Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins.

By G. Fuhrmann, Andrea Serio, Manuel M Mazo, R. Nair, Molly M. Stevens. Journal of Controlled Release, 2015

663 citations recorded by the source corpus.

Extracellular vesicles (EVs) are phospholipid-based particles endogenously produced by cells. Their natural composition and selective cell interactions make them promising drug carriers. However, in order to harness their properties, efficient exogenous drug encapsulation methods need to be investigated. Here, EVs from various cellular origins (endothelial, cancer and stem cells) were produced and characterised for size and composition. Porphyrins of different hydrophobicities were employed as model drugs and encapsulated into EVs using various passive and active methods (electroporation, saponin, extrusion and dialysis). Hydrophobic compounds loaded very efficiently into EVs and at significantly higher amounts than into standard liposomes composed of phosphocholine and cholesterol using passive incubation. Moreover, loading into EVs significantly increased the cellular uptake by >60% and the photodynamic effect of hydrophobic porphyrins in vitro compared to free or liposome encapsulated drug. The active encapsulation techniques, with the saponin-assisted method in particular, allowed an up to 11 fold higher drug loading of hydrophilic porphyrins compared to passive methods. EVs loaded with hydrophilic porphyrins induced a stronger phototoxic effect than free drug in a cancer cell model. Our findings create a firm basis for the development of EVs as smart drug carriers based on straightforward and transferable methods.

Subfields: Biomedical Engineering, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/40f4ec44302f8af7192ce1173513eef8a216323e

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Citations in the corpus

Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications (2020, neutral): “The drug loading rate of exosomes may be related to the hydrophobicity of drugs, the drug loading method, the lipid composition of exosomes, etc. 100 .”
Bovine milk-derived exosomes for drug delivery (2015, background): “Recent studies have exploited the idea of both passive methods such as incubation [48] and active encapsulation techniques such as electroporation, saponin treatment, extrusion and hypotonic dialysis [49, 50] for drug loading in cell-derived exosomes.”
Naturally Occurring Exosome Vesicles as Potential Delivery Vehicle for Bioactive Compounds (2019, background): “This method of cargo loading was reported to increase the loading capacity of extracellular vesicles by up to 11 times when compared to passive cargo loading (Fuhrmann et al., 2015).”
Plant exosome like nanovesicles: Emerging therapeutics and drug delivery nanoplatforms. (2020, methodology): “It also has been published that this method takes precedence by boosting the cargo loading capability up to 11-fold over passive cargo loading.(56) In most conditions, PELNVs retain a negatively charged surface that can attract oppositely charged drugs such as doxorubicin and ultimately support the ”
Lipids in exosomes: Current knowledge and the way forward. (2017, background): “How can it be possible to document the product, including the reproducibility of different batches, as needed to obtain market approval for drugs? Although regulatory issues of exosome-based drug delivery have been mentioned in some reviews [9,89,91], there is not much focus on this challenge in the”