Studies on the fabrication and applications of stratum corneum lipids based-particles

Abstract

The stratum corneum lipids are arranged in a lamellar structure and contribute to maintain a healthy, moisturized skin. Their physiological function is to provide adhesion of corneocytes as well as to protect against excessive transepidermal water loss and against environmental irritants. Consequently, these lipids are potential actives for skin treatment. However, due to their limited solubility in dispersion media such as emulsion, only small amount of the lipids have been included in dosage. Thus, for an effect function of lipids on a skin, it is critical to increase the dosage of stratum corneum lipids and to develop new technique to improve the long term stability of stratum corneum lipids in complex formulations. In chapter 1, we review the role of ceramides in normal and diseased skin. Most skin disorders have a diminished barrier function present a decrease in total ceramide content with some differences in the ceramide pattern. Formulations containing stratum corneum lipids, in particular, some ceramides supplementation could improve disturbed skin conditions. In chapter 2, the incorporation of ceramide into an emulsion for skincare treatment was investigated. The formation of emulsions and micelles in water/ceramide PC104/CholEO20/C16EO20 and water/ceramide PC104/CholEO20 mixtures was investigated through the phase behavior studies. The phase diagrams showed the existence of micelle and emulsion regions in both systems. The mixed surfactant system (CholEO20/C16EO20) showed the wider micellar and emulsion regions than the single surfactant system (CholEO20). From FT-IR measurements, it was found that the polyoxyethylene (POE) groups of surfactants formed the hydrogen bonds with amido carbonyl group in ceramide PC104. This result indicated that the hydrophilic part (EO) of surfactants could stabilize the lamellar structure and emulsion of ceramide PC104. The mixed surfactant system (CholEO20/C16EO20) resulted in the smaller emulsion droplet size due to the effect of curvature at the interface, thus further increasing emulsion stability. The mixed surfactant system could incorporate up to 4 wt.% of ceramide PC104 into emulsion more than single surfactant system. In chapter 3, we present a facile and straightforward method to fabricate liposomal membranes with a significantly stable lamellar structure consisting of pseudo-ceramide, fatty acid, and cholesterol. Characterizing their membrane properties, in which we have used differential scanning calorimetry, X-ray diffraction, and FT-IR spectra, enables us to demonstrate that pseudo-ceramide with appropriate amounts of stearic acid and cholesterol can assemble to form a stable lamellar ??-phase. Moreover, we show that cholesterol is indeed important and plays a role in controlling the melting entropy of lipid membranes, which is attributed to a disordered molecular packing, thus creating more flexible liposomal membranes. This approach to use pseudo-ceramide offers a useful means to fabricate a variety of biocompatible liposomes with controllable membrane properties, which enlarges their applicability in the field of drug delivery, dermatology, and cosmetics. In chapter 4, the recovery of skin barrier functions was investigated with pseudo-ceramide-based lipid microparticles. The microparticles were prepared by using a fluid bed technique where lipid components (a pseudo-ceramide, cholesterol and a fatty acid) were coated on a sugar seed, and a polymer was subsequently coated on the lipid microparticles. The microparticles contained large amount of pseudo-ceramide, and the pseudo-ceramide was in the form of lamellar structures mixed with other lipid components. In addition, the microparticles were stably dispersed in aqueous media or emulsion systems without any disruption of the microparticles… structures, thereby supplying sufficient amount of the pseudo-ceramide to skins for improving skin barrier functions such as preventing water loss. Such a role of the microparticles was proven by evaluating in vivo the efficacy of the lipid microparticles in reducing a trans-epidermal water loss (TEWL) of impaired murine skins. As a result, the novel pseudo-ceramide-based lipid microparticles for barrier recovery may potentially be applied in the field of dermatology, cosmetics and pharmaceuticals. In chapter 5, this study was performed to evaluate the effects of moisturizer containing lipid microparticles on atopic dermatitis. Methods: Patients with mild atopic dermatitis (n = 30, aged 5?V19 years) were recruited and instructed to apply a moisturizer containing physiologic lipid microparticles for 4 weeks. The SCORing Atopic Dermatitis (SCORAD) score and general symptoms were evaluated. In addition, stratum corneum (SC) hydration were also measured. Twenty-nine patients completed the study. The SCORAD value decreased dramatically after 4 weeks of moisturizer application (p = 0.000). The general symptoms of atopic dermatitis were also greatly improved. At baseline, most patients reported their symptoms as mild and moderate, but after 4 weeks 20 of the patients (69%) had no symptoms. The SC hydration increased significantly (p = 0.000). No significant adverse effects were observed.