Surface Properties of Lipoplexes Modified with Mannosylerythritol Lipid-A and Tween 80 and Their Cellular Association

Abstract

For effective gene transfection into mammalian cells, numerous cationic lipids have been synthesized and formulated into cationic liposomes. [1][2][3] In general, the diverse cationic lipids contain a hydrophobic region, a linker and a cationic headgroup, which are substantially quite variable in different cationic lipids. However, in the cationic headgroup, the basic element is amine, which is responsible for DNA complexation as a protonized form. All four amine types, from primary to quaternary amine, have been reported in diverse cationic lipids and exhibited substantially different cellular association and gene transfection capabilities. 4,5) Understanding the key step in gene transfection, i.e. cellular association of lipoplexes, which is largely determined by the physiochemical properties of cationic liposomes and their lipoplexes, will provide valuable information for designing more effective cationic lipids and optimizing the liposomal formulation. Particle size and zeta potentials of lipoplexes are often reported when discussing their cellular association [6][7][8] ; however, another physiochemical property, the surface hydration of lipoplexes, is always neglected. Although the hydration levels of lipoplexes containing different liposomal formulations have been well established, 9-11) their effect on the cellular association of lipoplexes is still lacking.We reported previously that cationic liposomes, composed of dioleoylphosphatidylethanolamine (DOPE) and N,Nmethyl hydroxyethyl aminopropane carbamoyl cholesterol (MHAPC) or cholesteryl-3b-carboxyamindoethylene-N-hydroxyethylamine (OH-Chol), demonstrated distinctive differences in their cellular association and gene transfection efficiencies in vitro.12) The major differences between MHAPC and OH-Chol are the amine types and linkers shown in Fig. 1, with MHAPC having a tertiary amine linked to the cholesteryl skeleton by a carbamate ester, and OH-Chol having a secondary amine with an amido linker. To understand the different cellular association of lipoplexes composed of different cationic lipids, the effect of amine types and linkers on the surface properties, e.g. zeta potentials and surface hydration levels, was examined. Furthermore, mannosylerythritol lipid-A (MEL-A) is a newly developed biosurfactant 13) and modification of OH-Chol-liposomes with MEL-A markedly increased the gene transfection efficiency of plasmid DNA.14,15) Recent findings found that MEL-A induced membrane fusion between the target cells and cationic liposomes 16,17) ; however, the physiochemical mechanism of the fusion ability of MEL-A has not been fully understood. As a

Non-ionic Surfactant Modified Cationic Liposomes Mediated Gene Transfection in Vitro and in the Mouse Lung

“…Although MEL-A and Tween 80 modified MHAPC-liposomes similarly exhibited strong interaction with DNA by circular dichroism. 25) MEL-A has adhesive ability to cells 14,15) and did not decrease the zeta potetial of MHAPC-lipoplexes as compared to Tween 80 (Table 1). These information suggested that MEL-A has higher mucoadhesion ability than Tween 80 modified formulation and could retain the lipoplexes on mucus layer …”

“…3B(c)). The decreased cellular association of lipoplexes by Tween 80 was probably caused by the steric barrier of polyoxyethylene, the decreased zeta potential (Table 1) and the wetting surface of lipoplexes, 25) which were supposed to be disadvantageous in the cellular association of lipoplexes. Fig.…”

Cosmetic-Derived Mannosylerythritol Lipid-B-Phospholipid Nanoliposome: An Acid-Stabilized Carrier for Efficient Gastromucosal Delivery of Amoxicillin for In Vivo Treatment of Helicobacter pylori

“…This advantage has instigated several in vitro studies to evaluate the stability and drug release profile of PC-MEL-A liposomes in acidic environments. Moreover, incorporation of MEL-A significantly increases the negative ζ potentials (from 50 to 75 mV to a negative value of −14.6 and −21.7 mV) and decreases the surface pH levels of the MEL-A-modified cholesteryl-3β-carboxyamindoethylene- N -hydroxyethylamine (OH-Chol) liposomes by affecting the protonation of the secondary amine in OH-Chol . The findings of a previous study indicated that the molecular interaction via hydrogen bonds between MEL-A and liposome components may contribute to the enhanced stability against gastric acid .…”

“…Moreover, incorporation of MEL-A significantly increases the negative ζ potentials (from 50 to 75 mV to a negative value of −14.6 and −21.7 mV) and decreases the surface pH levels of the MEL-A-modified cholesteryl-3β-carboxyamindoethylene- N -hydroxyethylamine (OH-Chol) liposomes by affecting the protonation of the secondary amine in OH-Chol. 18 The findings of a previous study indicated that the molecular interaction via hydrogen bonds between MEL-A and liposome components may contribute to the enhanced stability against gastric acid. 15 Based on these findings, we hypothesized that MELs can be incorporated into liposomes to form an acid-resistant carrier for delivering antibiotics and effective treatment of H. pylori infection in vivo.…”

Highlighting the Role of Polymer Length, Carbohydrate Size, and Nucleic Acid Type in Potency of Glycopolycation Agents for pDNA and siRNA Delivery

“…There are many different approaches currently being taken to the development of delivery vehicles for siRNA, including polymers, lipids, viruses, gold nanoparticles, carbon nanotubes, and other nanosystems. ,− In particular, polymer-based delivery vehicles offer tunable structures and versatile combinations of different functionalities that allow achievement of desirable properties, including particle size, surface charge (zeta potential), and targeting ligand incorporation . Cationic polymers can bind with anionic siRNA to form polyplexes via electrostatic interactions and hydrogen bonding, thereby neutralizing the siRNA negative charge and protecting it from degradation.…”