Phospholipid Vesicles for Dermal/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties

Abstract

This is a comprehensive review on the use of phospholipid nanovesicles for dermal/transdermal and nasal drug administration. Phospholipid-based vesicular carriers have been widely investigated for enhanced drug delivery via dermal/transdermal routes. Classic phospholipid vesicles, liposomes, do not penetrate the deep layers of the skin, but remain confined to the upper stratum corneum. The literature describes several approaches with the aim of altering the properties of these vesicles to improve their penetration properties. Transfersomes and ethosomes are the most investigated penetration-enhancing phospholipid nanovesicles, obtained by the incorporation of surfactant edge activators and high concentrations of ethanol, respectively. These two types of vesicles differ in terms of their structure, characteristics, mechanism of action and mode of application on the skin. Edge activators contribute to the deformability and elasticity of transfersomes, enabling them to penetrate through pores much smaller than their own size. The ethanol high concentration in ethosomes generates a soft vesicle by fluidizing the phospholipid bilayers, allowing the vesicle to penetrate deeper into the skin. Glycerosomes and transethosomes, phospholipid vesicles containing glycerol or a mixture of ethanol and edge activators, respectively, are also covered. This review discusses the effects of edge activators, ethanol and glycerol on the phospholipid vesicle, emphasizing the differences between a soft and an elastic nanovesicle, and presents their different preparation methods. To date, these differences have not been comparatively discussed. The review presents a large number of active molecules incorporated in these carriers and investigated in vitro, in vivo or in clinical human tests.

Short Onset and Enhanced Analgesia Following Nasal Administration of Non-Controlled Drugs in Nanovesicular Systems

“…These phospholipid nanovesicular systems contain soft vesicles due to the presence of propylene glycol, a lipid bilayers fluidizer [ 23 , 25 ]. The pH values for KET-NVS, BUT-NVS and TRA-NVS were 5.54 ± 0.06, 5.79 ± 0.03 and 5.0 ± 0.04, respectively.…”

“…The ability of the nasal nanovesicular carrier to enhance the delivery of analgesic drugs is attributed to the softness of the phospholipid vesicles. Such vesicles are, in general, formed in the presence of a bilayer fluidizing agent [ 25 ]. Ethosome was the first described phospholipid vesicle with bilayers fluidized by ethanol that was used for dermal delivery [ 32 , 33 ].…”

“…Our group has pioneered the design of nasal nanocarriers based on phospholipid soft vesicles for rapid and enhanced effect of active molecules [ 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. In a recent review, we have emphasized that phospholipid soft nanovesicles are generated in the presence of alcohols [ 25 ]. The first nasal carrier, containing nanovesicles with bilayers altered by ethanol, was introduced by Touitou et al [ 18 ].…”

Recent Progress in Transdermal Nanocarriers and Their Surface Modifications

“…Ethosomes and transfersomes are the most investigated innovative lipid-based nanovesicles, with increased softness, deformability, and elasticity [ 37 ]. Ethosomes, composed of phospholipid and ethanol, are generally formed as multilamellar nanovesicles.…”

Direct Potentiometric Study of Cationic and Nonionic Surfactants in Disinfectants and Personal Care Products by New Surfactant Sensor Based on 1,3-Dihexadecyl−1H-benzo[d]imidazol−3-ium

“…Nonionic surfactants enhance the cleaning properties of cationic surfactants [ 4 ]. Formulations of cationic with nonionic surfactants are common in personal care products and pharmaceuticals [ 5 , 6 ].…”