Menthosomes, Novel Ultradeformable Vesicles for Transdermal Drug Delivery: Optimization and Characterization

Abstract

Menthosomes, novel deformable carriers for the enhancement of transdermal delivery are introduced in this study. Meloxicam (MX)-loaded menthosomes were formulated, and their physicochemical characteristics and skin permeability were evaluated. A two-factor spherical and second-order composite experimental design was used to prepare the formulation of the menthosomes. Ten formulations of menthosomes composed of a phospholipid as the lipid bilayer carrier, cholesterol (Chol) as a stabilizer and cetylpyridinium chloride (CPC) and L-menthol as penetration enhancers were prepared. The amounts of Chol and CPC were selected as causal factors. Physicochemical characteristics (particle size, size distribution, zeta potential, elasticity and drug content) and an in vitro skin-permeation study of meloxicam-loaded menthosomes were evaluated. The concentrations of MX that permeated the skin at 2-12 h and the flux were selected as response variables. The optimal formulation was estimated using a nonlinear response-surface method incorporating thin-plate spline interpolation. The experimental values were very close to the values predicted by the computer programs in this study. A Bayesian network analysis was applied to gain a mechanistic understanding of the relationships between causal factors and response variables.Key words menthosome; liposome; optimization; skin permeation; meloxicam; menthol For the past few decades, the use of liposomal vesicles in drug-delivery systems for skin permeation has evoked considerable interest and attracted increasing attention. Many reports focus on the use of liposomes for enhancing skin permeation of hydrophilic and lipophilic compounds, proteins and macromolecules. However, recent studies indicate that in most cases, classic liposomes are of little or no value as transdermal drug-delivery carriers because they do not penetrate skin deeply, but rather remain confined to the upper layers of the stratum corneum. Confocal microscopic studies showed that intact fluorescent labeled liposomes were not able to penetrate into the granular layers of the epidermis. 1)Since the first paper to report the effectiveness of deformable liposomes which can be used for skin delivery of drug into deep skin region was published by Cevc and Blume, 2) new categories of vesicles with high elasticity or flexibility, such as transfersomes,3) ethosomes, 4) flexosomes 5) and invasomes 6) have been introduced and developed. These vesicles mainly consist of phospholipids and an edge activator or penetration enhancer in which only a specially designed vesicle was shown to be able to allow transdermal drug delivery. Menthosomes, novel deformable carriers consist of phospholipids, surfactant and menthol were also introduced in this study. Several intensive studies suggested that the permeability of drug in liposomes and their analogues depends on their physicochemical characteristics (e.g., particle size, size distribution, zeta potential, lamellarity, elasticity, drug content, etc.), and these characteristics were dir...

Comparative Study of Novel Ultradeformable Liposomes: Menthosomes, Transfersomes and Liposomes for Enhancing Skin Permeation of Meloxicam

“…12) As shown in Table 1, MX loaded vesicles (menthosomes, transfersomes and liposomes) composed of a controlled amount of MX, PC, and various amounts of Chol as membrane stabilizer, and CPC and MEN as penetration enhancer were prepared. l-menthol was reported to improve the skin permeation of various drugs by increase of drug partition and diffusion.…”

“…However, recent approaches in vesicular modulating drug delivery through skin have resulted in many designs of novel vesicular carriers e.g., deformable liposomes (transfersomes), 7) niosomes, 8) ethosomes, 9) invasomes, 10) flexosomes 11) and menthosomes. 12) Transfersomes are the first generation of elastic vesicles introduced by Cevc and Blune 7) and consist mainly of phospholipids and an edge activator or a single-chain surfactant which having a high radius of curvature that increases deformability of the bilayers. 13) Niosomes are the second generation of elastic vesicles introduced by van den Bergh et al 8) and compose of the optimal ration of non-ionic surfactant and cholesterol.…”

“…14) Moreover, the latest deformable liposomes, menthosomes was developed and introduced by our group. 12) Menthosomes, novel ultradeformable carriers consist of phospholipids, menthol and edge activator. Menthosomes was optimized using a nonlinear response-surface method incorporating thin-plate spline interpolation (RSM-S).…”

“…15,16) The result showed that the estimated values by the computer programs were very close to experimental values. 12) To deliver MX into deep layer of the skin, the most potential liposomal carrier for transdermal delivery was required.…”

Elastic liposomes as novel carriers: recent advances in drug delivery

“…70,87 Table 5 summarizes a review of several drugs reported for transdermal delivery using ELs and recently reported new ELs. [88][89][90][91][92][93][94][95][96][97][98] Furthermore, these latest ELs were tabulated (Table 6) with valuable information, such as definition, composition, classification, advantages, and inherent limitations. 14 …”