Membrane fusion is considered relevant in countless scientific areas and biotechnological processes, ranging from vital life events to biomedicine, pharmaceuticals, and materials engineering, among others. In this study, we employed hydrophobic oleic acid (OA)-coated magnetite (Fe3O4) nanoparticles (MNP-OA) as a platform to induce the fusion of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine liposomes [large unilamellar vesicles (LUVs)] in a colloidal dispersion. This fusion was monitored through dynamic light scattering, turbidimetry, and fluorescence assay using the well-known Tb/dipicolinic acid (DPA) complex formation assay. MNP-OA have shown to be able to induce fusion with the mixing of liposomal inner content with direct dependence on the nanoparticle concentration added to the LUVs. Moreover, changes in the permeability of the liposome bilayer, upon the addition of MNP-OA to liposomes, were evaluated by studying the leakage of carboxyfluorescein and of the co-encapsulated Tb/DPA complex. These assays allowed us to determine that MNP-OA did not significantly modify liposome permeability during the fusion process. Transmission electron microscopy and confocal microscopy revealed that MNP-OA remained embedded in the lipid bilayer without producing membrane rupture, liposome deformation, or destruction. In addition, we evaluated the effect of applying a low-intensity magnetic field to the LUVs/MNP-OA system and observed that the nanoparticles considerably increased their fusogenic activity under this external stimulus, as well as they are capable of responding to low magnetic fields of around 0.45 mT. These results revealed the potential of hydrophobic magnetic nanoparticles, stabilized with OA, to act as a fusogen, thus representing a valuable tool for biotechnological applications.

l-ascorbic acid alkyl esters (ASCn) are lipophilic forms of vitamin C, which maintain some of its antioxidant power. Those properties make this drug family attractive to be used in pharmacological preparations protecting other redox-sensible drugs or designed to reduce possible toxic oxidative processes. In this work, we tested the ability of l-ascorbic acid alkyl esters (ASCn) to modulate the structure, permeability, and rheological properties of phospholipid bilayers. The ASCn studied here (ASC16, ASC14, and ASC12) alter the structural integrity as well as the rheological properties of phospholipid membranes without showing any evident detergent activity. ASC14 appeared as the most efficient drug in destabilize the membrane structure of nano- and micro-size phospholipid liposomes inducing vesicle content leakage and shape elongation on giant unilamellar vesicles. It also was the most potent enhancer of membrane microviscosity and surface water structuring. Only ASC16 induced the formation of drug-enriched condensed domains after its incorporation into the lipid bilayer, while ASC12 appeared as the less membrane-disturbing compound, likely because of its poor, and more superficial, partition into the membrane. We also found that incorporation of ASCn into the lipid bilayers enhanced the reduction of membrane components, compared with soluble vitamin C. Our study shows that ASCn compounds, which vary in the length of the acyl chain, show different effects on phospholipid vesicles used as biomembrane models. Those variances may account for subtly differences in the effectiveness on their pharmacological applications.