Methodologies to Isolate and Purify Clinical Grade Extracellular Vesicles for Medical Applications

The use of extracellular vesicles (EV) in nano drug delivery has been demonstrated in many previous studies. In this study, we discuss the sources of extracellular vesicles, including plant, salivary and urinary sources which are easily available but less sought after compared with blood and tissue. Extensive research in the past decade has established that the breadth of EV applications is wide. However, the efforts on standardizing the isolation and purification methods have not brought us to a point that can match the potential of extracellular vesicles for clinical use. The standardization can open doors for many researchers and clinicians alike to experiment with the proposed clinical uses with lesser concerns regarding untraceable side effects. It can make it easier to identify the mechanism of therapeutic benefits and to track the mechanism of any unforeseen effects observed.

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Engineered Extracellular Vesicles: Tailored-Made Nanomaterials for Medical Applications

Nanomaterials ◽

10.3390/nano10091838 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1838

Author(s):

Kenny Man ◽

Mathieu Y. Brunet ◽

Marie-Christine Jones ◽

Sophie C. Cox

Keyword(s):

Extracellular Vesicles ◽

Tissue Regeneration ◽

State Of The Art ◽

Medical Applications ◽

Clinical Use ◽

Current State ◽

Pathological Conditions ◽

Potential Efficacy ◽

Biomimetic Nanoparticles ◽

Natural Cell

Extracellular vesicles (EVs) are emerging as promising nanoscale therapeutics due to their intrinsic role as mediators of intercellular communication, regulating tissue development and homeostasis. The low immunogenicity and natural cell-targeting capabilities of EVs has led to extensive research investigating their potential as novel acellular tools for tissue regeneration or for the diagnosis of pathological conditions. However, the clinical use of EVs has been hindered by issues with yield and heterogeneity. From the modification of parental cells and naturally-derived vesicles to the development of artificial biomimetic nanoparticles or the functionalisation of biomaterials, a multitude of techniques have been employed to augment EVs therapeutic efficacy. This review will explore various engineering strategies that could promote EVs scalability and therapeutic effectiveness beyond their native utility. Herein, we highlight the current state-of-the-art EV-engineering techniques with discussion of opportunities and obstacles for each. This is synthesised into a guide for selecting a suitable strategy to maximise the potential efficacy of EVs as nanoscale therapeutics.

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Hydrogel-By-Design: Smart Delivery System for Cancer Immunotherapy

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.723490 ◽

2021 ◽

Vol 9 ◽

Author(s):

Rongwei Cui ◽

Qiang Wu ◽

Jing Wang ◽

Xiaoming Zheng ◽

Rongying Ou ◽

...

Keyword(s):

Drug Delivery ◽

Cancer Immunotherapy ◽

Drug Delivery Systems ◽

Malignant Tumors ◽

Delivery Systems ◽

The Past ◽

Therapeutic Benefits ◽

Localized Drug Delivery ◽

Smart Drug ◽

Smart Drug Delivery

Immunotherapy has emerged as a promising strategy for cancer treatment, in which durable immune responses were generated in patients with malignant tumors. In the past decade, biomaterials have played vital roles as smart drug delivery systems for cancer immunotherapy to achieve both enhanced therapeutic benefits and reduced side effects. Hydrogels as one of the most biocompatible and versatile biomaterials have been widely applied in localized drug delivery systems due to their unique properties, such as loadable, implantable, injectable, degradable and stimulus responsible. Herein, we have briefly summarized the recent advances on hydrogel-by-design delivery systems including the design of hydrogels and their applications for delivering of immunomodulatory molecules (e.g., cytokine, adjuvant, checkpoint inhibitor, antigen), immune cells and environmental regulatory substances in cancer immunotherapy. We have also discussed the challenges and future perspectives of hydrogels in the development of cancer immunotherapy for precision medicine at the end.

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A Critical Review of Standardization of Ayurvedic Dosage Form Kwatha - Part - II: Approaches and Outcome

International Journal of Ayurvedic Medicine ◽

10.47552/ijam.v11i3.1552 ◽

2020 ◽

Vol 11 (3) ◽

pp. 378-386

Author(s):

Narendra Bhatt ◽

Manasi Deshpande ◽

Sunetra Chaskar

Keyword(s):

Drug Delivery ◽

Conventional Medicine ◽

Dosage Forms ◽

Raw Material ◽

New Techniques ◽

Preparation Methods ◽

Therapeutic Benefits ◽

Nano Drug Delivery ◽

Liquid Preparation ◽

Manufacturing Technologies

A Kwatha, decoction, is one of the most used classical Ayurvedic dosage forms. It is a liquid preparation to be freshly consumed. For this preparation the raw material, mostly herbs or a group of herbs are extracted in water by boiling them for a specific time span. This is second part of the review paper on Ayurvedic Kwatha - herbal decoction to review and consider various approaches and their outcomes for the standardization. It provides information and reference data for the standardization of decoction across conventional methods and new techniques and explains how this classical process has evolved within new pharmaceutical developments. Many Ayurvedic production units appear to have adapted to newer manufacturing technologies including fermentation techniques. This paper explores the scope for application of newer technologies for the purpose of better standardization and novel product applications. Application of Kwatha's nano-drug delivery systems have a promising potential to enhance operation and resolve issues related to classical dosage forms. In order to tackle further chronic diseases, the incorporation of nano-carriers as NDDS in the conventional medicine system is necessary. This review examines the benefits of the nano-drug delivery system, its properties, its drawbacks, forms of nanoparticles, their preparation methods, and various herbal nano medicines. This review further explores how therapeutic benefits can be improved by reducing toxicity and increasing bioavailability.

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Factors Affecting Extracellular Vesicles Based Drug Delivery Systems

Molecules ◽

10.3390/molecules26061544 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1544

Author(s):

Isha Gaurav ◽

Abhimanyu Thakur ◽

Ashok Iyaswamy ◽

Xuehan Wang ◽

Xiaoyu Chen ◽

...

Keyword(s):

Drug Delivery ◽

Extracellular Vesicles ◽

Targeted Delivery ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Factors Affecting ◽

Open Questions ◽

Nano Drug Delivery ◽

Different Origins

Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted delivery of therapeutic cargo, i.e., in drug delivery systems (DDS). This review summarizes recent studies pertaining to the development of EV-based DDS and its advantages compared to conventional nano drug delivery systems (NDDS). First, we compare liposomes and exosomes in terms of their distinct benefits in DDS. Second, we analyze what to consider for achieving better isolation, yield, and characterization of EVs for DDS. Third, we summarize different methods for the modification of surface of EVs, followed by discussion about different origins of EVs and their role in developing DDS. Next, several major methods for encapsulating therapeutic cargos in EVs have been summarized. Finally, we discuss key challenges and pose important open questions which warrant further investigation to develop more effective EV-based DDS.

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A simple, high-throughput method of protein and label removal from extracellular vesicle samples

10.1101/2020.08.20.260307 ◽

2020 ◽

Author(s):

Joshua A. Welsh ◽

Bryce Killingsworth ◽

Julia Kepley ◽

Tim Traynor ◽

Kathy McKinnon ◽

...

Keyword(s):

Extracellular Vesicles ◽

High Throughput ◽

Clinical Setting ◽

Clinical Utility ◽

Extracellular Vesicle ◽

Isolation And Purification ◽

Cell Processing ◽

Flow Cytometric ◽

High Throughput Method ◽

Purification Methods

AbstractEvidence continues to increase of the clinical utility extracellular vesicles (EVs) can provide as translational biomarkers. While a wide variety of EV isolation and purification methods have been implemented, few techniques are high-throughput and scalable for removing excess fluorescent reagents (e.g. dyes, antibodies). EVs are too small to be recovered from routine cell-processing procedures, such as filtration or centrifugation. The lack of suitable methods for removing unbound labels, especially in optical assays, is a major roadblock to accurate EV phenotyping and utilization of EV assays in a translational or clinical setting. Therefore, we developed a method for using a multi-modal resin, referred to as EV-Clean, to remove unbound labels from EV samples, and we demonstrate improvement in flow cytometric EV analysis with the use of this EV-Clean method.

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Optimised Electroporation for Loading of Extracellular Vesicles with Doxorubicin

Pharmaceutics ◽

10.3390/pharmaceutics14010038 ◽

2021 ◽

Vol 14 (1) ◽

pp. 38

Author(s):

Angus J. Lennaárd ◽

Doste R. Mamand ◽

Rim Jawad Wiklander ◽

Samir EL Andaloussi ◽

Oscar P. B. Wiklander

Keyword(s):

Drug Delivery ◽

Adverse Effects ◽

Field Strength ◽

Extracellular Vesicles ◽

The Body ◽

Clinical Use ◽

Chemotherapeutic Drug ◽

Small Molecule Drugs ◽

Drug Potency ◽

Delivery Platform

The clinical use of chemotherapeutics is limited by several factors, including low cellular uptake, short circulation time, and severe adverse effects. Extracellular vesicles (EVs) have been suggested as a drug delivery platform with the potential to overcome these limitations. EVs are cell-derived, lipid bilayer nanoparticles, important for intercellular communication. They can transport bioactive cargo throughout the body, surmount biological barriers, and target a variety of tissues. Several small molecule drugs have been successfully incorporated into the lumen of EVs, permitting efficient transport to tumour tissue, increasing therapeutic potency, and reducing adverse effects. However, the cargo loading is often inadequate and refined methods are a prerequisite for successful utilisation of the platform. By systematically evaluating the effect of altered loading parameters for electroporation, such as total number of EVs, drug to EV ratio, buffers, pulse capacitance, and field strength, we were able to distinguish tendencies and correlations. This allowed us to design an optimised electroporation protocol for loading EVs with the chemotherapeutic drug doxorubicin. The loading technique demonstrated improved cargo loading and EV recovery, as well as drug potency, with a 190-fold increased response compared to naked doxorubicin.

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Lipid-Based Nanovesicular Drug Delivery Systems

Nanomaterials ◽

10.3390/nano11123391 ◽

2021 ◽

Vol 11 (12) ◽

pp. 3391

Author(s):

Tania Limongi ◽

Francesca Susa ◽

Monica Marini ◽

Marco Allione ◽

Bruno Torre ◽

...

Keyword(s):

Drug Delivery ◽

Extracellular Vesicles ◽

Biochemical Composition ◽

Drug Delivery Systems ◽

Chemical Nature ◽

Nanometer Scale ◽

Pharmaceutical Chemical ◽

The Past ◽

Catanionic Vesicles ◽

The Many

In designing a new drug, considering the preferred route of administration, various requirements must be fulfilled. Active molecules pharmacokinetics should be reliable with a valuable drug profile as well as well-tolerated. Over the past 20 years, nanotechnologies have provided alternative and complementary solutions to those of an exclusively pharmaceutical chemical nature since scientists and clinicians invested in the optimization of materials and methods capable of regulating effective drug delivery at the nanometer scale. Among the many drug delivery carriers, lipid nano vesicular ones successfully support clinical candidates approaching such problems as insolubility, biodegradation, and difficulty in overcoming the skin and biological barriers such as the blood–brain one. In this review, the authors discussed the structure, the biochemical composition, and the drug delivery applications of lipid nanovesicular carriers, namely, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes, phytosomes, catanionic vesicles, and extracellular vesicles.

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Application of Nanotechnology in Biomedicine: A Major Focus on Cancer Therapy

Journal of Nano Research ◽

10.4028/www.scientific.net/jnanor.35.55 ◽

2015 ◽

Vol 35 ◽

pp. 55-66 ◽

Cited By ~ 7

Author(s):

Hadi Zare-Zardini ◽

Farzad Ferdowsian ◽

Hossein Soltaninejad ◽

Adel Ghorani Azam ◽

Safoura Soleymani ◽

...

Keyword(s):

Drug Delivery ◽

Controlled Release ◽

Cancer Detection ◽

Tumor Targeting ◽

Medical Applications ◽

Nano Materials ◽

Major Focus ◽

The Past ◽

New Compounds ◽

Cancer Diseases

Most of mortality worldwide occurs because of cancer diseases. Nanostructures are the new compounds that have become one of the most important technologies for using in different fields over the past two years especially in medicine. In between, nanotechnology has the potential to cancer detection and therapy. This study is a review of prospects in applications of nano-materials for cancer detection and treatment. We have summarized the nano-materials (metal nanospheres, nanorods, nanoshells and nanotubes) in medical applications targeting cancer. We also discuss advances in established nanoparticle technologies such as liposomes, polymer micelles, and functionalization about tumor targeting, controlled release and drug delivery. This paper will discuss the therapeutic applications of different nano-materials with a major focus on their applications for the treatment of cancer. Briefly, the toxicity of conventional nanostructures was also mentioned in this paper.

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