NLC-Based Sunscreen Formulations with Optimized Proportion of Encapsulated and Free Filters Exhibit Enhanced UVA and UVB Photoprotection.

The topical use of sunscreens is recommended for avoiding the damaging effects of UV radiation. However, improvements are still needed in the existing products to enhance their photoprotection effectiveness and safety. This involves minimizing the use of chemical UV filters while providing enhanced and prolonged photoprotection. This work investigated novel sunscreen formulations and their UV protection effects by encapsulating Uvinul® A, Tinosorb® S, and Uvinul® T150 into nanostructured lipid carriers (NLCs) based on bacuri butter and raspberry seed oil. First, the impact of critical formulation and process parameters on NLCs' particle size was evaluated using a 22 Face Centered Central Composite Design. Then, formulations were evaluated in terms of critical quality factors, in vitro skin permeation, and in vitro and in vivo photoprotection activities. The developed NLCs-containing formulations exhibited appropriate size (122-135 nm), PdI (<0.3), encapsulation efficiency (>90%), and drug content (>80%), which were preserved for at least 90 days under different stability conditions. Moreover, these NLCs-based formulations had equivalent skin permeation to emulsion-based controls, and the addition of NLCs into sunscreen cream bases in the optimum proportion of 20% (w/w) resulted in enhanced UVA and UVB photoprotection levels, despite a 10% reduction in the total filters content. Altogether, these results describe the application of nanoencapsulated organic UV filters in innovative sunscreen formulations to achieve superior photoprotection and cosmeceutical properties.

Solid Lipid-Polymer Hybrid Nanoplatform for Topical Delivery of siRNA: In Vitro Biological Activity and Permeation Studies.

Small interfering RNA (siRNA) molecules have limited transfection efficiency and stability, necessitating the use of delivery systems to be effective in gene knockdown therapies. In this regard, lipid-polymeric nanocarriers have emerged as a promising class of nanoparticles for siRNA delivery, particularly for topical applications. We proposed the use of solid lipid-polymer hybrid nanoparticles (SLPHNs) as topical delivery systems for siRNA. This approach was evaluated by assessing the ability of SLPHNs-siRNA complexes to internalize siRNA molecules and both to penetrate skin layers in vitro and induce gene knocking down in a skin cell line. The SLPHNs were formed by a specific composition of solid lipids, a surfactant polymer as a dispersive agent, and a cationic polymer as a complexing agent for siRNA. The optimized nanocarriers exhibited a spherical shape with a smooth surface. The average diameter of the nanoparticles was found to be 200 nm, and the zeta potential was measured to be +20 mV. Furthermore, these nanocarriers demonstrated excellent stability when stored at 4 °C over a period of 90 days. In vitro and in vivo permeation studies showed that SLPHNs increased the cutaneous penetration of fluorescent-labeled siRNA, which reached deeper skin layers. Efficacy studies were conducted on keratinocytes and fibroblasts, showing that SLPHNs maintained cell viability and high cellular uptake. Furthermore, SLPHNs complexed with siRNA against Firefly luciferase (siLuc) reduced luciferase expression, proving the efficacy of this nanocarrier in providing adequate intracellular release of siRNA for silencing specific genes. Based on these results, the developed carriers are promising siRNA delivery systems for skin disease therapy.

TNFα siRNA delivery by nanoparticles and photochemical internalization for psoriasis topical therapy.

Psoriasis is a chronic inflammatory skin disease that presents increased expression of tumor necrosis factor α (TNFα), a proinflammatory cytokine. The discovery of RNA interference (RNAi), mediated by short interfering RNA (siRNA), made it possible for the expression of some genes to be eliminated. However, for its application, it is necessary to use carriers that can protect siRNA and release it in the target cells. Herein, we developed a delivery system for siRNA based on hybrid polymer-lipid nanoparticles (PLNs) and combined this system with photochemical internalization (PCI), photoactivating the photosensitizer TPPS2a, to optimize the endosomal escape of TNFα siRNA in the cytoplasm, aiming to use the system as a topical formulation to treat psoriasis. The PLNs composed of 2.0% of Compritol® 888 ATO (lipid), 1.5% of poloxamer 188 and 0.1% of the cationic polymer poly(allylamine hydrochloride) showed an average nanoparticle size of 142 nm, a zeta potential of +25 mV, and the ability to efficiently coencapsulate TPPS2a and complexed siRNA. In addition, these materials did not present cellular toxicity and showed high cellular uptake. In vitro delivery studies using porcine skin model revealed that the PLNs delivered siRNA and TPPS2a into the skin. The efficacy was verified using an in vivo psoriasis animal (hairless mouse) model induced by imiquimod (IMQ) cream. The results revealed that PLN-TPPS2a-TNFα siRNA combined with PCI resulted in a decrease in the levels of TNFα, showing the efficiency of the treatment to silence this cytokine in psoriatic lesions, which was accompanied by a reduction in the redness and scaling of the mouse skin. The results showed the potential of the developed PLNs in combined silencing gene therapy and PCI for topical treatment of psoriasis.

Development of nanoparticles from natural lipids for topical delivery of thymol: Investigation of its anti-inflammatory properties.

Wound healing involves the integration of biological and molecular events and, in case of chronic wounds, the use of drugs can be associated to side effects. Therefore, there is a search for alternatives therapeutics that encompass minimal toxicity. The use of natural compounds is an attractive approach for treating inflammatory disorders, wounds and burns. In this context, thymol has antimicrobial, antioxidant and antiseptic properties and is a promising compound in wound healing and inflammation management. However, essential oils and their constituents such as thymol present high volatility and can also easily decompose, thereby the encapsulation of these compounds into nanoparticles may be an efficient approach to modulate the release of the active ingredient, to increase the physical stability and to eventually reduce the toxicity. The aims of this work were to encapsulate thymol in nanostructured lipid carriers (NLCs) composed of natural lipids and assess its in vivo anti-inflammatory and antipsoriatic activity. The carrier containing thymol was produced by sonication method and showed 107.7 (±3.8) nm of size, zeta potential of -11.6 (±2.9) mV and entrapment efficiency of 89.1 (±4.2)%. Thymol-NLCs were incorporated into a gel and the final formulation presented rheological characteristics and pH suitable for topic application. In addition, the gel containing thymol-NLCs was tested in vivo on two different mouse models of skin inflammation, showing anti-inflammatory activity. Finally, this formulation was tested in an imiquimod-induced psoriasis mouse model and showed improved healing, compared to negative control. Therefore, thymol-NLCs is an interesting formulation for future treatment of inflammatory skin diseases.

Cognitive style and learning strategies as factors which affect academic achievement of brazilian university students / Estilo cognitivo e estratégias de aprendizagem em estudantes universitários brasileiros: repercussões no rendimento acadêmico

In the present study, the influence of the cognitive style called field dependence-independence on academic achievement of Brazilian university students was explored as well as the mediating effect of learning strategies on that influence. Learning strategies of 313 first-year university students (189 women and 124 men; M age = 20.86, SD = 3.86) from different fields, with upper, medium and lower scores on field dependence-independence were assessed on a self-report questionnaire and their overall academic marks in the first year were registered. Results of a regression analysis showed that cognitive style and learning strategies significantly contributed to academic achievement. A path analysis revealed that planning strategies mediated the influence of cognitive style on achievement.

No presente estudo, a influência do estilo cognitivo dependência-independência de campo no rendimento acadêmico de estudantes universitários brasileiros foi explorada, bem como o efeito mediador das estratégias de aprendizagem nesta influência. As estratégias de aprendizagem de 313 estudantes universitários de primeiro curso (189 mulheres e 124 homens, idade M=20,86, DP= 3,86) a partir de diferentes domínios, com pontuações elevadas, intermediárias e baixas em dependência-independência de campo, foram avaliadas em um auto questionário e as suas médias globais de rendimento acadêmico no primeiro ano foram registradas. Resultados de uma análise de regressão mostraram que o estilo cognitivo e as estratégias de aprendizagem contribuem significativamente para o sucesso acadêmico. Uma path analysis revelou que as estratégias de planejamento mediam a influência do estilo cognitivo na sua realização.

Cognitive style and learning strategies as factors which affect academic achievement of brazilian university students / Estilo cognitivo e estratégias de aprendizagem em estudantes universitários brasileiros: repercussões no rendimento acadêmico

In the present study, the influence of the cognitive style called field dependence-independence on academic achievement of Brazilian university students was explored as well as the mediating effect of learning strategies on that influence. Learning strategies of 313 first-year university students (189 women and 124 men; M age = 20.86, SD = 3.86) from different fields, with upper, medium and lower scores on field dependence-independence were assessed on a self-report questionnaire and their overall academic marks in the first year were registered. Results of a regression analysis showed that cognitive style and learning strategies significantly contributed to academic achievement. A path analysis revealed that planning strategies mediated the influence of cognitive style on achievement.(AU)

No presente estudo, a influência do estilo cognitivo dependência-independência de campo no rendimento acadêmico de estudantes universitários brasileiros foi explorada, bem como o efeito mediador das estratégias de aprendizagem nesta influência. As estratégias de aprendizagem de 313 estudantes universitários de primeiro curso (189 mulheres e 124 homens, idade M=20,86, DP= 3,86) a partir de diferentes domínios, com pontuações elevadas, intermediárias e baixas em dependência-independência de campo, foram avaliadas em um auto questionário e as suas médias globais de rendimento acadêmico no primeiro ano foram registradas. Resultados de uma análise de regressão mostraram que o estilo cognitivo e as estratégias de aprendizagem contribuem significativamente para o sucesso acadêmico. Uma path analysis revelou que as estratégias de planejamento mediam a influência do estilo cognitivo na sua realização.(AU)