Gelen Rodríguez

Conformational Changes in Stratum Corneum Lipids by Effect of Bicellar Systems

Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was applied to study the effects of the bicelles formed by dimyristoyl-glycero-phosphocholine (DMPC) and dihexanoyl-glycero-phosphocholine (DHPC) in porcine stratum corneum (SC) in vitro. A comparison of skin samples treated and untreated with bicelles at different temperatures was carried out. The analysis of variations after treatment in the position of the symmetric CH2 stretching, CH2 scissoring, and CH2 rocking vibrations reported important information about the effect of bicelles on the skin. Bicellar systems caused a phase transition from the gel or solid state to the liquid crystalline state in the lipid conformation of SC, reflecting the major order-disorder transition from hexagonally packed to disordered chains. Grazing incidence small and wide X-ray scattering (GISAXS and GIWAXS) techniques confirmed this effect of bicelles on the SC. These results are probably related to with the permeabilizing effect previously described for the DMPC/DHPC bicelles.

Bicelles: Lipid Nanostructured Platforms with Potential Dermal Applications

Bicelles emerge as promising membrane models, and because of their attractive combination of lipid composition, small size and morphological versatility, they become new targets in skin research. Bicelles are able to modify skin biophysical parameters and modulate the skins barrier function, acting to enhance drug penetration. Because of their nanostructured assemblies, bicelles have the ability to penetrate through the narrow intercellular spaces of the stratum corneum of the skin to reinforce its lipid lamellae. The bicelle structure also allows for the incorporation of different molecules that can be carried through the skin layers. All of these characteristics can be modulated by varying the lipid composition and experimental conditions. The remarkable versatility of bicelles is their most important characteristic, which makes their use possible in various fields. This system represents a platform for dermal applications. In this review, an overview of the main properties of bicelles and their effects on the skin are presented.

Bicellar systems for in vitro percutaneous absorption of diclofenac

This work evaluates the effect of different bicellar systems on the percutaneous absorption of diclofenac diethylamine (DDEA) using two different approaches. In the first case, the drug was included in bicellar systems, which were applied on the skin and, in the second case, the skin was treated by applying bicellar systems without drug before to the application of a DDEA aqueous solution. The characterization of bicellar systems showed that the particle size decreased when DDEA was encapsulated. Percutaneous absorption studies demonstrated a lower penetration of DDEA when the drug was included in bicellar systems than when the drug was applied in an aqueous solution. This effect was possibly due to a certain rigidity of the bicellar systems caused by the incorporation of DDEA. The absorption of DDEA on skin pretreated with bicelles increased compared to the absorption of DDEA on intact skin. Bicelles without DDEA could cause certain disorganization of the SC barrier function, thereby facilitating the percutaneous penetration of DDEA subsequently applied. Thus, depending on their physicochemical parameters and on the application conditions, these systems have potential enhancement or retardant effects on percutaneous absorption that result in an interesting strategy, which may be used in future drug delivery applications.

Application of Bicellar Systems on Skin: Diffusion and Molecular Organization Effects

The effect of bicelles formed by dipalmitoylphosphatidylcholine (DPPC)/dihexanoylphosphatidylcholine (DHPC) on stratum corneum (SC) lipids was studied by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy at different temperatures. Analysis of the lipid organization in terms of chain conformational order and lateral packing shows that the use of bicelles hampers the fluidification of SC lipids with temperature and leads to a lateral packing corresponding to a stable hexagonal phase. Grazing incidence small- and wide-angle X-ray scattering (GISAXS and GIWAXS) techniques confirm these results and give evidence of higher lamellar order after treatment with these bicelles. Additionally, the effects of DPPC/DHPC and dimyristoylphosphatidylcholine (DMPC)/DHPC bicelles at different SC depths were compared. The combination of ATR-FTIR spectroscopy and the tape-stripping method was very useful for this purpose.

Lipid Nanostructures: Self-Assembly and Effect on Skin Properties

This work evaluates the relation between the composition and the self-assembly of some lipid aggregates with their effects on the skin. To this end, liposomes, bicelles and micelles formed by dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC) were characterized by electron microscopy and dynamic light scattering techniques, and applied on the skin. The results revealed that nanostructures with similar assembly but different composition caused different effects on the skin parameters. In general, samples containing DMPC affected the barrier function to a greater extent than systems containing DPPC. Additionally, our results showed that samples with the same lipid composition but different assembly exerted different effects on the skin. Liposomes decreased or did not modify the transepidermal water loss (TEWL), while bicelles and micelles increased this parameter. Hydration of the skin diminished especially after the application of micellar and bicellar samples. In vitro experiments showed structures like vesicles inside cutaneous SC (stratum corneum) incubated with DPPC/DHPC bicelles. These structures were not detected in SC samples incubated with DMPC/DHPC bicelles probably due to the different thermotropic behavior of DMPC and DPPC at physiological temperatures. Results reported in this work should be considered in terms of design of more efficient and specific skin delivery systems.

Barrier function of intact and impaired skin: percutaneous penetration of caffeine and salicylic acid

Background  Normally, percutaneous absorption tests are carried out using skin biopsies for an apparent and acceptable physiological condition. However, under different pathological conditions, the stratum corneum (SC) barrier function is impaired.

Bicosomes: Bicelles in dilute systems

Bicelles are discoidal phospholipid nanostructures at high lipid concentrations. Under dilute conditions, bicelles become larger and adopt a variety of morphologies. This work proposes a strategy to preserve the discoidal morphology of bicelles in environments with high water content. Bicelles were formed in concentrated conditions and subsequently encapsulated in liposomes. Later dilution of these new structures, called bicosomes, demonstrated that lipid vesicles were able to isolate and protect bicelles entrapped inside them from the medium. Characterization of systems before and after dilution by dynamic light-scattering spectroscopy and cryo-transmission electron microscopy showed that free bicelles changed in size and morphology, whereas encapsulated bicelles remained unaltered by the effect of dilution. Free and entrapped bicelles (containing the paramagnetic contrast agent gadodiamide) were injected into rat brain lateral ventricles. Coronal and sagittal visualization was performed by magnetic resonance imaging. Whereas rats injected with free bicelles did not survive the surgery, those injected with bicosomes did, and a hyperintensity effect due to gadodiamide was observed in the cerebrospinal fluid. These results indicate that bicosomes are a good means of preserving the morphology of bicelles under dilution conditions.

Bicellar systems as modifiers of skin lipid structure.

The characterization of different bicellar aggregates and the effects of these systems on the stratum corneum (SC) microstructure have been studied. Dynamic light scattering (DLS) and freeze fracture electron microscopy (FFEM) techniques showed that both of the systems studied, dimyristoyl-phosphatidylcholine/dihexanoyl-phosphocholine (DMPC/DHPC) and dipalmitoyl-phosphocholine (DPPC)/DHPC, were formed by small discoidal aggregates at room temperature (20°C). Treating skin with DMPC/DHPC bicelles does not affect the SC lipid microstructure, whereas bicellar systems formed by DPPC and DHPC can promote the formation of new structures in the SC lipid domains. This indicates the passage of lipids from bicelles through the SC layers and also a possible interaction of these lipids with the SC lipids. Given the absence of surfactant in the bicellar composition and the small size of these structures, the use of these smart nano-systems offers great advantages over other lipid systems for dermatological purposes. Bicelles could be promising applications as drug carriers through the skin. This contribution, based on the new biological use of bicelles, may be useful to scientists engaged in colloid science and offers a new tool for different applications in skin and cosmetic research.

A rhenium tris-carbonyl derivative as a model molecule for incorporation into phospholipid assemblies for skin applications.

A rhenium tris-carbonyl derivative (fac-[Re(CO)3Cl(2-(1-dodecyl-1H-1,2,3,triazol-4-yl)-pyridine)]) was incorporated into phospholipid assemblies, called bicosomes, and the penetration of this molecule into skin was monitored using Fourier-transform infrared microspectroscopy (FTIR). To evaluate the capacity of bicosomes to promote the penetration of this derivative, the skin penetration of the Re(CO)3 derivative dissolved in dimethyl sulfoxide (DMSO), a typical enhancer, was also studied. Dynamic light scattering results (DLS) showed an increase in the size of the bicosomes with the incorporation of the Re(CO)3 derivative, and the FTIR microspectroscopy showed that the Re(CO)3 derivative incorporated in bicosomes penetrated deeper into the skin than when dissolved in DMSO. When this molecule was applied on the skin using the bicosomes, 60% of the Re(CO)3 derivative was retained in the stratum corneum (SC) and 40% reached the epidermis (Epi). Otherwise, the application of this molecule via DMSO resulted in 95% of the Re(CO)3 derivative being in the SC and only 5% reaching the Epi. Using a Re(CO)3 derivative with a dodecyl-chain as a model molecule, it was possible to determine the distribution of molecules with similar physicochemical characteristics in the skin using bicosomes. This fact makes these nanostructures promising vehicles for the application of lipophilic molecules inside the skin.

Bicellar systems as new delivery strategy for topical application of flufenamic acid

In this work, bicellar systems, bilayered disc-shaped nanoaggregates formed in water by phospholipids, are proposed as a novel strategy for delivery of the anti-inflammatory flufenamic acid (FFA) to the skin. A comparative percutaneous penetration study of this drug in bicellar systems and other vehicles was conducted. The effects induced on the skin by the application of FFA in the different vehicles were analyzed by attenuated total reflectance-fourier transform infrared (ATR-FTIR). Additionally, using the microscopic technique freeze-substitution transmission electron microscopy (FSTEM) and X-ray scattering technique using synchrotron radiation (SAXS-SR), we studied the possible microstructural and organizational changes that were induced in the stratum corneum (SC) lipids and the collagen of the skin by the application of FFA bicellar systems. Bicellar systems exhibited a retarder effect on the percutaneous absorption of FFA with respect to the other vehicles without promoting disruption in the SC barrier function of the skin. Given that skin disruption is one of the main effects caused by inflammation, prevention of disruption and repair of the skin microstructure should be prioritized in anti-inflammatory formulations.