Cellular Uptake of Self-Emulsifying Drug-Delivery Systems: Polyethylene Glycol Versus Polyglycerol Surface

Abstract

Aim: Comparison of the impact of polyethylene glycol (PEG) and polyglycerol (PG) surface decoration on self-emulsifying drug delivery system (SEDDS)-membrane interaction and cellular uptake. Materials & methods: PEG-, PEG/PG- and PG-SEDDS were assessed regarding their self-emulsifying properties, surface charge, bile salt fusibility, cellular uptake and interaction with endosome-mimicking membranes. Results: SEDDS exhibited droplet sizes between 150 and 175 nm, a narrow size distribution and self-emulsified within 7 min. Higher PEG-surfactant amounts in SEDDS resulted in charge-shielding and thus in a decrease of ζ potential up to Δ11 mV. The inert PEG-surface hampered bile salt fusion and interfered SEDDS–cell interaction. By reducing the PEG-surfactant amount to 10%, cellular uptake increased twofold compared with PEG-SEDDS containing 40% PEG-surfactant. PG-SEDDS containing no PEG-surfactants showed a threefold increased cellular uptake. Furthermore, complete replacement of PEG-surfactants by PG-surfactants led to enhanced cellular interaction and improved disruption endosome-like membranes. Conclusion: PG-surfactants demonstrated high potential to address PEG-surface associated drawbacks in SEDDS.

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

“…In contrast to PEG, short-chain PG-surfactants with a polymerization degree (PD) below 10 prevented bile salt fusion and resulted in a greater decrease in zeta potential and size of the NC. [67] This observation matches findings on the polymerization degree (PD) necessary to provide protein resistance. PDs below 20 were sufficient to prevent the interaction with proteins, whereas for PG surfaces with a PD ≤ 10 protein-surface interactions could be detected.…”

“…Compared to SEDDS formulated with Tween 80 as common PEG‐surfactant, the PG‐surfactant provided less pronounced charge shielding, favoring the SEDDS–cell interaction. [ 67 ] Moreover, the partial replacement of long‐chain PEG‐surfactants or mixtures with short‐chain PG‐surfactants resulted in either equal but mostly improved internalization or cell penetrating properties of SEDDS. [ 74 ] On this basis, the cellular interaction of PG‐coated NC might be adjustable by MW, architecture and grafting density to enable bioinert properties without fully sacrificing the interactive properties of the NC surface with cells.…”

“…However, stealth coatings harm the interactive properties of NCs at their target site. They may prevent targeting ligands on the surface of NCs from binding to the target receptor, sterically hinder cellular uptake, [67] and interfere with the release of drugs from NCs. [166,167] This dilemma can be addressed by stealth coatings that are cleaved at the target site by specific stimuli including pH, enzymes, and local hypoxia.…”

Preparation and Evaluation of Charge Reversal Solid Lipid Nanoparticles

“…In addition, cytotoxicity of P-PEG-9-lauryl ether as well as PEG-9-lauryl ether was determined utilizing a slightly modified resazurin assay on a Caco-2 cell line [35]. In brief, Caco-2 cells were seeded on a 96-well plate in a density of 5 x 10 5 cells per well and incubated for 3 days in minimal essential media (MEM) supplemented with 10 % (v/v) heat-inactivated fetal calf serum and penicillin-streptomycin solution (100 units/0.1 mg/L).…”

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

“…Within this study, cellular uptake of Tf-conjugated NE was investigated on Caco-2 cells as well as on HeLa cells utilizing flow cytometry (Attune NxT Flow Cytometer) following a slightly adopted method described by Friedl et al [19]. In brief, formulation labelled with 0.15% (m/m) LGY was conjugated with Tf via HIP building up a protein corona as already described above.…”