Harnessing exosomes and plant-derived exosomes as nanocarriers for the efficient delivery of plant bioactives

Abstract

Exosomes, a category of extracellular vesicle (EV), are phospholipid bilayer structures ranging from 30 to 150 nm, produced by various organisms through the endosomal pathway. Recent studies have established the utilization of exosomes as nanocarriers for drug distribution across various therapeutic areas including cancer, acute liver injury, neuroprotection, oxidative stress, inflammation, etc. The importance of plant-derived exosomes and exosome vesicles derived from mammalian cells or milk, loaded with potent plant bioactives for various therapeutic indications are discussed along with insights into future perspectives. Moreover, this review provides a detailed understanding of exosome biogenesis, their composition, classification, stability of different types of exosomes, and different routes of administration along with the standard techniques used for isolating, purifying, and characterizing exosomes.

Plain language summary

Exosomes are tiny, spherical structures made of two layers of lipids, measuring between 30 and 150 nm in diameter. They are flexible, less harmful to the immune system, can cross barriers in the body, and also can be used as vehicles to carry drugs. Various methods are used to obtain, separate, and purify the exosomes based on their size, shape, density, and specific markers. Exosomes obtained from plants can treat various diseases as they are less toxic, have high permeability, and are environmentally safe. The chemical compounds obtained from plants can be loaded into the exosomes obtained from sources like milk, or human cells both healthy and diseased, having the ability to treat cancer, inflammation, liver diseases, etc.

GRAPHICAL ABSTRACT

Article highlights

Introduction to exosomes

• Exosomes are small vesicles released by most eukaryotic cells, that facilitate intercellular communication and possess an extended half-life, allowing them to traverse extended distances within the body under both normal and disease conditions.

Advantages of exosomes

• The exceptional drug-delivery potential of exosomes, originating from their less immunogenic, non-cytotoxic, and non-mutagenic ability, surpasses that of liposomes.

• In advanced medicine, exosomes are investigated as a promising cell-free therapy due to their targeted effects on cells, reduced safety issues, and low manufacturing costs in comparison to cell-based therapies.

Challenges with exosomes

• Human cell-derived exosomes have scalability and scalability challenges associated with the low yield. To address this exosome-derived plants have emerged as a promising alternative.

Ethical concerns

• Researchers must thoroughly evaluate the potential risks associated with exosome-based therapies, including immunogenicity, off-target effects, and long-term complications. Patients should be fully informed about the nature of exosome therapy, including its potential benefits, risks, and uncertainties.

• In-depth investigation of the animal-derived, and plant-derived exosomes is required before using them for therapeutic interventions.

Advantages of plant-derived exosomes

• Plant-derived exosomes owing to their small size are considered to be environmentally safe, less toxic, and have high permeability; biological functions and pharmacological properties of plant-derived exosomes closely resemble those of their parent plants and often surpass those of isolated plant compounds.

Isolation & purification methods

• The selection of different isolation and purification methods such as ultracentrifugation, size-based separation, polymer-based methods, affinity-based separation, and microfluidic systems are to be taken care of as they can influence the purity and the physiological characteristics of the exosomes.

Future perspectives

• The plant-derived exosomes with their superior advantages of higher yield, widely available, prolonged half-life, and better stability in biological fluids show future potential for treatment strategy and therapeutic intervention.

Keywords: :

• animal-derived exosomes
• exosomes
• extracellular vesicles
• formulation
• nanomedicine
• plant-derived exosomes
• plant bioactives
• plant extract

Acknowledgments

The authors are extremely grateful to the Department of Pharmaceutical Engineering & Technology, IIT (BHU), Varanasi for providing infrastructural facilities.

Author contributions

P Kathait and PK Patel contributed to the conceptualization and writing of the original manuscript. AN Sahu contributed to conceptualization, supervision, expert assistance, editing, drafting and revision functions.

Financial disclosure

A N Sahu is thankful to the Council of Science and Technology, Uttar Pradesh (CST, UP) for providing funding (Sanction order no: CST/D-1163) for developing carbon nanodots for oral cancer. The financial assistance provided as a scholarship to P Kathait by the Ministry of Education (MoE), Government of India is greatly acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.