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

• Published in: Expert opinion on drug delivery Vol. 13; no. 11; p. 1503
• Main Authors: Mahmood, Arshad, Prüfert, Felix, Efiana, Nuri Ari, Ashraf, Muhammad Imtiaz, Hermann, Martin, Hussain, Shah, Bernkop-Schnürch, Andreas
• Format: Journal Article
• Language: English
• Published: England 01.11.2016
• Subjects: Administration, Oral; Cell-Penetrating Peptides - metabolism; Chemistry, Pharmaceutical; Drug Delivery Systems; Emulsions; Genetic Therapy - methods; HEK293 Cells; Humans; Lipids; Transfection; cellular internalization; SNEDDS; HIV-1 Tat protein; transfection efficiency; Cell-penetrating peptide
• ISSN: 1744-7593
• DOI: 10.1080/17425247.2016.1213236

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. 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. 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. 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.