Tuning the Extent and Depth of Penetration of Flexible Liposomes in Human Skin (original) (raw)
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Journal of Drug Targeting, 2008
Novel potential carriers for non-invasive drug delivery were prepared from polyoxyethylene(20) oleyl ether (C 18:1 EO 20) 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 $ R sat e ¼ 0.25 in the bilayer. The surfactant-saturated bilayers exhibit bending rigidity of k c , 2.1 k B T, as determined with an improved vesicle adaptability assay involving analysis of normalised flux density through a nanoporous 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. R sat e , which is linearly proportional to R e 2 R sat e. C 18:1 EO 20-SPC mixed vesicles that can cross narrow pores are arguably suitable for targeted drug delivery across intact skin.
International Journal of Nanomedicine, 2013
Vesicles that are specifically designed to overcome the stratum corneum barrier in intact skin provide an efficient transdermal (systemic or local) drug delivery system. They can be classified into two main groups according to the mechanisms underlying their skin interaction. The first group comprises those possessing highly deformable bilayers, achieved by incorporating edge activators to the bilayers or by mixing with certain hydrophilic solutes. The vesicles of this group act as drug carriers that penetrate across hydrophilic pathways of the intact skin. The second group comprises those possessing highly fluid bilayers, owing to the presence of permeation enhancers. The vesicles of this group can act as carriers of drugs that permeate the skin after the barrier of the stratum corneum is altered because of synergistic action with the permeation enhancers contained in the vesicle structure. We have included a detailed overview of the different mechanisms of skin interaction and discussed the most promising preclinical applications of the last five years of Transfersomes ® (IDEA AG, Munich, Germany), ethosomes, and invasomes as carriers of antitumoral and anti-inflammatory drugs applied by the topical route.
International Journal of Molecular Sciences
Administration of active pharmaceutical ingredients (APIs) through the skin, by means of topical drug delivery systems, is an advanced therapeutic approach. As the skin is the largest organ of the human body, primarily acting as a natural protective barrier against permeation of xenobiotics, specific strategies to overcome this barrier are needed. Liposomes are nanometric-sized delivery systems composed of phospholipids, which are key components of cell membranes, making liposomes well tolerated and devoid of toxicity. As their lipid compositions are similar to those of the skin, liposomes are used as topical, dermal, and transdermal delivery systems. However, permeation of the first generation of liposomes through the skin posed some limitations; thus, a second generation of liposomes has emerged, overcoming permeability problems. Various mechanisms of permeation/penetration of elastic/ultra-deformable liposomes into the skin have been proposed; however, debate continues on their e...
Chemistry and physics of lipids, 2017
Deformability is not just a fundamentally interesting vesicle characteristic; it is also the key determinant of vesicle ability to cross the skin barrier; i.e. skin penetrability. Development of bilayer vesicles for drug and vaccine delivery across the skin should hence involve optimization of this property, which is controllable by the concentration of bilayer softeners in or near the vesicle bilayers. To this end, we propose a simple method for quantifying the effect of bilayer softeners on deformability of bilayer vesicles. The method derives the bending rigidity of vesicle bilayers from vesicle size dependence on softener concentration. To exemplify the method, we studied mixtures of soybean phosphatidylcholine with anionic sodium deoxycholate, non-ionic polyoxyethylene (20) sorbitan oleyl ester (polysorbate 80), or non-ionic polyoxyethylene (20) oleyl ether (C18:1EO20, Brij® 98). With each of the tested bilayer softeners, the bending rigidity of the resulting mixed-amphipat ves...
International Journal of Pharmaceutics, 2014
Chemical compounds studied in this article: Ibuprofen (PubChem CID: 3672) a b s t r a c t Transdermal delivery of active principles is a versatile method widely used in medicine. The main drawback for the transdermal route, however, is the low efficiency achieved in the absorption of many drugs, mostly due to the complexity of the skin barrier. To improve drug delivery through the skin, we prepared and characterized liposomes loaded with ibuprofen and designed pharmaceutical formulations based on the extemporaneous addition of penetration enhancer (PE) surfactants. Afterwards, permeation and release studies were carried out. According to the permeation studies, the ibuprofen liposomal formulation supplemented with PEs exhibited similar therapeutic effects, but at lower doses (20%) comparing with a commercial formulation used as a reference. Atomic force microscopy (AFM) was used to investigate the effect caused by PEs on the adsorption mechanism of liposomal formulations onto the skin. Non-fused liposomes, bilayers and multilayered lipid structures were observed. The transformation of vesicles into planar structures is proposed as a possible rationale for explaining the lower doses required when a liposome formulation is supplemented with surfactant PEs.
Investigation of the mechanism of enhanced skin penetration by ultradeformable liposomes
International Journal of Nanomedicine, 2014
This study aimed to determine the mechanism by which ultradeformable liposomes (ULs) with terpenes enhance skin penetration for transdermal drug delivery of fluorescein sodium, using transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Skin treated with ULs containing d-limonene, obtained from in vitro skin penetration studies, was examined via TEM to investigate the effect of ULs on ultrastructural changes of the skin, and to evaluate the mechanism by which ULs enhance skin penetration. The receiver medium collected was analyzed by TEM and CLSM to evaluate the mechanism of the drug carrier system. Our findings revealed that ULs could enhance penetration by denaturing intracellular keratin, degrading corneodesmosomes, and disrupting the intercellular lipid arrangement in the stratum corneum. As inferred from the presence of intact vesicles in the receiver medium, ULs are also able to act as a drug carrier system. CLSM images showed that intact vesicles of ULs might penetrate the skin via a transappendageal pathway, potentially a major route of skin penetration.
Recent Advances in Elastic Liposomes: Current Status and Future Perspective
Journal of Pharmaceutical Research International, 2021
Elastic liposomse (ELs) are the flexible liposomes formulated using phospholipids as well as edge activators. Edge activators provide elasticity to the Els. Els provide advantages over other formulations and have the ability to be delivered by different routes such as topical, transdermal, nasal, ocular, etc. Potential of encapsulating not only lipophillic but also hydrophillic drugs in a single vesicle, ability to pass through channels 1/10th of their diameter, increase in drug permeation, enhanced solubility of drug, patient compliance, prevention of degradation of drug makes them efficient carriers of drugs and leads to increased interest of researchers in them. This review provides understanding of composition of Els, advantages, method of preparation and the adaptable role played by ELs in the administration of numerous drugs for different diseases.
Liposomes can both enhance or reduce drugs penetration through the skin
Scientific Reports, 2018
The adequate formulation of topical vehicles to treat skin diseases is particularly complex. A desirable formulation should enhance the accumulation of the active drugs in the target tissue (the skin), while avoiding the penetration enhancement to be so large that the drugs reach the systemic circulation in toxic amounts. We have evaluated the transcutaneous penetration of three drugs chosen for their widely variable physicochemical properties: Amphotericin B, Imiquimod and Indole. We incorporated the drugs in fluid or ultra-flexible liposomes. Ultra-flexible liposomes produced enhancement of drug penetration into/through human skin in all cases in comparison with fluid liposomes without detergent, regardless of drug molecular weight. At the same time, our results indicate that liposomes can impede the transcutaneous penetration of molecules, in particular small ones.
The Scientific World Journal, 2012
This study focuses on the effect of different flexible liposomes containing sodium cholate, Tween 80, or cineol on skin deposition of carboxyfluorescein (CF). Size distribution, morphology, zeta potential, and stability of the prepared vesicles were evaluated. The influence of these systems on the skin deposition of CF utilizing rat skin as membrane model was investigated. Results showed that all of the investigated liposomes had almost spherical shapes with low polydispersity (PDI < 0.3) and particles size range from 83 to 175 nm. All liposomal formulations exhibited negative zeta potential, good drug entrapment efficiency, and stability. In vitro skin deposition data showed that flexible liposomes gave significant deposition of CF on the skin compared to conventional liposomes and drug solutions. This study revealed that flexible liposomes, containing cineole, were able to deliver higher amount of CF suggesting that the hydrophilic drugs delivery to the skin was strictly correlated to the vesicle composition.
A Comprehensive Review on Preparation, Evaluation and Applications of Deformable Liposomes
Iranian Journal of Pharmaceutical Research : IJPR, 2021
Elastic or deformable liposomes are phospholipid-based vesicular drug delivery systems that help improve the delivery of therapeutic agents through the intact skin membrane due to their deformable characteristics that overcome the problems of conventional liposomes. In the present review, different types of deformable liposomes such as transfersomes, ethosomes, menthosomes, invasomes and transethosome are studied, and their mechanism of action, characterization, preparation methods, and applications in pharmaceutical technology through topical, transdermal, nasal and oral routes for effective drug delivery are compared for their potential transdermal delivery of poorly permeable drugs. Due to the deformable characteristics of these vehicles, it resulted in modulation of increased drug encapsulation efficiency, permeation and penetration of the drug into or through the skin membrane and are found to be more effective than conventional drug delivery systems. So deformable liposomes ca...