Exosomes are intracellular membrane-based vesicles with diverse compositions that are involved in biological and pathological processes. Since the discovery of exosomes, they have been used as diagnostic biomarkers and as potential drug delivery vehicles based on their size and competence to transfe...
Exosomes are intracellular membrane-based vesicles with diverse compositions that are involved in biological and pathological processes. Since the discovery of exosomes, they have been used as diagnostic biomarkers and as potential drug delivery vehicles based on their size and competence to transfer biological materials to recipient cells. The properties of exosomes such as biocompatibility, preferred tumor homing, adjustable targeting efficiency, and stability make them striking and excellent drug delivery vehicles for use in various diseases and cancer therapy. In this article, we provide a brief overview of the biogenesis, functions, and contents of exosomes along with the separation and characterization techniques. Our major focus is on the recent progress made in application of exosomes as drug delivery systems involving delivery of small molecules, macromolecules, and nucleotides. Further, we discuss the challenges faced when using exosomes as a drug delivery vehicle.
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Presented By Naveen Patidar M.Pharm (I.P.) 1 st sem 08011PY23MP08 EXOSOME DRUG DELIVERY SYSTEMS: REVOLUTIONIZING DRUG DELIVERY Guided By Mr. Prakash Soni Associate Professor Dept. of Pharmacy SGSITS Indore 1
CONTENT Introduction to exosome Biogenesis of exosome Structure of exosome Properties of exosomes Types of exosomes Isolation techniques Loading of drug Storage stability and limitation Summary Conclusion References 2
1 . INTRODUCTION Exosomes are extracellular membrane bound cell-secreted nanoparticles /vesicles size - 30–150 nm in diameter N atural nanocarriers derived from cell containing protein, lipid, RNA, DNA , Glycoprotein Cell to cell communication Used as cargo drug delivery 3
2. BIOGENESIS OF EXOSOMES MVB - MULTIVESICULAR BODIES ILV - INTRA LUMINAL VESSICLE ESCRT -ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT (MVB) 4
➤ Classification of extracellular vesicles according to the mechanism of generation . Exosomes are generated intracellularly from multivesicular bodies. Microvesicles( 100–1000 nm ) are produced by budding from the extracellular membrane. Apoptotic vesicles( 100–1000 nm) are released upon cell fragmentation during apoptotic cell death. FIG.SOURCE-; Pradip B. Devhare and Ratna B. Ray Mol Aspects Med. 2018 Apr; 60: PAGE 115 5
3. STRUCTURE E xosomes loaded with Proteins, e.g., heat shock proteins, Ras-related protein CD9, CD63, and CD81. mRNA, miRNA, and non-coding RNA Nutrients Bioactive compounds S tructural lipids include ceramide, sphingolipids, and phospholipid exosome membrane proteins include MHC-II, cluster of differentiation, and integrin. (source: ront . Sustain. Food Syst., Volume 3 – 2019) 6
4. PROPERTIES 7
DIAGNOSTICS ARTHRITIS PATHOLOGICAL CONDITIONS CANCER AS TARGETED DRUG DELIEVRY INTERCELLULAR COMMUNICATION BIOMARKER NEURODEGENRATIVE DISEASE IMMUNOTHERAPY BRAIN INFLAMMATORY DISEASE 8
6. ISOLATION TECHNIQUE A. ULTRACENTRIFUGATION B. DENSITY GRADIENT CENTRIFUGATION C. DEAD END FILTRATION D. TANGENTIAL FLOW FILTRATION E. SIZE-EXCLUSION CHROMATOGRAPHY F. IMMUNOAFFINITY image source Front. Bioeng. Biotechnol. 9:811971. doi: 10.3389/fbioe.2021.811971 CD9, CD63, CD81 10
7. LOADING OF EXOSOME Source;Exosome engineering in cell therapy and drug delivery. Inflammopharmaco l 31 , 145–169 (2023). 11
8. STORAGE STABLITY & LIMITATIONS They cannot be stored for a long time. It is necessary to study exosomes preservation technology to protect their biological activities and make them convenient for transportation and clinical application. Currently, the applied protection techniques mainly include Cryopreservation Freeze-drying (lyophilization) Spray-drying 12
9. SUMMARY Exosomes, natural carriers, offer targeted delivery potential for efficient and less toxic therapy. Diverse loading strategies establish exosomes as versatile carriers for various therapeutic molecules. Challenges include large-scale production, quality control, and potential side effects. Engineering exosomes with recognition proteins enhances targeted delivery and circulation time. Exosome source selection is crucial, considering different features and compositions. Concerns about tumor cell-derived exosomes inducing tumor growth must be addressed. 13
10. CONCLUSION Exosomes, with their hybrid systems, are considered alternative drug carriers for chemotherapy, gene therapy, and photothermal therapy. Hybrid exosomes show synergistic theragnosis effects but come with challenges like high synthesis cost. Mass production and improved drug loading efficiency are critical for commercialization and widespread therapeutic use. Exosomes and their hybrids offer advantages such as high targeting, non-toxicity, and biocompatibility. Overall, exosomes present promising potential in DDS for the treatment of various diseases, contributing to public health. 14
11. REFERENCES Chen H, Wang L, Zeng X, Schwarz H, Nanda HS, Peng X and Zhou Y (2021) Exosomes, a New Star for Targeted Delivery. Front. Cell Dev. Biol. 9:751079. doi: 10.3389/fcell.2021.751079 ACS Biomaterials Science & Engineering 2023 9 (2), 577-594 DOI:10.1021/ acsbiomaterials . Nature Nanotechnology | VOL 16 | July 2021 | 748–759 | www.nature.com/naturenanotechnology Heon Lee,a Kushal Chakraborty,b Joon Hwangac and Yong-Kyu Lee RSC Adv., 2022, 12, 18475–18492 | DOI: 10.1039/d2ra02351 15