Vânia Rodrigues Leite-Silva

Performance evaluation of Cryo Laser Phoresis technique as biophysical method to promote diclofenac sodium cutaneous perfusion

Aiming to alter and/or improve permeation of active compounds in the skin, many strategies have been developed, including biophysical methods. One of the physical absorption techniques, currently known as Cryo Laser Phoresis (CLP), consists of an apparatus that emits radiation on polar or nonpolar molecules of the active substance, resulting in faster penetration when in comparison to the standard topical application. The goal of this work was to evaluate the efficacy of a method that proposes to increase cutaneous permeation of diclofenac sodium by using CLP technique. The influence on permeation was evaluated ex vivo, using Franz cell and human skin obtained from cosmetic surgery. The results were evaluated using statistical methods and data exploratory analysis: clusters, k-means and Principal Component Analysis. The results showed a larger increase in the concentration of diclofenac sodium in the dermis with the use of laser. In all samples (with or without laser application) it was observed that skin surface showed an amount of diclofenac sodium and that there was no active passage to the receptor liquid, suggesting that diclofenac sodium was not absorbed. These results indicate that CLP, when used under the conditions described in this study, is able to increase diclofenac sodium penetration and its retention into deeper layers.

UVA and UVB formulation phototoxicity in a three-dimensional human skin model: Photodegradation effect

In vitro three-dimensional human skin models are an innovative alternative to evaluate cytotoxicity and phototoxicity in the cosmetic industry. The aim of this study was to use a skin model to evaluate the potential toxicity of sunscreen formulations with or without exposure to UV radiation. In addition, the toxicity of these formulations was evaluated after exposure to photodegradation. The results showed toxicity with all formulations/conditions tested, including the control formulation, compared to PBS. Cell viability of photodegraded formulations - prior to the phototoxicity radiation process - was higher, indicating that some formulation components were degraded into products with reduced toxicity. The results also indicated that avobenzone was more unstable/toxic than octyl p-methoxycinnamate under the same test conditions. The sunscreens and their formulations were shown to be toxic to skin model cells to some extent, even when not exposed to UV irradiation; however the biological role of this toxicity is unclear. This result shows the importance of testing sunscreen formulations in real in-use conditions. Finally, since we used an in vitro assay based on a human cell model, this non-invasive technique represents a suitable alternative to animal models for phototoxicity tests in general and could have application in screening new sunscreen products.

Development and Evaluation of Lipid Nanoparticles Containing Natural Botanical Oil for Sun Protection: Characterization and in vitro and in vivo Human Skin Permeation and Toxicity

The use of sunscreen products is widely promoted by schools, government agencies, and health-related organizations to minimize sunburn and skin damage. In this study, we developed stable solid lipid nanoparticles (SLNs) containing the chemical UV filter octyl methoxycinnamate (OMC). In parallel, we produced similar stable SLNs in which 20% of the OMC content was replaced by the botanical urucum oil. When these SLNs were applied to the skin of human volunteers, no changes in fluorescence lifetimes or redox ratios of the endogenous skin fluorophores were seen, suggesting that the formulations did not induce toxic responses in the skin. Ex vivo (skin diffusion) tests showed no significant penetration. In vitro studies showed that when 20% of the OMC was replaced by urucum oil, there was no reduction in skin protection factor (SPF), suggesting that a decrease in the amount of chemical filter may be a viable alternative for an effective sunscreen, in combination with an antioxidant-rich vegetable oil, such as urucum. There is a strong trend towards increasing safety of sun protection products through reduction in the use of chemical UV filters. This work supports this approach by producing formulations with lower concentrations of OMC, while maintaining the SPF. Further investigations of SPF in vivo are needed to assess the suitability of these formulations for human use.

The Influence of Emollients on Dermal and Transdermal Drug Delivery

Emollients are widely used to supplement or replace sebum and provide skin repair and skin penetration enhancement. Their key function is to deliver a lipid film to the surface of the skin, which both lubricates the skin and provides a soothing action and, at the same time, retards transepidermal water loss, promoting skin hydration. An emollient is also characterized by its substantivity, that is, its ability to be retained by the skin after exposure to water, perspiration, friction, and other daily activities. A range of emollients exists, and these can both promote and retard skin penetration. However, in most cases, their effects are to promote skin penetration. There is an increasing need to have emollient products which prolong the skin retention but inhibit the skin penetration of certain actives, such as sunscreens. We also consider how practical formulation can be used to enable appropriate emollients and their formulations to provide both appropriate sensory softness and subtleness, but at the same time, appropriate control of the skin penetration of actives.

Chapter 46 – Skin Penetration

The cosmetic industry continues to expand worldwide. The claims described on a cosmetic product label or in promotional material must be substantiated with scientific data or clinical studies, ensuring that the product actually has the promised effect. Cosmetics must be safe to use over a long term, so safety assurance is critical. Testing the skin penetration of cosmetic actives and excipients is one example of the safety measures that are required. With the prohibition of animal testing for cosmetic evaluation in Europe, product safety has had to be assessed by in vitro methods or in vivo human studies. This has led to a new set of challenges to find and validate in vitro techniques that reliably predict in vivo human responses.

Impact of stirring speed, glycerin and sodium chloride concentrations on photoprotective nanoemulsions: Impacto da velocidade de agitação, contração de glicerina e de cloreto de sódio em nanoemulsões fotoprotetoras

New technologies that improve the physical as the sensory properties of sunscreens can help to increase its continued use and impact on health. The use of nanoemulsions in the development of photoprotective vehicles is an advantage, since nanostructured components may have superior properties regarding their performance when compared to conventional products. The advantages of using nanobiotechnology in manufacture of cosmetic and dermatological formulations arise from the protection of compounds from chemical or enzymatic degradation, from the control of their release, and also to the prolonged retention time of cosmetic ingredients in the stratum corneum. Thus, this study aimed to evaluate the impact of stirring speed and of glycerin and sodium chloride concentrations in the development and effectiveness of a nanoemulsion containing ethylhexyl methoxycinnamate and benzophenone-3. The results of statistical analyses regarding the impact of the variables in the process of nanoemulsion development showed that these parameters affect the phase inversion temperature (PIT). However, this did not affect the particle size and the photoprotective efficacy in vitro. Key-words: Nanoemulsion; Photoprotection; Ethylhexyl methoxycinnamate; Benzophenone-3