Objective: To evaluate the drug encasement in human dental pulp stem cell derived exosomes and its delivery in vitro in single cell level using fluorescence imaging and in vivo biodistribution using NIR imaging in a chronic PD rat model through intranasal route.
Background: Although, Parkinson’s disease is the 2nd most prevalent neurodegenerative disorder, much of the therapy available is not robust enough to reverse/slow down the disease pathology. This is partly due to the inability of the drugs to cross the BBB and First Pass metabolism. Oral-ingestion of these factors limits their availability in midbrain due to the blood brain barrier (BBB), and intrastriatal-delivery is impractical due to its invasive-nature. Exosomes, packed with necessary neurotrophic-factors secreted by their parent-cells, can also be ideal delivery-vehicles for antioxidants through intranasal-route.
Method: DPSC-Exosomes were isolated from Dental Pulp Stem Cells using density-gradient ultracentrifugation; characterized using Dynamic Light scattering, FACS and Transmission-Electron-Microscopy. Phloroglucinol(drug) incorporation into exosomes was performed through sonication and glycol content estimated in the exosomes encased phloroglucinol using ELISA. Uptake of exosomes was using real-time fluorescence microscopy in in-vitro dopaminergic-cells. Exo-phloroglucinol was labelled with NIR-dye and administered in control & MPTP-PD model and small-animal in-vivo NIR-imaging was performed to study biodistribution.
Results: The purity of exosomes isolated through ultracentrifugation was assessed using Dynamic Light Scattering with respect to size and more than 92% of exosomes were within the radii 90-100nm. TEM was used for exosome visualization and here too a similar size diameter was obtained. FACS analysis showed that the exosomes isolated from DPSCs were immunopositive for CD63, CD81 and CD9. Glycol content was measured for exosomal encasement of phloroglucinol and it significantly decreased the ROS levels in SH-SY5Y cells under 6-OHDA stress.
Conclusion: This work demonstrates the potential of DPSCs derived exosomes for ameliorating PD symptoms & demonstrate whether these exosomes can act as potent carriers for the therapeutic flavonoid phloroglucinol & can be delivered through intranasal route to reach the midbrain.
To cite this abstract in AMA style:I. Datta, A. Kaushal, K. Mondal. Exosomes from human dental pulp stem cells as a cell-free drug delivery vehicle in vitro and in vivo chronic PD rat model through the intranasal route targeting efficacy & bio-distribution. [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/exosomes-from-human-dental-pulp-stem-cells-as-a-cell-free-drug-delivery-vehicle-in-vitro-and-in-vivo-chronic-pd-rat-model-through-the-intranasal-route-targeting-efficacy-bio-distribution/. Accessed March 2, 2024.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/exosomes-from-human-dental-pulp-stem-cells-as-a-cell-free-drug-delivery-vehicle-in-vitro-and-in-vivo-chronic-pd-rat-model-through-the-intranasal-route-targeting-efficacy-bio-distribution/