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

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.

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Therapeutic Potential of Extracellular Vesicles in Hypertension-Associated Kidney Disease

Hypertension ◽

10.1161/hypertensionaha.120.16064 ◽

2021 ◽

Vol 77 (1) ◽

pp. 28-38

Author(s):

Olga Martinez-Arroyo ◽

Ana Ortega ◽

Josep Redon ◽

Raquel Cortes

Keyword(s):

Kidney Disease ◽

Extracellular Vesicles ◽

Renal Damage ◽

Therapeutic Potential ◽

Cell Communication ◽

Cell Types ◽

Organ Damage ◽

Renal Diseases ◽

Biological Processes ◽

Potential Use

Hypertension-mediated organ damage frequently includes renal function decline in which several mechanisms are involved. The present review outlines the state of the art on extracellular vesicles in hypertension and hypertension-related renal damage. Emerging evidence indicates that extracellular vesicles, small vesicles secreted by most cell types and body fluids, are involved in cell-to-cell communication and are key players mediating biological processes such as inflammation, endothelial dysfunction or fibrosis, mechanisms present the onset and progression of hypertension-associated kidney disease. We address the potential use of extracellular vesicles as markers of hypertension-mediated kidney damage severity and their application as therapeutic agents in hypertension-associated renal damage. The capacity of exosomes to deliver a wide variety of cargos to the target cell efficiently makes them a potential drug delivery system for treatment of renal diseases.

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Novel biomarker and drug delivery systems for theranostics – extracellular vesicles

Bio-Algorithms and Med-Systems ◽

10.1515/bams-2021-0183 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Ewa Ł. Stępień ◽

Carina Rząca ◽

Paweł Moskal

Keyword(s):

Drug Delivery ◽

Extracellular Vesicles ◽

Drug Delivery Systems ◽

Biological Fluids ◽

Cell Types ◽

Biological Properties ◽

Delivery Systems ◽

Cell Uptake ◽

Positron Emission ◽

Composition Structure

Abstract Extracellular vesicles (EVs) are nano- and micro-sized double-layered membrane entities derived from most cell types and released into biological fluids. Biological properties (cell-uptake, biocompatibility), and chemical (composition, structure) or physical (size, density) characteristics make EVs a good candidate for drug delivery systems (DDS). Recent advances in the field of EVs (e.g., scaling-up production, purification) and developments of new imaging methods (total-body positron emission tomography [PET]) revealed benefits of radiolabeled EVs in diagnostic and interventional medicine as a potential DDs in theranostics.

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Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles

International Journal of Molecular Sciences ◽

10.3390/ijms22010138 ◽

2020 ◽

Vol 22 (1) ◽

pp. 138

Author(s):

Asit Kumar ◽

Lina Zhou ◽

Kaining Zhi ◽

Babatunde Raji ◽

Shelby Pernell ◽

...

Keyword(s):

Drug Delivery ◽

Neurodegenerative Diseases ◽

Drug Delivery System ◽

Extracellular Vesicles ◽

Delivery System ◽

Targeted Delivery ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Therapeutic Interventions ◽

Invasive Approach

Biomaterials have been the subject of numerous studies to pursue potential therapeutic interventions for a wide variety of disorders and diseases. The physical and chemical properties of various materials have been explored to develop natural, synthetic, or semi-synthetic materials with distinct advantages for use as drug delivery systems for the central nervous system (CNS) and non-CNS diseases. In this review, an overview of popular biomaterials as drug delivery systems for neurogenerative diseases is provided, balancing the potential and challenges associated with the CNS drug delivery. As an effective drug delivery system, desired properties of biomaterials are discussed, addressing the persistent challenges such as targeted drug delivery, stimuli responsiveness, and controlled drug release in vivo. Finally, we discuss the prospects and limitations of incorporating extracellular vesicles (EVs) as a drug delivery system and their use for biocompatible, stable, and targeted delivery with limited immunogenicity, as well as their ability to be delivered via a non-invasive approach for the treatment of neurodegenerative diseases.

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Monitoring Therapy Efficiency in Cancer through Extracellular Vesicles

Cells ◽

10.3390/cells9010130 ◽

2020 ◽

Vol 9 (1) ◽

pp. 130 ◽

Cited By ~ 1

Author(s):

Ines Stevic ◽

Gustav Buescher ◽

Franz Lennard Ricklefs

Keyword(s):

Early Diagnosis ◽

Extracellular Vesicles ◽

Cancer Progression ◽

Cell Communication ◽

Cell Types ◽

Phospholipid Bilayer ◽

Cancer Therapies ◽

Early Diagnosis Of Cancer ◽

Monitoring Therapy ◽

Diagnosis Of Cancer

Extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed vesicles made of a phospholipid bilayer and are secreted by all cell types. EVs are present in a variety of body fluids containing proteins, DNA, RNA species, and lipids, and play an important role in cell- to-cell communication and are worth being considered as biomarkers for both early diagnosis of cancer patients and real-time monitoring of treatment response. Recently, emerging evidence verified EVs to have crucial roles in cancer progression and metastasis and a great potential in therapeutic applications. In this review, we discuss the potential of EVs in monitoring the efficacy of cancer therapies.

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An Overview of Second Generation Nanoparticles− Nanostructure Lipid Carrier Drug Delivery System

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2020.13.6.2 ◽

2020 ◽

Vol 13 (6) ◽

pp. 5181-5189

Author(s):

Prabhat Kumar Sahoo ◽

Neha S.L ◽

Arzoo Pannu

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Second Generation ◽

Drug Loading ◽

Scale Up ◽

Delivery Systems ◽

Route Of Administration ◽

Random Structure ◽

Stability Parameters

Lipids are used as vehicles for the preparation of various formulations prescribed for administrations, including emulsions, ointments, suspension, tablets, and suppositories. The first parental nano-emulsion was discovered from the 1950s when it was added to the intravenous administration of lipid and lipid-soluble substances. Lipid-based drug delivery systems are important nowadays. Solid nanoparticles (SLN) and Nanostructured lipid carriers (NLC) are very proficient due to the ease of production process, scale-up capability, bio-compatibility, the biodegradability of formulation components and other specific features of the proposed route. The administration or nature of the materials must be loaded into these delivery systems. The main objectives of this review are to discuss an overview of second-generation nanoparticles, their limitations, structures, and route of administration, with emphasis on the effectiveness of such formulations. NLC is the second generation of lipid nanoparticles having a structure like nanoemulsion. The first generation of nanoparticles was SLN. The difference between both of them is at its core. Both of them are a colloidal carrier in submicron size in the range of 40-1000 nm. NLC is the most promising novel drug delivery system over the SLN due to solving the problem of drug loading and drug crystallinity. Solid and liquid lipids combination in NLC formation, improve its quality as compare to SLN. NLC has three types of structures: random, amorphous, and multiple. The random structure containing solid-liquid lipids and consisting crystal and the liquid lipid irregular in shape; thereby enhance the ability of the lipid layer to pass through the membrane. The second is the amorphous structure. It is less crystalline in nature and can prevent the leakage of the loaded drug. The third type is multiple structures, which have higher liquid lipid concentrations than other types. The excipients used to form the NLC are bio-compatible, biodegradable and non-irritating, most of which can be detected using GRAS. NLC is a promising delivery system to deliver the drug through pulmonary, ocular, CNS, and oral route of administration. Various methods of preparation and composition of NLC influence its stability Parameters. In recent years at the educational level, the potential of NLC as a delivery mechanism targeting various organs has been investigated in detail.

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Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

International Journal of Molecular Sciences ◽

10.3390/ijms21249585 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9585

Author(s):

Melania Dovizio ◽

Patrizia Ballerini ◽

Rosa Fullone ◽

Stefania Tacconelli ◽

Annalisa Contursi ◽

...

Keyword(s):

Drug Delivery ◽

Cancer Cells ◽

Immune Cells ◽

Expression Patterns ◽

Cell Communication ◽

Antiplatelet Agents ◽

Cell Types ◽

Disease Monitoring ◽

Crucial Component ◽

Numerous Cell

Platelets contribute to several types of cancer through plenty of mechanisms. Upon activation, platelets release many molecules, including growth and angiogenic factors, lipids, and extracellular vesicles, and activate numerous cell types, including vascular and immune cells, fibroblasts, and cancer cells. Hence, platelets are a crucial component of cell–cell communication. In particular, their interaction with cancer cells can enhance their malignancy and facilitate the invasion and colonization of distant organs. These findings suggest the use of antiplatelet agents to restrain cancer development and progression. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer-patient platelets show specific proteomic and transcriptomic expression patterns, a phenomenon called tumor-educated platelets (TEP). The transcriptomic/proteomic profile of platelets can provide information for the early detection of cancer and disease monitoring. Platelet ability to interact with tumor cells and transfer their molecular cargo has been exploited to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity often associated with traditional chemotherapy. Platelets are extraordinary cells with many functions whose exploitation will improve cancer diagnosis and treatment.

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A Review on Formulation and Development of Solid Self-Nano Emulsifying Drug Delivery Systems

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2021.14.4.1 ◽

2021 ◽

Vol 14 (4) ◽

pp. 5519-5228

Author(s):

Sunitha M Reddy ◽

Sravani Baskarla

Keyword(s):

Drug Delivery ◽

Dissolution Rate ◽

Drug Delivery System ◽

Delivery System ◽

Drug Delivery Systems ◽

Water Solubility ◽

Drug Loading ◽

Aqueous Solubility ◽

Delivery Systems ◽

Particle Size Reduction

This article describes current strategies to enhance aqueous solubility and dissolution rate of poor soluble drugs. Most drugs in the market are lipophilic with low or poor water solubility. There are various methods to enhance solubility: co-solvency, particle size reduction, salt formation and Self Nanoemulsifying drug delivery systems, SEDDS is a novel approach to enhance solubility, dissolution rate and bioavailability of drugs. The study involves formulation and evaluation of solid self-Nano emulsifying drug delivery system (S-SNEDDS) to enhance aqueous solubility and dissolution rate. Oral route is the most convenient route for non-invasive administration. S-SNEDDS has more advantages when compared to the liquid self-emulsifying drug delivery system. Excipients were selected depends upon the drug compatibility oils, surfactants and co surfactants were selected to formulate Liquid SNEDDS these formulated liquid self-nano emulsifying drug delivery system converted into solid by the help of porous carriers, Melted binder or with the help of drying process. Conversion process of liquid to solid involves various techniques; they are spray drying; freeze drying and fluid bed coating technique; extrusion, melting granulation technique. Liquid SNEDDS has a high ability to improve dissolution and solubility of drugs but it also has disadvantages like incompatibility, decreased drug loading, shorter shelf life, ease of manufacturing and ability to deliver peptides that are prone to enzymatic hydrolysis.

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MICROSPONGES AS A NEOTERIC CORNUCOPIA FOR DRUG DELIVERY SYSTEMS

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2019v11i3.34099 ◽

2019 ◽

pp. 4-12

Author(s):

SARIPILLI RAJESWARI ◽

VANAPALLI SWAPNA

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Drug Delivery Systems ◽

Active Agent ◽

Delivery Systems ◽

Oral Dosage ◽

Spherical Particles ◽

Porous Microspheres ◽

Oral Dosage Forms

Microsponges (MSPs) are at the forefront of the rapidly developing field of novel drug delivery systems which are gaining popularity due to their use for controlled release and targeted drug delivery. The microsponge delivery system (MDS) is a patented polymeric system consisting of porous microspheres typically 10-25 microns in diameter, loaded with an active agent. They are tiny sponge-like spherical particles that consist of a myriad of interconnecting voids within a non-collapsible structure with a large porous surface through which active ingredient is released in a controlled manner. Microsponge also hold a certification as one of the potential approaches for gastric retention where many oral dosage forms face several physiological restrictions due to non-uniform absorption pattern, inadequate medication release and shorter residence time in the stomach. This type of drug delivery system which is non-irritating, non-allergic, non-toxic, can suspend or entrap a wide variety of substances, and can then be incorporated into a formulated product such as gel, cream, liquid or powder that is why it is called as a “versatile drug delivery system”. It overcomes the drawbacks of other formulations such as frequency of dosing, drug reaction, incompatibility with environmental condition. These porous microspheres were exclusively designed for chronotherapeutic topical drug delivery but attempt to utilize them for oral, pulmonary and parenteral drug delivery were also made. The present review elaborates about the multifunctional microsponge technology including its preparation, characterization, evaluation methods along with recent research and future potential.

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Environment Responsive Metal–Organic Frameworks as Drug Delivery System for Tumor Therapy

Nanoscale Research Letters ◽

10.1186/s11671-021-03597-w ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Chao Yan ◽

Yue Jin ◽

Chuanxiang Zhao

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Drug Delivery Systems ◽

Tumor Therapy ◽

Metal Organic Frameworks ◽

Delivery Systems ◽

Drug Uptake ◽

High Concentration ◽

Metal Organic

AbstractNanoparticles as drug delivery systems can alter the drugs' hydrophilicity to affect drug uptake and efflux in tissues. They prevent drugs from non-specifically binding with bio-macromolecules and enhance drug accumulation at the lesion sites, improving therapy effects and reducing unnecessary side effects. Metal–organic frameworks (MOFs), the typical nanoparticles, a class of crystalline porous materials via self-assembled organic linkers and metal ions, exhibit excellent biodegradability, pore shape and sizes, and finely tunable chemical composition. MOFs have a rigid molecular structure, and tunable pore size can improve the encapsulation drug's stability under harsh conditions. Besides, the surface of MOFs can be modified with small-molecule ligands and biomolecule, and binding with the biomarkers which is overexpressed on the surface of cancer cells. MOFs formulations for therapeutic have been developed to effectively respond to the unique tumor microenvironment (TEM), such as high H2O2 levels, hypoxia, and high concentration glutathione (GSH). Thus, MOFs as a drug delivery system should avoid drugs leaking during blood circulation and releasing at the lesion sites via a controlling manner. In this article, we will summary environment responsive MOFs as drug delivery systems for tumor therapy under different stimuli.

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Extracellular Vesicles: An Emerging Nanoplatform for Cancer Therapy

Frontiers in Oncology ◽

10.3389/fonc.2020.606906 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yifan Ma ◽

Shiyan Dong ◽

Xuefeng Li ◽

Betty Y. S. Kim ◽

Zhaogang Yang ◽

...

Keyword(s):

Cancer Therapy ◽

Extracellular Vesicles ◽

Drug Delivery Systems ◽

Current Knowledge ◽

Drug Loading ◽

Cell Communication ◽

Cancer Therapies ◽

Therapeutic Function ◽

Cancer Studies ◽

Potential Use

Extracellular vesicles (EVs) are cell-derived membrane particles that represent an endogenous mechanism for cell-to-cell communication. Since discovering that EVs have multiple advantages over currently available delivery platforms, such as their ability to overcome natural barriers, intrinsic cell targeting properties, and circulation stability, the potential use of EVs as therapeutic nanoplatforms for cancer studies has attracted considerable interest. To fully elucidate EVs’ therapeutic function for treating cancer, all current knowledge about cellular uptake and trafficking of EVs will be initially reviewed. In order to further improve EVs as anticancer therapeutics, engineering strategies for cancer therapy have been widely explored in the last decade, along with other cancer therapies. However, therapeutic applications of EVs as drug delivery systems have been limited because of immunological concerns, lack of methods to scale EV production, and efficient drug loading. We will review and discuss recent progress and remaining challenges in developing EVs as a delivery nanoplatform for cancer therapy.

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