Poly-ε-caprolactone based nanoparticles for delivery of genistein in melanoma treatment

Abstract We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studies.

Oral and nasal vaccination: current prospects, challenges, and impact of nanotechnology-based delivery systems

Abstract Currently, mucosal vaccine administration has stood out as an easier and non-invasive application method. It can also be used to induce local and systemic immune responses. In the COVID-19 pandemic context, nasal and oral vaccines have been developed based on different technological platforms. This review addressed relevant aspects of mucosal vaccine administration, with emphasis on oral and nasal vaccinations, in addition to the importance of using nanotechnology-based delivery systems to enable these strategies.

Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993) and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution) (p < 0.05) (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively). Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively). Further studies to evaluate skin sensitization and irritation are now necessary.

RESUMO Adesivos transdérmicos de nicotina são utilizados para cessação de fumar, tratamento de problemas de pele com infiltração de eosinófilos e para melhorar a atenção em pacientes com doença de Alzheimer e enfraquecimento da memória associada à idade. No entanto, a irritação da pele com o uso prolongado dos adesivos ainda é um problema. O objetivo deste trabalho foi desenvolver sistema líquido cristalino (SLC) de preparo simples contendo vitamina E TPGS capaz de controlar a liberação de nicotina e reduzir os problemas de irritação cutânea. Os SLCs foram caracterizados por análise visual e microscopia de luz polarizada. As administrações tópica e transdérmica de nicotina foram investigadas in vitro utilizando pele de orelha de porco em célula de difusão de Franz. A permeação da nicotina veiculada pela fase cúbica desenvolvida seguiu cinética de ordem zero (r = 0,993) e foi significativamente maior do que o controle (solução de nicotina) após 12 h (p < 0,05) (138,86 ± 20,44 e 64,91 ± 4,06 µg/cm2, respectivamente). A fase cúbica também promoveu aumento da penetração de nicotina nas camadas viáveis da pele quando comparado ao controle (8,18 ± 1,89 e 2,63 ± 2,51 µg/cm2, respectivamente). Estudos futuros para avaliar a sensibilização e irritação da pele são necessários.

Assessment of in vitro methodologies to determine topical and transdermal delivery of the flavonoid quercetin / Avaliação de metodologias in vitro para determinar a liberação tópica e transdérmica da quercetina

To be effective against the oxidative damages induced by UVB irradiation in the skin, the drug needs to release from the formulation in which it was incorporated and reach the skin layers where the ROS are generated. Thus, it is very important the development of a robust and sensitive methodology to extract and quantify in different skin layers the antioxidant agent delivered from topical formulations. Therefore, in the present work suitable methods to extract and quantify quercetin in skin samples and receptor phase after in vitro penetration studies were developed. The results demonstrated that the recovery from two different layers of skin, the SC and [E+D], using two different methods of quantification (DPPHò assay and HPLC, respectively), was 93.8 percent when the quercetin spiked dose was 50 µg/mL, 100.4 percent when it was 100 µg/mL and 89.9 percent for 250 µg/mL and the average recovery of the quercetin extraction from receptor phase when dichloromethane was used as extractor solvent was 96 percent. These results demonstrate that the described methods have a potential application to in vitro skin penetration studies of quercetin, since it showed to be accurate and sensitive.

Para ser efetiva contra os danos oxidativos induzidos pela radiação UVB na pele, é necessário que o ativo seja liberado da formulação na qual foi incorporado e alcance as camadas da pele onde são geradas as EROS. Desta forma, torna-se de grande importância o desenvolvimento de métodos eficazes e sensíveis para extrair e quantificar, nas diferentes camadas de pele, o agente antioxidante liberado de formulações tópicas. No presente trabalho foram desenvolvidos métodos adequados para extrair e quantificar a quercetina em amostras de pele e na fase receptora após estudos de penetração cutânea in vitro. Os resultados demonstraram que a recuperação das camadas de pele, EC e [E+D], quando do uso de duas diferentes metodologias de quantificação (ensaio de DPPHò e CLAE, respectivamente), foi de 93,8 por cento quando aplicada uma dose de 50 µg/mL de quercetina, 100,4 por cento para 100 µg/mL e 89,9 por cento para 250 µg/mL e a recuperação média da extração da quercetina da fase receptora, quando do emprego de diclorometano como solvente extrator, foi de 96 por cento. Tais resultados demonstram que os métodos descritos têm grande potencial de aplicação em estudos de penetração in vitro já que apresentaram exatidão e sensibilidade.