Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles
Abstract
1. Introduction
2. Challenges and Implications of Biomaterials-Based Drug Delivery Approach in Neurodegenerative Diseases
3. Extracellular Vesicle-Based Drug Delivery Systems
3.1. EV Background
3.2. Drug Loading in EVs
3.2.1. Endogenous Drug Loading
3.2.2. Exogenous Drug Loading
3.3. EV-Based Drug Delivery for Neurodegenerative Diseases
3.3.1. AD
3.3.2. PD
3.3.3. MS
3.3.4. HAND
3.3.5. TBI
3.3.6. COVID-19 Associated Brain Damage
3.4. EV-Based Therapeutic Approach
4. Limitations of EV-Based Drug Delivery Systems and Current Advancements to Counter these Limitations
4.1. Interaction of Drugs with EV Components
4.2. In Vivo Pharmacokinetics of EV Drugs
4.2.1. Intravenous Injection (IV)
4.2.2. Intraperitoneal Injections, Subcutaneous Injections, and Oral Administration
4.3. Delivery of Drugs to the Target
4.4. Immune Clearance
5. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Material Classification | Name | Structure | References |
---|---|---|---|
Metal Elemental | Gold Nanoparticles (AuNPs) | Nanosphere | [12,13] |
Metal Elemental | Silver Nanoparticles (AgNPs) | Nanosphere | [14] |
Metal Oxide | Iron Oxide Nanoparticles | Nanosphere | [15,16] |
Metal Oxide | Cerium Oxide Nanoparticles | Nanosphere | [17,18] |
Metal Oxide | Zinc Oxide Nanoparticles | Nanosphere | [19,20] |
Inorganic Compound | Quantum Dots | Nano Tube | [21,22] |
Metalloid Elemental | Silica Nanoparticles (SiNPs) | Nanosphere | [23,24,25] |
Lipid | Liposomes | Nanosphere with Bilayer Surface | [26,27] |
Lipid | Micelles | Nanosphere | [28] |
Lipid | Solid Lipid Nanoparticles (SLN) | Nanosphere with Monolayer Surface | [29] |
Lipid | Extracellular Vesicles (EVs) | Nanosphere with Bilayer Surface | [30] |
Polymer | Polylactic Acid (PLA) | Porous Nanosphere | [31] |
Polymer | Poly Lactic-co-Glycolic Acid (PLGA) | Porous Nanosphere | [5,6] |
Polymer | Polyethylene Glycol (PEG) | Porous Nanosphere | [32] |
Polymer | Hydrogel | Porous Matrix | [10,11] |
Loaded Drug Type | Targeted Disease Cells | Drug Delivery Method | Clinical Trial Phase | Reference |
---|---|---|---|---|
miRNA (nucleic acid drug type) | EGFR-expressing breast cancer cells | Exosome surface modification w/GE11 peptides | unspecified | [150] |
Curcumin (anti-inflammatory) | Monocyte-derived myeloid cells associated with inflammation related autoimmune diseases | i.p. injection of exosomal curcumin into mice | unspecified | [158] |
Cas9 mRNA and antisense oligonucleotides | Leukemia cells and breast cancer cells | in vivo delivery of ASO-loaded EVs via i.p. injection in mice | unspecified | [160] |
siRNA molecules | Cells affected by AD (neurons, microglia, oligodendrocytes) | Mice administered i.v. injection of RVG-targeted exosomes | unspecified | [108] |
Catalase (antioxidant enzyme) | Cells of neurovascular unit affected by PD (neurons, astrocytes, and brain microvessel endothelial cells) | Intranasal administration of catalase-loaded exosomes | unspecified | [106] |
siRNA molecules | α-Syn aggregates of Lewy bodies associated with Parkinson’s Disease | Peripheral injection of siRNA modified exosomes in the brain of mice | unspecified | [161] |
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Kumar, A.; Zhou, L.; Zhi, K.; Raji, B.; Pernell, S.; Tadrous, E.; Kodidela, S.; Nookala, A.; Kochat, H.; Kumar, S. Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles. Int. J. Mol. Sci. 2021, 22, 138. https://doi.org/10.3390/ijms22010138
Kumar A, Zhou L, Zhi K, Raji B, Pernell S, Tadrous E, Kodidela S, Nookala A, Kochat H, Kumar S. Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles. International Journal of Molecular Sciences. 2021; 22(1):138. https://doi.org/10.3390/ijms22010138
Chicago/Turabian StyleKumar, Asit, Lina Zhou, Kaining Zhi, Babatunde Raji, Shelby Pernell, Erene Tadrous, Sunitha Kodidela, Anantha Nookala, Harry Kochat, and Santosh Kumar. 2021. "Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles" International Journal of Molecular Sciences 22, no. 1: 138. https://doi.org/10.3390/ijms22010138
APA StyleKumar, A., Zhou, L., Zhi, K., Raji, B., Pernell, S., Tadrous, E., Kodidela, S., Nookala, A., Kochat, H., & Kumar, S. (2021). Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles. International Journal of Molecular Sciences, 22(1), 138. https://doi.org/10.3390/ijms22010138