Lecithin-based nanoemulsions of traditional herbal wound healing agents and their effect on human skin cells.

In previous studies, lecithin-based nanoemulsions (NEs) have been shown to be skin friendly drug carrier systems. Due to their nontoxic properties, NEs might also be suitable as wound healing agents. Hence, different O/W NEs based on lecithin Lipoid® S 75 and plant oils or medium chain triglycerides were produced and characterised. Two lipophilic natural wound healing agents, a betulin-enriched extract from birch bark (BET) and a purified spruce balm (PSB), were successfully incorporated and their effects on primary human skin cells were studied in vitro. MTT, BrdU and scratch assays uncovered the positive influence of the drug-loaded NEs on cell viability, proliferation and potential wound closure. Compared to control formulations, the NEs loaded with either BET or PSB led to higher cell viability rates of fibroblasts and keratinocytes. Higher proliferative activity of keratinocytes and fibroblasts was observed after the treatment, which is a prerequisite for wound closure. Indeed, in scratch assays NEs with PSB and notably BET showed significantly ameliorated wound closure rates than the negative control (unloaded NEs) and the positive control (NEs with dexpanthenol). Our findings suggest that BET and PSB are outstanding wound healing drugs and their incorporation into lecithin-based NEs may represent a valid strategy for wound care.

Effects of lecithin-based nanoemulsions on skin: Short-time cytotoxicity MTT and BrdU studies, skin penetration of surfactants and additives and the delivery of curcumin.

Surfactants are important ingredients in pharmaceutical and cosmetic formulations, as in creams, shampoos or shower gels. As conventional emulsifiers such as sodium dodecyl sulfate (SDS) have fallen into disrepute due to their skin irritation potential, the naturally occurring lecithins are being investigated as a potential alternative. Thus, lecithin-based nanoemulsions with and without the drug curcumin, known for its wound healing properties, were produced and characterised in terms of their particle size, polydispersity index (PDI) and zeta potential and compared to SDS-based formulations. In vitro toxicity of the produced blank nanoemulsions was assessed with primary human keratinocytes and fibroblasts using two different cell viability assays (BrdU and EZ4U). Further, we investigated the penetration profiles of the deployed surfactants and oil components using combined ATR-FTIR/tape stripping experiments and confirmed the ability of the lecithin-based nanoemulsions to deliver curcumin into the stratum corneum in tape stripping-UV/Vis experiments. All manufactured nanoemulsions showed droplet sizes under 250 nm with satisfying PDI and zeta potential values. Viability assays with human skin cells clearly indicated that lecithin-based nanoemulsions were superior to SDS-based formulations. ATR-FTIR tests showed that lecithin and oil components remained in the superficial layers of the stratum corneum, suggesting a low risk for skin irritation. Ex vivo tape stripping experiments revealed that the kind of oil used in the nanoemulsion seemed to influence the depth of curcumin penetration into the stratum corneum.

Cytotoxicity of lecithin-based nanoemulsions on human skin cells and ex vivo skin permeation: Comparison to conventional surfactant types.

As constituents of cellular membranes, lecithins feature high biocompatibility and great emulsifying properties due to their amphiphilicity. Additionally, there are expectations that these naturally occurring emulsifying agents can replace other skin damaging emulsifiers like sodium dodecyl sulfate or sodium laureth sulfate. However, cytotoxicity data of lecithin-based formulations on primary human skin cells are scarce. Thus, we developed nanoemulsions with different kinds of surfactants (amphoteric, anionic and non-ionic), studied the skin permeation of a model drug from this formulations employing Franz-type diffusion cells and monitored their cytotoxicity potential on primary human keratinocytes and fibroblasts using a cell proliferation assay. The skin diffusion studies demonstrated that the amphoteric lecithin-based emulsifiers were superior to non-ionic surfactants in terms of skin permeation, but inferior to anionic emulsifiers. Further, we found that the nanoemulsions containing the amphoteric lecithins as emulsifying agents lead to significantly higher viability rates of both epidermal keratinocytes and dermal fibroblasts than the investigated anionic and non-ionic surfactants. This renders them a promising alternative to conventional emulsifiers used in daily products.

Natural microemulsions: formulation design and skin interaction.

Microemulsions are thermodynamically stable, colloidal drug delivery systems. This study presents the first substantiated comparison of natural, skin-compatible and biodegradable surfactants in terms of their suitability to form isotropic microemulsions and their skin interaction. Pseudoternery phase diagrams were constructed for lecithin, sucrose laurate and alkylpolyglycoside as single surfactants. Moreover, also mixed surfactant films of lecithin and alkylpolyglycoside as well as lecithin and sucrose laurate were tested. Large isotropic areas could be identified for lecithin, sucrose laurate and lecithin-sucrose laurate. One defined composition was chosen from the pseudoternery phase diagram, prepared with all investigated surfactants and 1:1 surfactant mixtures, respectively, and analysed for their effect on the stratum corneum on a molecular level by ATR-FTIR. Significantly higher frequency values of the symmetric and asymmetric CH(2)-stretching bands compared to the control were recorded for all microemulsions, indicating a hexagonal arrangement of the lipid chains. A similar trend was observed for the lateral packing of the alkyl chains as suggested by the shift of the CH(2)-scissoring bands. Moreover, diffusion cell experiments using porcine skin were performed with the two model drugs flufenamic acid and fluconazole. In both cases, the lecithin-based microemulsions showed the highest permeation rates followed by the alkylpolyglycoside-lecithin microemulsions.

Development of sucrose stearate-based nanoemulsions and optimisation through γ-cyclodextrin.

Nanoemulsions aimed at dermal drug delivery are usually stabilised by natural lecithins. However, lecithin has a high tendency towards self-aggregation and is prone to chemical degradation. Therefore, the aim of this study was to develop nanoemulsions with improved structure and long-term stability by employing a natural sucrose ester mixture as sole surfactant. A thorough comparison between the novel sucrose stearate-based nanoemulsions and corresponding lecithin-based nanoemulsions revealed that the sucrose ester is superior in terms of emulsifying efficiency, droplet formation as well as physical and chemical stability. The novel formulations exhibited a remarkably homogeneous structure in cryo TEM investigations, as opposed to the variable structure observed for lecithin-based systems. The in vitro skin permeation rates of lipophilic drugs from sucrose stearate nanoemulsions were comparable to those obtained with their lecithin-based counterparts. Furthermore, it was observed that addition of γ-cyclodextrin led to enhanced skin permeation of the steroidal drug fludrocortisone acetate from 9.99±0.46 to 55.10±3.67 µg cm(-2) after 24 h in the case of sucrose stearate-based systems and from 9.98±0.64 to 98.62±24.89 µg cm(-2) after 24 h in the case of lecithin-based systems. This enhancement effect was significantly stronger in formulations based on lecithin (P<0.05), which indicates that synergistic mechanisms between the surfactant and the cyclodextrin are involved. Cryo TEM images suggest that the cyclodextrin is incorporated into the interfacial film, which might alter drug release rates and improve the droplet microstructure.

Skin-compatible lecithin drug delivery systems for fluconazole: effect of phosphatidylethanolamine and oleic acid on skin permeation.

The purpose of the present study was to evaluate skin-compatible drug delivery systems for fluconazole. Pseudoternary phase diagrams were constructed, composed of different soybean lecithins/oil/isopropanol and water. The role of the various lecithin compositions was expressed in the different resulting isotropic areas. Based on these phase diagrams, two systems were chosen as drug delivery systems for fluconazole. The influence of phosphatidylethanolamine and of the oil component on the skin permeation of fluconazole was investigated. The more phosphatidylethanolamine, the greater was the fluconazole skin permeation, independent of the hydrophilicity of the system. The influence of oleic acid and isopropylmyristate as the oil component was compared and a greater penetration enhancing effect was found for the microemulsion containing oleic acid.