Adaptability and elasticity of the mixed lipid bilayer vesicles containing non-ionic surfactant designed for targeted drug delivery across the skin

Abstract

Novel potential carriers for non-invasive drug delivery were prepared from polyoxyethylene(20) oleyl ether (C_18:1EO₂₀) and soybean phosphatidylcholine (SPC) in different relative molar ratios, R_e; this produced stiff SPC liposomes (2r_ves∼120 nm) at one end and much smaller (2r_mic ≤ 15 nm), comparably non-deformable, mixed micelles at the other end of aggregate spectrum. Deformability of the mixed amphiphat vesicles (2r_v∼105 nm) existing in-between increases with R_e non-linearly, up to a quasi-plateau at R_e ≥ = 0.25 in the bilayer. The surfactant-saturated bilayers exhibit bending rigidity of κ_c∼2.1 k_BT, as determined with an improved vesicle adaptability assay involving analysis of normalised flux density through a nano-porous barrier as an activated transport process. Pore penetrability vs. driving pressure data measured with the mixed amphiphat vesicles resemble results of computer simulation of deformable vesicles penetrating a constriction [Gompper G, Kroll DM. 1995. Driven transport of fluid vesicles through narrow pores. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 52:4198-4208], confirming basic similarity of both processes. The improved assay can reveal partial lipid solubilisation at R_e>, which is linearly proportional to R_e − . C_18:1EO₂₀-SPC mixed vesicles that can cross narrow pores are arguably suitable for targeted drug delivery across intact skin.

Keywords: :

• Phosphatidylcholine
• polyoxyethylene(20) oleyl ether
• bilayer bending rigidity
• ultradeformable vesicle
• Transfersome®
• drug targeting
• transdermal drug delivery

Notes

^1. The latter binds to phosphatidylcholine, resulting in a complex with surfactant-like properties (Cevc 2004).

^3. The best amongst simple descriptors of the double-bond effect magnitude is the maximum number of double bonds per fatty chain in each lipid molecule, n_{C = C,max}—so long as n_{C = C,max} < 3—as this parameter in the first approximation determines bilayer thickness that affects bilayer rigidity with the second power.

^2. Some of the values reported earlier for EPC are higher: κ_c < 35 k_BT, with an average value of 21.9 k_BT, but there is a tendency towards lower values in the more recent papers (Petrov 1999).