Liposomes skin penetration

Liposomes applied on the skin were also investigated for their delivery proprieties to the pilosebaceous units [15,23 28]. The in vitro skin penetration behavior of carboxyfluorescein incorporated in multilamellar liposomes (phosphatidylcholine cholesterol phosphatidylser-ine) and in another four nonliposomal systems (HEPES pH 7.4 buffer 5% propylene glycol 10% ethanol and 0.05% sodium lauryl sulfate) was studied by Lieb et al. [25]. Using two fluorescent techniques the authors found a higher accumulation of the probe within skin follicles when delivered from liposomes [25], Further, in an interesting setup of in vitro and in vivo experiments in mice, Hoffman s group observed liposomal delivery of the active Lac-Z gene and its expression mostly in the hair follicles [26,28]. 

Fahr, A., Schafer, U., Verma, D.D. et al. Skin penetration enhancement of substances by a novel type of liposomes. SOFW Journal 2000 126 49-53. 

Verma, D.D., Verma, S., Blume, G. et al. Liposomes increase skin penetration of entrapped and non-entrapped hydrophilic substances into human skin a skin penetration and confocal laser scanning microscopy study. Eur. J. Pharm. Biopharm. 2003 55 271-7. 

Key words Colloids, Elastic liposomes, Liposomes, Transfersomes, Skin penetration enhancement. Drug carriers... 

El Maghraby GM, Williams AC, Barry BW (2004) Interactions of surfactants (edge activators) and skin penetration enhancers with liposomes. Int J Pharm 276(1-2) 143-161... 

In a subsequent study, van Hal et al. [40] reported that a decrease in cholesterol content in liquid state bilayers, which increases bilayer fluidity, resulted in an increase in estradiol transport across SC. With confocal laser scanning microscopy, Meuwissen et al. examined the diffusion depth of gel- vs. liquid-state liposomes labeled with fluorescein-dipalmitoylphosphatidylethanolamine (fluorescein-DPPE) with human skin in vitro [41] (Figure 3) and rat skin in vivo [42] and found that the lipophilic label when applied in liquid-state bilayers onto the skin penetrated deeper into the skin than when applied in gel-state liposomes. Recently, Fresta and Puglisi [43] reported that corticosteroid dermal delivery with skin-lipid liposomes was more effective than delivery with phospholipid vesicles, both with respect to higher drug concentrations in deeper skin layers and therapeutic effectiveness. This is a very surprising result, because skin lipid liposomes are rigid and form stacks of lamellae on the surface of the skin [44]. From the previously mentioned studies it seems clear that the thermodynamic state of the bilayer plays a crucial role in the effect of vesicles on dmg transport rate across skin in vitro. 

Gillet A., Compere R, Lecomte F., Hubert R, Ducat E., Evrard B., Riel G. (2011). Liposome surface charge influence on skin penetration behaviour. Int hann., 411,223-231. 

Reservoir delivery systems have been developed in a variety of styles, ranging from microcapsules to hollow fibers to liposomes. Hayashi et al. (1994) produced delivery systems by encapsulating proteins and hormones inpoly-L-lactide microspheres by a solvent evaporation method. The release mechanism for hormones entrapped in liposomes was studied by Ho et al (1986). Progesterone and hydrocortisone skin permeation was enhanced by the presence ofthe liposomes no penetration ofthe liposomes was observed. Examples ofthe most common hydrogels employed in reservoir systems are crystalline-rubbery PEG, PAAm, celluloses, PAA, and PHEMA. 

Although ciclosporin and tacrolimus applied systemically improve psoriatic lesions, they are clearly less active when applied topically. Therefore, liposomal preparations have been developed. Indeed, ciclosporin penetrates deeper strata of rodent and human cadaver skin more efficiently when incorporated into liposomes [51], Moreover, tacrolimus concentrations in murine skin have increased ninefold, and skin graft survival prolonged, if the drug is liposome encapsulated [52]. This indicates that topical psoriasis therapy with tacrolimus may become possible. At present, topical tacrolimus is confined to the less recalcitrant forms of mild eczema. 

Liposome-encapsulated tretinoin has been tested in hairless mice as well as in man. The animal experiment has demonstrated the favorable uptake of the retinoid, whereas the liposomal lipids appear to be more retained in the homy layer [53], Moreover, with phospholipid-based liposomes belonging to the gel-state type, tretinoin penetration in murine skin appears to be confined to the epidermis [54] and, thus, is close to prednicarbate penetration described above. In patients with acne vulgaris, we could demonstrate a better tolerability of liposomal tretinoin as compared to a commercial gel while efficiency remains the same [55],... 

Michel, C., et al.. Penetration of spin-labeled retinoic acid from liposomal preparations into the skin of SKHl hairless mice measurement by EPR tomography. Int. J. Pharm., 98, 131-39, 1993. 

Lasch, J., Laub, R., and Wohlrab, W. (1991). How deep do intact liposomes penetrate into human skin J. Contrail. Release, 18, 55-8. 

Cevc G. Transfersomes, liposomes and other lipid suspensions on the skin permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug... 

Many studies have employed phospholipids as liposomes (vesicles) to transport drugs into and through human skin. However, a few investigations have also employed phospholipids in a nonvesicular form as penetration enhancers. For example, 1% phosphatidylcholine in PG, a concentration at which liposomes would not form, enhanced theophylline penetration through hairless mouse skin [64]. Similarly, indomethacin flux was enhanced through rat skin by the same phospholipid and hydrogenated soybean phospholipids increased diclofenac permeation through rat skin in vivo. 

Dermal and transdermal delivery requires efficient penetration of compounds through the skin barrier, the bilayer domains of intercellular lipid matrices, and keratin bundles in the stratum corneum (SC). Lipid vesicular systems are a recognized mode of enhanced delivery of drugs into and through the skin. However, it is noteworthy that not every lipid vesicular system has the adequate characteristics to enhance skin membrane permeation. Specially designed lipid vesicles in contrast to classic liposomal compositions could achieve this goal. This chapter describes the structure, main physicochemical characteristics, and mechanism of action of prominent vesicular carriers in this field and reviews reported data on their enhanced delivery performance. 

An early study confirmed that occlusion is detrimental to transfersome penetration enhancement ability. The results of this study clearly demonstrated that, under the occlusive conditions, murine skin permeation of fluorescently labeled lipids from transfersomal suspensions and liposomes is comparable [67]. Furthermore, Guo et al. reported that the vesicles failed to transfer detectable quantities of cyclosporin A through the hydrated abdominal mice skin [71],... 

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