The influence of microemulsion structure on their skin irritation and phototoxicity potential.

The purpose of this study was to examine skin irritation and phototoxicity potentials of several microemulsions (ME), all comprising approximately the same percentage of surfactant mixture, but varying oil/water content and consequently inner structure being either droplet-like (o/w ME, o/w ME carbomer, w/o ME and w/o ME white wax) or lamellar (gel-like ME). Two different in vitro methods were used: MTT assay (performed either on reconstructed human epidermis (RHE) or NCTC 2544 cells) and pig ear test. Neither assay revealed the difference among ME with droplet-like structure. Then again, pig ear test and MTT assay performed on RHE indicated that gel-like ME is more irritant compared to other tested ME, whereas no difference among formulations were observed by MTT assay on NCTC 2544 cells. The reasonable explanation is destruction and consequently uniform structure of ME upon dilution that is inevitable for testing on cell cultures. The results of phototoxicity test again indicated the increased potential of gel-like ME to cause adverse effects on skin. It can be concluded that for ME consisting of the same amount of identical surfactants but having different structure the latter represent a crucial factor that determines their dermal toxicity.

Prolonged subcutaneous delivery of low molecular weight heparin based on thermoresponsive hydrogels with chitosan nanocomplexes: Design, in vitro evaluation, and cytotoxicity studies.

Low molecular weight heparins (LMWHs) have risen in popularity over the past decades. Owing to their appropriate pharmacokinetic profile, they enable long-term clinical applications, e.g. prophylaxis of deep vein thrombosis. Although the administration of LMWHs is not as frequent as of heparin, it still requires once daily injection at least. In order to prolong LMWH release, and thus provide less frequent subcutaneous administration, we designed and thoroughly evaluated thermoresponsive poloxamer-based systems combined with LMWH/chitosan pH-responsive nanocomplexes. A LMWH/chitosan mass ratio of 1:2 was the most appropriate for preparation of small, homogenous and stable nanocomplexes. Thermoresponsive hydrogels were examined by gelation temperature and time, thermal analysis, gel dissolution, LMWH release, and cytotoxicity in vitro. Hydrogels' behaviour was significantly shifted by gel composition e.g. the addition of hydroxypropylmethylcellulose to poloxamer-based systems decreased gelation temperature and time (from 28.6°C to 25.1°C and from 50s to 44s, respectively), but prolonged gel dissolution and LMWH release (7 and 4 days, respectively). Prolongation of drug release was additionally achieved with incorporation of LMWH/chitosan nanocomplexes into the gelling systems. As formulations demonstrated no cytotoxicity in vitro, it may be concluded that these double-responsive platforms are promising candidates for prolonged subcutaneous LMWH delivery during long-term treatment.

The design, synthesis, and antioxidant activity of amphiphilic oximes and amidoximes.

New amphiphilic benzamidoxime, benzoxime, and aliphatic oxime derivatives of glycolipid mimetics were synthesized. The total antioxidant capacity of these amphiphilic derivatives was evaluated using DPPH assay. The observed antioxidant activity was the highest for benzamidoxime derivatives and glycolipid mimetics with two oxime functionalities, followed by benzoxime derivatives, glycolipid mimetics with one oxime group, and dimers of oxime. Due to their amphiphilic structure, which was a guidance for compound design and synthesis, these novel amphiphilic compounds can be proposed as potential antioxidants for tackling oxidative processes in two-phase systems, either biological (cell membranes) or artificial (emulsions).

Lecithin based lamellar liquid crystals as a physiologically acceptable dermal delivery system for ascorbyl palmitate.

Liquid crystalline systems with a lamellar structure have been extensively studied as dermal delivery systems. Ascorbyl palmitate (AP) is one of the most studied and used ascorbic acid derivatives and is employed as an antioxidant to prevent skin aging. The aim of this study was to develop and characterize skin-compliant dermal delivery systems with a liquid crystalline structure for AP. First, a pseudoternary phase diagram was constructed using Tween 80/lecithin/isopropyl myristate/water at a Tween 80/lecithin mass ratio of 1/1, and the region of lamellar liquid crystals was identified. Second, selected unloaded and AP-loaded lamellar liquid crystal systems were physicochemically characterized with polarizing optical microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheology techniques. The interlayer spacing and rheological parameters differ regarding quantitative composition, whereas the microstructure of the lamellar phase was affected by the AP incorporation, resulting either in additional micellar structures (at 25 and 32 °C) or being completely destroyed at higher temperature (37°C). After this, the study was oriented towards in vitro cytotoxicity evaluation of lamellar liquid crystal systems on a keratinocyte cell line. The results suggest that the lamellar liquid crystals that were developed could be used as a physiologically acceptable dermal delivery system.

Main approaches for delivering antioxidant vitamins through the skin to prevent skin ageing.

INTRODUCTION: One of the major contributions to skin photoageing and diseases is oxidative stress, caused by UV radiation inducing reactive oxygen and nitrogen species. Successful prophylaxis and therapy would necessitate control of the oxidant/antioxidant balance at the affected site, which can be achieved through the external supply of endogenous antioxidants. AREAS COVERED: This review discusses possible strategies for dermal delivery of the antioxidant vitamins E and C, as oral supplementation has proved insufficient. These antioxidants have low skin bioavailability, owing to their poor solubility, inefficient skin permeability, or instability during storage. These drawbacks can be overcome by various approaches, such as chemical modification of the vitamins and the use of new colloidal drug delivery systems. New knowledge is included about the importance of: enhancing the endogenous skin antioxidant defense through external supply; the balance between various skin antioxidants; factors that can improve the skin bioavailability of antioxidants; and new delivery systems, such as microemulsions, used to deliver vitamins C and E into the skin simultaneously. EXPERT OPINION: A promising strategy for enhancing skin protection from oxidative stress is to support the endogenous antioxidant system, with antioxidants containing products that are normally present in the skin.

A new approach for increasing ascorbyl palmitate stability by addition of non-irritant co-antioxidant.

The aim of this work was to test innovative approach for enhancing ascorbyl palmitate stability in microemulsions for topical application by addition of newly synthesized co-antioxidant 4-(tridecyloxy)benzaldehyde oxime (TDBO) and to investigate its antioxidant activity and finally to evaluate cytotoxicity of TDBO-loaded microemulsions on keratinocyte cells. TDBO significantly increased ascorbyl palmitate stability in oil-dispersed-in-water (o/w) microemulsions, most presumably due to reduction of ascorbyl palmitate radical back to ascorbyl palmitate, since TDBO free-radical scavenging activity was confirmed. Cytotoxicity experiments demonstrated no significant change in cell viability or morphology in the presence of TDBO-loaded microemulsions regarding unloaded microemulsions, although greater cytotoxicity was observed with increased microemulsion concentrations. Therefore, the incorporation of TDBO as non-cytotoxic co-antioxidant in o/w microemulsions is a promising new strategy for enhancing ascorbyl palmitate stability that could be used to support antioxidant network in the skin.

Dual influence of colloidal silica on skin deposition of vitamins C and E simultaneously incorporated in topical microemulsions.

BACKGROUND: Colloidal silica is the thickener of interest for topical formulations and can therefore be used to optimize the viscosity of both hydrophilic and lipophilic microemulsions (MEs). To the best of our knowledge, no information is available about the effect of topically applied colloidal silica on skin penetration of drugs. So, our aim was to determine its influence on the effectiveness of ME in the simultaneous delivery of vitamins C and E to the skin. METHODS: Two different aspects of silica possible function were investigated. Its effects on formulation characteristics were studied by determination of partition coefficient of the vitamins, their solubility and release profile. The direct impact of silica on the skin was further evaluated by transepidermal water loss measurements, scanning electron microscopy (SEM), and cell toxicity determination (MTT assay). RESULTS: The addition of colloidal silica to ME was shown to increase significantly the vitamins' solubility and their partition to the phase in which they were less soluble. Its presence also increased the amount of both vitamins in epidermis, which was confirmed by release studies. Furthermore, we demonstrated that colloidal silica interacts with excised skin. It decreased transepidermal water loss, probably by retaining water in the stratum corneum because of its massive accumulation in the upper layers, as revealed by SEM. CONCLUSION: The results confirmed that addition of colloidal silica in ME simultaneously loaded with vitamins C and E enhanced vitamins' skin bioavailability by its dual influence on delivery characteristics of ME as well as on skin properties.