Development of novel polyglycerol fatty acid ester-based nanoparticles for the dermal delivery of tocopherol acetate.

The aim of this study was to develop and evaluate novel polyglycerol fatty acid ester (PGFE)-based nanoparticles (NPs) for the dermal delivery of tocopherol acetate (TA). TA-loaded PGFE-based NPs (PGFE-NPs) were prepared by mixing PGFE, soya phosphatidylcholine, dimyristoylphosphatidylglycerol, and TA with film using the film rehydration and extrusion method. The prepared formulations were analyzed by dynamic light scattering, small-angle X-ray diffraction and polarization microscopy. An in vitro skin accumulation test was performed with TA under occlusive and non-occlusive applications, using Yucatan micropig skin. The size range of the TA-loaded liposome and PGFE-NPs was 107-128 nm, and they were encapsulated in 1.6-2.3 mg/mL TA. All PGFE-NP formulations were negatively charged and stable for 2 weeks. Under occlusive applications, all formulations induced small amounts of TA accumulation in the epidermis but not in the dermis. However, under non-occlusive applications, some of PGFE-NP formulations enhanced TA accumulation in the epidermis. Furthermore, only the polyglycerol 4-laurate (PG4L)-based formulation induced dermal TA accumulation with the change in the formulation from a vesicular to bilayer stacked structure following water evaporation under non-occlusive applications. These results indicated that the novel TA-loaded PG4L formulation enabled the dermal delivery of TA in non-occlusive applications.

Association of dry skin with intercellular lipid composition of stratum corneum after erlotinib administration.

PURPOSE: Erlotinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, causes skin disorders such as dry skin, which impairs the skin barrier function. Stratum corneum (SC) lipids play an important role in skin barrier function; therefore, this study aimed to investigate the relationship between erlotinib-related dry skin and changes in the intercellular lipid composition and structure of the SC. METHODS: Overall, 21 patients with non-small lung cancer were enrolled in this study. All patients received 150 mg/day erlotinib orally. A SC sample of each patient was collected from the inner forearm using the tape stripping method on days 0, 7, 14, 28, and 56 after erlotinib administration. The intercellular lipid components of ceramide (CER), free fatty acid (FFA), and cholesterol sulfate (CS) in samples extracted from the tape were analyzed using liquid chromatography/time-of-flight/mass spectrometry. SC samples from six healthy subjects were collected as controls on days 0, 28 and 56 and analyzed similarly. RESULTS: Although total CER and FFA levels were not changed after erlotinib administration, the levels of CER subclasses [AP] and [AH] and hydroxy FFA, which are structural components of CER subclass [A], decreased. In contrast, the CS levels increased after erlotinib administration. Moreover, higher CS levels in the SC correlated with the clinical condition of dry skin. No changes were observed in the SC lipid composition in healthy subjects. CONCLUSION: Erlotinib-related dry skin was associated with a higher CS level in the SC.

Development of phospholipid nanoparticles encapsulating 3-O-cetyl ascorbic acid and tocopherol acetate (TA-Cassome) for improving their skin accumulation.

Phospholipid nanoparticles (PNs) encapsulating vitamin C and E derivatives, 3-O-cetyl ascorbic acid (CA) and tocopherol acetate (TA), respectively, were examined using the film rehydration and extrusion method. PN formulations (TA-Cassome) were prepared by mixing CA, soya phosphatidylcholine (Soya PC), sodium cholate, and TA at a molar ratio of 20/80/5/6. Glycerol (GL) or diglycerol (DG) were also added to improve the skin accumulation of CA and TA. Three TA-Cassome formulations were evaluated using a dynamic light scattering (DLS), NMR, TEM, skin accumulation test for CA and TA, and small-angle X-ray diffraction (SAXD) analysis. TA-Cassome formulations (150 nm) were stable for two weeks and they encapsulated 1.8 mg/mL of TA. TEM and SAXD analysis revealed that the nanoparticles formed a spherical multilayer structure. 1H and 31P NMR indicated that GL and DG enhanced the proton mobility of choline groups of soya PC molecules located on the membrane surface of TA-Cassome. Accumulation of CA and TA in the dermis was increased by adding GL and DG. SAXD analysis revealed that GL and DG promoted the formation of new lamellar structures on the stratum corneum, which contributed to improving the skin accumulation of CA and TA.