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Expert Opin Drug Deliv. 2016 Nov;13(11):1503-1512. Epub 2016 Aug 4.

Cell-penetrating self-nanoemulsifying drug delivery systems (SNEDDS) for oral gene delivery.

Author information

1
a Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy , University of Innsbruck , Innsbruck , Austria.
2
b Daniel Swarovski Research Laboratory, Department of Visceral, Transplant and Thoracic Surgery , Medical University Innsbruck , Innsbruck , Austria.
3
c Department for General, Visceral and Transplantation Surgery , Campus Virchow-Klinikum, Charité Universitätsmedizin , Berlin , Germany.
4
d Department of Anesthesiology and Critical Care Medicine , Medical University Innsbruck , Innsbruck , Austria.
5
e Institute of Analytical Chemistry and Radiochemistry , University of Innsbruck , Innsbruck , Austria.

Abstract

OBJECTIVE:

The aim of study was to investigate whether cell-penetrating peptides could amplify cellular uptake of plasmid DNA (pDNA) loaded self-nanoemulsifying drug delivery systems (SNEDDS) by mucosal epithelial cells, thereby enhancing transfection efficiency.

METHODS:

HIV-1 Tat peptide-oleoyl conjugate (TAT-OL) was synthesized through amide bond formation between HIV-1 Tat-protein 49-57 (TAT) and oleoyl-chloride (OL). SNEDDS formulation contained 29.7% each of Cremophor EL, Capmul MCM and Crodamol, 9.9% propylene glycol and 1% TAT-OL. SNEDDS with OL instead of TAT-OL served as control.

RESULTS:

Fluorescent-microscopy demonstrated 0.5% (m/v) nanoemulsions were suitable for subsequent studies. Mucus diffusion of nanoemulsion loaded with fluorescein diacetate (FDA) was 1.5-fold increased by incorporation of TAT-OL. Confocal microscopy confirmed that droplets of nanoemulsions were successfully internalized. Furthermore, quantitative analysis showed that addition of TAT-OL increases uptake of nanoemulsions by 2.3- and 2.6-folds after 2 and 4 hours of incubation, respectively. Cellular internalization pathways were found with substantial decrease in uptake in presence of indomethacin and chlorpromazine. Transfection efficiency investigated on HEK-293-cells was found to be 1.7- and 1.8-fold higher for SNEDDS loaded with TAT-OL compared to Lipofectin and control, respectively.

CONCLUSION:

In comparison to prevailing lipid and polymer-based delivery systems, these novel cell-penetrating SNEDDS likely represent most effective, simplistic and expedite dosage form for mucosal gene delivery.

KEYWORDS:

Cell-penetrating peptide; HIV-1 Tat protein; SNEDDS; cellular internalization; transfection efficiency

PMID:
27458781
DOI:
10.1080/17425247.2016.1213236
[Indexed for MEDLINE]

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