Development and In Vitro Characterization of Transferrin-Decorated Nanoemulsion Utilizing Hydrophobic Ion Pairing for Targeted Cellular Uptake

Abstract

Purpose The aim of this study was to develop transferrin-conjugated nanoemulsions utilizing hydrophobic ion pairing for a targeted cellular uptake. Methods In the lipophilic phase of nanoemulsion composed of 60% oleic acid, 30% Capmul MCM EP and 10% Span 85, 1% cetyltrimethylammonium bromide (CTAB) and 3% phosphatidic acid (PA) were incorporated. After emulsification, the resulting droplets were decorated with human protein transferrin via hydrophobic ion pairing with PA and characterized regarding droplet size and zeta potential. Subsequently, cellular uptake of transferrin-conjugated nanoemulsion was investigated on Caco-2 and HeLa cell lines and determined by flow cytometry, cell lysis method and live cell imaging using confocal laser scanning microscopy. Results The nanoemulsion showed a droplet size of 123.03 ± 2.1 nm and zeta potential of − 54.5 mV that changed because of the surface decoration with transferrin to 182.7 ± 0.2 and + 30.2 mV, respectively. Within the uptake studies utilizing flow cytometry, transferrin-conjugated nanoemulsion showed a 5.2-fold higher uptake in Caco-2 cells and twofold improvement in case of HeLa cells compared with unmodified formulation. The outcome was confirmed visually via live cell imaging. Conclusion According to the results, transferrin-conjugated nanoemulsion might be considered as a promising drug delivery system for a selective receptor-mediated drug delivery.

Nanoemulsions: Formulation, characterization, biological fate, and potential role against COVID-19 and other viral outbreaks

“…Since passive targeting is based on the size of drug delivery systems, the specificity of passive targeting is limited, particularly when cancerous and normal cells cannot be effectively distinguished [ 159 ]. However, active targeting is another approach based on functionalized nanomaterials surfaces that display targeting moieties [ 11 , 160 ], attached through bioconjugation techniques. O/W NEs are also applied as stimuli-responsive platforms to overcome MDR and improve cancer therapeutics [ 161 ].…”

“…The potential of NEs for improving the quality and efficacy of pharmaceutical compounds has been demonstrated in various medical applications [ 9 ]. In particular, the large surface area-to-volume ratio of NEs enhances absorption and efficacy of encapsulated drugs, and the tunable interfacial properties of NEs enable targeted delivery of the loaded cargo to the intended site of action [ 10 , 11 ]. For example, NEs can be formulated with surface-displayed targeting biomolecules, such as antibodies, to facilitate targeted delivery.…”