhang, Jiawei Zhao, Fuxiao Luan, Yingjie Wang, Fan Lai, Defang Ouyang and Yong Tao
Pharmaceutics 2023, 15(9), 2301; https://doi.org/10.3390/pharmaceutics15092301 - 11 Sep 2023
Viewed by 1338
Abstract
Dry eye syndrome (DES) is a prevalent ocular disorder involving diminishe·d tear production and increased tear evaporation, leading to ocular discomfort and potential surface damage. Inflammation and reactive oxygen species (ROS) have been implicated in the pathophysiology of DES. Inflammation is one core [...] Read more.
Dry eye syndrome (DES) is a prevalent ocular disorder involving diminishe·d tear production and increased tear evaporation, leading to ocular discomfort and potential surface damage. Inflammation and reactive oxygen species (ROS) have been implicated in the pathophysiology of DES. Inflammation is one core cause of the DES vicious cycle. Moreover, there are ROS that regulate inflammation in the cycle from the upstream, which leads to treatment failure in current therapies that merely target inflammation. In this study, we developed a novel therapeutic nanoparticle approach by growing cerium oxide (Ce) nanocrystals in situ on mesenchymal stem cell-derived exosomes (MSCExos), creating MSCExo-Ce. The combined properties of MSCExos and cerium oxide nanocrystals aim to target the “inflammation-ROS-injury” pathological mechanism in DES. We hypothesized that this approach would provide a new treatment option for patients with DES. Our analysis confirmed the successful in situ crystallization of cerium onto MSCExos, and MSCExo-Ce displayed excellent biocompatibility. In vitro and in vivo experiments have demonstrated that MSCExo-Ce promotes corneal cell growth, scavenges ROS, and more effectively suppresses inflammation compared with MSCExos alone. MSCExo-Ce also demonstrated the ability to alleviate DES symptoms and reverse pathological alterations at both the cellular and tissue levels. In conclusion, our findings highlight the potential of MSCExo-Ce as a promising therapeutic candidate for the treatment of DES. Full article
(This article belongs to the Special Issue Advances of Membrane Vesicles in Drug Delivery Systems, 2nd Edition)
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14 pages, 3755 KiB  
Article
Fluorescence Tracking of Small Extracellular Vesicles In Vivo
by Yanxia Chen, Yinghong Shi and Zhimin Tao
Pharmaceutics 2023, 15(9), 2297; https://doi.org/10.3390/pharmaceutics15092297 - 8 Sep 2023
Cited by 1 | Viewed by 1316
Abstract
In this study, we employed organic and inorganic dyes that have fluorescence under visible or near-infrared light region to stain human umbilical cord (Huc) mesenchymal stem cell (MSC)-, HEK293T cell- and HGC cell-derived small extracellular vesicles (sEVs), and then tracked their fluorescence signals [...] Read more.
In this study, we employed organic and inorganic dyes that have fluorescence under visible or near-infrared light region to stain human umbilical cord (Huc) mesenchymal stem cell (MSC)-, HEK293T cell- and HGC cell-derived small extracellular vesicles (sEVs), and then tracked their fluorescence signals in human gastric cancer xenografted murine models. Several biological characteristics were examined and compared when different dye-stained sEVs in the same tumor model or the same dye-stained sEVs between different tumor models were applied, including sEVs circulation in the blood, biodistribution of sEVs in major organs, and time-dependent tumor accumulation of sEVs. The results demonstrated that distinct tumor accumulation features were presented by sEVs if labeled by different fluorescent dyes, while sEVs derived from different cell lines showed homologous blood circulation and tumor accumulation. To conclude, although fluorescence imaging remains a reliable way to trace sEVs, single staining of sEVs membrane should be obviated in future work when examining the biological fate of sEVs. Full article
(This article belongs to the Special Issue Advances of Membrane Vesicles in Drug Delivery Systems, 2nd Edition)
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Review

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23 pages, 804 KiB  
Review
Extracellular Vesicles in Breast Cancer: From Intercellular Communication to Therapeutic Opportunities
by Barathan Muttiah, Sook Luan Ng, Yogeswaran Lokanathan, Min Hwei Ng and Jia Xian Law
Pharmaceutics 2024, 16(5), 654; https://doi.org/10.3390/pharmaceutics16050654 - 14 May 2024
Viewed by 392
Abstract
Breast cancer, a multifaceted and heterogeneous disease, poses significant challenges in terms of understanding its intricate resistance mechanisms and devising effective therapeutic strategies. This review provides a comprehensive overview of the intricate landscape of extracellular vesicles (EVs) in the context of breast cancer, [...] Read more.
Breast cancer, a multifaceted and heterogeneous disease, poses significant challenges in terms of understanding its intricate resistance mechanisms and devising effective therapeutic strategies. This review provides a comprehensive overview of the intricate landscape of extracellular vesicles (EVs) in the context of breast cancer, highlighting their diverse subtypes, biogenesis, and roles in intercellular communication within the tumour microenvironment (TME). The discussion spans various aspects, from EVs and stromal cells in breast cancer to their influence on angiogenesis, immune response, and chemoresistance. The impact of EV production in different culture systems, including two dimensional (2D), three dimensional (3D), and organoid models, is explored. Furthermore, this review delves into the therapeutic potential of EVs in breast cancer, presenting emerging strategies such as engineered EVs for gene delivery, nanoplatforms for targeted chemotherapy, and disrupting tumour derived EVs as a treatment approach. Understanding these complex interactions of EV within the breast cancer milieu is crucial for identifying resistance mechanisms and developing new therapeutic targets. Full article
(This article belongs to the Special Issue Advances of Membrane Vesicles in Drug Delivery Systems, 2nd Edition)
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15 pages, 2248 KiB  
Review
Cellular-Membrane-Derived Vesicles for Cancer Immunotherapy
by Xiaoyu An, Yun Zeng, Chao Liu and Gang Liu
Pharmaceutics 2024, 16(1), 22; https://doi.org/10.3390/pharmaceutics16010022 - 22 Dec 2023
Cited by 1 | Viewed by 1256
Abstract
The medical community is constantly searching for new and innovative ways to treat cancer, and cellular-membrane-derived artificial vesicles are emerging as a promising avenue for cancer immunotherapy. These vesicles, which are derived from mammal and bacteria cell membranes, offer a range of benefits, [...] Read more.
The medical community is constantly searching for new and innovative ways to treat cancer, and cellular-membrane-derived artificial vesicles are emerging as a promising avenue for cancer immunotherapy. These vesicles, which are derived from mammal and bacteria cell membranes, offer a range of benefits, including compatibility with living organisms, minimal immune response, and prolonged circulation. By modifying their surface, manipulating their genes, combining them with other substances, stimulating them externally, and even enclosing drugs within them, cellular vesicles have the potential to be a powerful tool in fighting cancer. The ability to merge drugs with diverse compositions and functionalities in a localized area is particularly exciting, as it offers a way to combine different immunotherapy treatments for maximum impact. This review contains information on the various sources of these vesicles and discusses some recent developments in cancer immunotherapy using this promising technology. While there are still obstacles to overcome, the possibilities for cellular vesicles in cancer treatment are truly exciting. Full article
(This article belongs to the Special Issue Advances of Membrane Vesicles in Drug Delivery Systems, 2nd Edition)
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20 pages, 1630 KiB  
Review
Mesenchymal Stromal Cells-Derived Extracellular Vesicles as Potential Treatments for Osteoarthritis
by Shunling Yuan, Guangfeng Li, Jinbo Zhang, Xiao Chen, Jiacan Su and Fengjin Zhou
Pharmaceutics 2023, 15(7), 1814; https://doi.org/10.3390/pharmaceutics15071814 - 25 Jun 2023
Cited by 1 | Viewed by 1468
Abstract
Osteoarthritis (OA) is a degenerative disease of the joints characterized by cartilage damage and severe pain. Despite various pharmacological and surgical interventions, current therapies fail to halt OA progression, leading to high morbidity and an economic burden. Thus, there is an urgent need [...] Read more.
Osteoarthritis (OA) is a degenerative disease of the joints characterized by cartilage damage and severe pain. Despite various pharmacological and surgical interventions, current therapies fail to halt OA progression, leading to high morbidity and an economic burden. Thus, there is an urgent need for alternative therapeutic approaches that can effectively address the underlying pathophysiology of OA. Extracellular Vesicles (EVs) derived from mesenchymal stromal cells (MSCs) represent a new paradigm in OA treatment. MSC-EVs are small membranous particles released by MSCs during culture, both in vitro and in vivo. They possess regenerative properties and can attenuate inflammation, thereby promoting cartilage healing. Importantly, MSC-EVs have several advantages over MSCs as cell-based therapies, including lower risks of immune reactions and ethical issues. Researchers have recently explored different strategies, such as modifying EVs to enhance their delivery, targeting efficiency, and security, with promising results. This article reviews how MSC-EVs can help treat OA and how they might work. It also briefly discusses the benefits and challenges of using MSC-EVs and talks about the possibility of allogeneic and autologous MSC-EVs for medical use. Full article
(This article belongs to the Special Issue Advances of Membrane Vesicles in Drug Delivery Systems, 2nd Edition)
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21 pages, 1841 KiB  
Review
Naïve or Engineered Extracellular Vesicles from Different Cell Sources: Therapeutic Tools for Kidney Diseases
by Elena Ceccotti, Gabriele Saccu, Maria Beatriz Herrera Sanchez and Stefania Bruno
Pharmaceutics 2023, 15(6), 1715; https://doi.org/10.3390/pharmaceutics15061715 - 12 Jun 2023
Cited by 5 | Viewed by 1527
Abstract
Renal pathophysiology is a multifactorial process involving different kidney structures. Acute kidney injury (AKI) is a clinical condition characterized by tubular necrosis and glomerular hyperfiltration. The maladaptive repair after AKI predisposes to the onset of chronic kidney diseases (CKD). CKD is a progressive [...] Read more.
Renal pathophysiology is a multifactorial process involving different kidney structures. Acute kidney injury (AKI) is a clinical condition characterized by tubular necrosis and glomerular hyperfiltration. The maladaptive repair after AKI predisposes to the onset of chronic kidney diseases (CKD). CKD is a progressive and irreversible loss of kidney function, characterized by fibrosis that could lead to end stage renal disease. In this review we provide a comprehensive overview of the most recent scientific publications analyzing the therapeutic potential of Extracellular Vesicles (EV)-based treatments in different animal models of AKI and CKD. EVs from multiple sources act as paracrine effectors involved in cell-cell communication with pro-generative and low immunogenic properties. They represent innovative and promising natural drug delivery vehicles used to treat experimental acute and chronic kidney diseases. Differently from synthetic systems, EVs can cross biological barriers and deliver biomolecules to the recipient cells inducing a physiological response. Moreover, new methods for improving the EVs as carriers have been introduced, such as the engineering of the cargo, the modification of the proteins on the external membrane, or the pre-conditioning of the cell of origin. The new nano-medicine approaches based on bioengineered EVs are an attempt to enhance their drug delivery capacity for potential clinical applications. Full article
(This article belongs to the Special Issue Advances of Membrane Vesicles in Drug Delivery Systems, 2nd Edition)
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19 pages, 1759 KiB  
Review
Extracellular Vesicles and Intercellular Communication: Challenges for In Vivo Molecular Imaging and Tracking
by Debora Petroni, Costanza Fabbri, Serena Babboni, Luca Menichetti, Giuseppina Basta and Serena Del Turco
Pharmaceutics 2023, 15(6), 1639; https://doi.org/10.3390/pharmaceutics15061639 - 1 Jun 2023
Cited by 6 | Viewed by 1858
Abstract
Extracellular vesicles (EVs) are a heterogeneous class of cell-derived membrane vesicles released by various cell types that serve as mediators of intercellular signaling. When released into circulation, EVs may convey their cargo and serve as intermediaries for intracellular communication, reaching nearby cells and [...] Read more.
Extracellular vesicles (EVs) are a heterogeneous class of cell-derived membrane vesicles released by various cell types that serve as mediators of intercellular signaling. When released into circulation, EVs may convey their cargo and serve as intermediaries for intracellular communication, reaching nearby cells and possibly also distant organs. In cardiovascular biology, EVs released by activated or apoptotic endothelial cells (EC-EVs) disseminate biological information at short and long distances, contributing to the development and progression of cardiovascular disease and related disorders. The significance of EC-EVs as mediators of cell–cell communication has advanced, but a thorough knowledge of the role that intercommunication plays in healthy and vascular disease is still lacking. Most data on EVs derive from in vitro studies, but there are still little reliable data available on biodistribution and specific homing EVs in vivo tissues. Molecular imaging techniques for EVs are crucial to monitoring in vivo biodistribution and the homing of EVs and their communication networks both in basal and pathological circumstances. This narrative review provides an overview of EC–EVs, trying to highlight their role as messengers of cell–cell interaction in vascular homeostasis and disease, and describes emerging applications of various imaging modalities for EVs visualization in vivo. Full article
(This article belongs to the Special Issue Advances of Membrane Vesicles in Drug Delivery Systems, 2nd Edition)
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