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Engineered versus hybrid cellular vesicles as efficient drug delivery systems: a comparative study with brain
Maria Kannavou1,2, Antonia Marazioti1,2, Georgios T Stathopoulos3,4
1Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, 26510, Rio, Greece.
Drug Delivery and Translational Research
|January 20, 2021
Summary
Engineered cellular vesicles (e-CVs) and hybrid vesicles were developed as drug carriers. PEGylated e-CVs showed superior integrity and brain targeting potential compared to hybrids, making them promising for drug delivery.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery
Background:
- Cellular vesicles (CVs) are explored as drug carriers.
- Enhancing CVs with cholesterol (Chol) and PEG lipids improves their drug delivery capabilities.
- Hybrid vesicles formed by PEGylated liposomes (PEG-LIP) and CVs are investigated as an alternative to engineered CVs (e-CVs).
Purpose of the Study:
- To optimize methods for loading CVs and incorporating cholesterol and PEG lipids into their membranes.
- To evaluate engineered CVs (e-CVs) and hybrid vesicles for drug delivery applications.
- To compare the efficacy of e-CVs and hybrids as brain-targeted drug carriers.
Main Methods:
- Dehydration rehydration vesicle (DRV) method was used for CV loading.
- Freeze-thawing (FT) cycles and incubation protocols were tested for hybrid formation.
- Vesicle fusion monitored by FRET dilution; cell uptake studied using confocal microscopy; in vivo and ex vivo models used for brain accumulation assessment.
Main Results:
- DRV method yielded optimal CV loading and integrity.
- FT was more efficient than incubation for hybrid formation.
- PEGylated e-CVs exhibited higher integrity than hybrids and demonstrated better brain targeting, despite lower cellular uptake due to PEG content.
Conclusions:
- PEGylated e-CVs are superior to hybrids as brain-targeted drug carriers.
- Surface PEGylation is crucial for enhancing vesicle integrity and brain accumulation.
- Cellular uptake mechanisms differ between e-CVs (clathrin-dependent) and CVs/hybrids (caveolin-dependent).
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