Effect of polycaprolactone nanocapsules loaded with essential oils on biofilm formation by Staphylococcus aureus strains isolated from bovine mastitis cases

Abstract Bovine infectious mastitis is largely resistant to antibacterial treatment, mainly due to mechanisms of bacterial resistance in the biofilms formed by Staphylococcus aureus. Melaleuca (MEO) and citronella essential oils (CEO) are promising agents for reducing or eliminating biofilms. Free melaleuca oil presented a medium Minimum Inhibitory Concentration (MIC) of 0.625% and a Minimum Bactericidal Concentration (MBC) of 1.250%, while free citronella oil showed medium MIC and MBC of 0.313%. Thus, free CEO and MEO demonstrate bacteriostatic and bactericidal potential. We generated polymeric nanocapsules containing MEO or CEO and evaluated their efficacy at reducing biofilms formed by S. aureus. Glass and polypropylene spheres were used as test surfaces. To compare the responses of free and encapsulated oils, strains were submitted to 10 different procedures, using free and nanoencapsulated essential oils (EOs) in vitro. We observed no biofilm reduction by MEO, free or nanoencapsulated. However, CEO nanocapsules reduced biofilm formation on glass (p=0.03) and showed a tendency to diminish biofilms on polypropylene (p=0.051). Despite nanoencapsulated CEO reducing biofilms in vitro, the formulation could be improved to modify the CEO component polarity and, including MEO, to obtain more interactions with surfaces and the biofilm matrix

Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model / Efeito Protetor de Nanopartículas Poliméricas com Indometacina contra Citotoxicidade Induzida por Estresse Oxidativo em Modelo Celular de Adenocarcinoma de Mama Humano / Efecto Protector de Nanopartículas Poliméricas con Indometacina contra la Citotoxicidad Inducida por Estrés Oxidativo en Modelo de Células de Adenocarcinoma de Mama Humano

Introduction: Anti-inflammatory drugs are being utilized to treat cancer because of its inflammatory microenvironment. Objective: The objective of this study is to investigate the antioxidant potential of indomethacin and its genotoxicity, since free or loaded in polymeric nanocapsules using MCF-7 (human breast cancer) cells as an in vitro model. Method: Development of indomethacin-loaded polyepsilon-caprolactone (PCL) nanocapsules by interfacial deposition method. It is characterized by pH determination by potentiometer, mean diameter and polydispersity index by dynamic light scattering; zeta potential by electrophoretic mobility; encapsulation efficacy by high performance liquid chromatography method; corona effect formation; 2',7'-dichlorofluorescin diacetate (DCFH-DA) method by spectrofluorimetric assay; nitric oxide (NO) determination by spectrophotometric and genotoxicity assay by plasmid DNA cleavage method. Results: The results showed a mild acidic pH (4.78 ± 0.10), sizes around 200 nm and PDI<0.2 with a zeta potential around -20 mV and encapsulation efficiency of 99% (1 mg mL-1), showing a dose-dependent corona formation profile in 24h incubation. Conclusion: DCFH-DA assay showed no production of reactive oxygen species (ROS) while NO determination showed that Ind-OH-NC from 26.7 to 100 µM increased reactive nitrogen species (RNS), demonstrating antioxidant potential against MCF-7 cells. No sample at the concentrations evaluated induced DNA cleavage, being considered a safe treatment

Introdução: Anti-inflamatórios estão sendo empregados para tratamento de câncer por causa do seu ambiente inflamado. Objetivo: Investigar o potencial antioxidante da indometacina e sua genotoxicidade, livre ou carreada em nanocápsulas poliméricas, usando como modelo in vitrocélulas MCF-7 (câncer de mama humano). Método: Desenvolvimento de nanocápsulas de poliepsilon-caprolactona (PCL) por método de deposição interfacial, caracterizada por determinação de pH por potenciômetro; diâmetro médio e índice de polidispersão por espalhamento dinâmico de luz; potencial zeta por mobilidade eletroforética; eficiência de encapsulação por cromatografia líquida de alta eficiência; formação de efeito corona; método de 2',7'-diclorofluoresceína diacetato (DCFH-DA) por ensaio espectrofluorimétrico; determinação de óxido nítrico (NO) por espectrometria e ensaio de genotoxicidade por método de clivagem do DNA plasmidial. Resultados: Os resultados mostraram leve pH ácido (4,78 ± 0,10), tamanhos em torno de 200 nm e PDI<0,2 com potencial zeta em torno de -20 mV e eficiência de encapsulação de 99% (1 mg mL-1), apresentando perfil de formação de corona dose-dependente em 24 horas de incubação. Conclusão: O ensaio DCFH-DA mostrou que não há produção de espécies reativas de oxigênio (ROS), enquanto a determinação de NO mostrou que Ind-OH-NC de 26,7 a 100 µM aumentou as espécies reativas de nitrogênio (RNS), demonstrando potencial antioxidante contra MCF-7. Nenhuma amostra nas concentrações avaliadas induziu clivagem do DNA, sendo considerado um tratamento seguro

Introducción: Se están utilizando antiinflamatorios para tratamiento de cáncer debido a su entorno inflamado. Objetivo: Investigar el potencial antioxidante de la indometacina y su genotoxicidad, libre o acarreada en nanocápsulas poliméricas utilizando como modelo in vitro células MCF-7 (cáncer de mama humano). Método: Desarrollo de nanocápsulas de poli epsilon-caprolactona (PCL) por método de deposición interfacial, caracterizada por determinación de pH por potenciómetro; diámetro medio e índice de polidispersión por esparcimiento dinámico de luz; potencial zeta por movilidad electroforética; eficiencia de encapsulación por cromatografía líquida de alta eficiencia; formación de efecto corona; método de 2',7'-diclorofluoresceína diacetato (DCFH-DA) por ensayo espectrofluorímetro; determinación de óxido nítrico (NO) por espectrometría y ensayo de genotoxicidad por método de clivaje del ADN plasmídico. Resultados: Los resultados mostraron ligero pH ácido (4,78 ± 0,10), tamaños alrededor de 200 nm y PDI<0,2 con potencial zeta alrededor de -20 mV y eficiencia de encapsulación de 99% (1 mg mL-1), presentando perfil de formación de corona dosis-dependiente en 24h de incubación. Conclusión: El ensayo DCFDA mostró que no hay producción de especies reactivas de oxígeno (ROS) mientras que la determinación de NO mostró que Ind-OH-NC de 26,7 a 100 µM aumentó las especies reactivas de nitrógeno (RNS), demostrando potencial antioxidante contra MCF-7. Ninguna muestra en las concentraciones evaluadas indujo clivaje del ADN, siendo considerado un tratamiento seguro

Protective Effect of Indomethacin-loaded Polymeric Nanoparticles Against Oxidative Stress-Induced Cytotoxicity in Human Breast Adenocarcinoma Cell Model / Efeito Protetor de Nanopartículas Poliméricas com Indometacina contra Citotoxicidade Induzida por Estresse Oxidativo em Modelo Celular de Adenocarcinoma de Mama Humano / Efecto Protector de Nanopartículas Poliméricas con Indometacina contra la Citotoxicidad Inducida por Estrés Oxidativo en Modelo de Células de Adenocarcinoma de Mama Humano

Anti-inflammatory drugs are being utilized to treat cancer because of its inflammatory microenvironment. Objective: The objective of this study is to investigate the antioxidant potential of indomethacin and its genotoxicity, since free or loaded in polymeric nanocapsules using MCF-7 (human breast cancer) cells as an in vitro model. Method: Development of indomethacin-loaded polyepsilon-caprolactone (PCL) nanocapsules by interfacial deposition method. It is characterized by pH determination by potentiometer, mean diameter and polydispersity index by dynamic light scattering; zeta potential by electrophoretic mobility; encapsulation efficacy by high performance liquid chromatography method; corona effect formation; 2',7'-dichlorofluorescin diacetate (DCFH-DA) method by spectrofluorimetric assay; nitric oxide (NO) determination by spectrophotometric and genotoxicity assay by plasmid DNA cleavage method. Results: The results showed a mild acidic pH (4.78 ± 0.10), sizes around 200 nm and PDI PDI<0.2 with a zeta potential around -20 mV and encapsulation efficiency of 99% (1 mg mL-1), showing a dose-dependent corona formation profile in 24h incubation. Conclusion: DCFH-DA assay showed no production of reactive oxygen species (ROS) while NO determination showed that Ind-OH-NC from 26.7 to 100 µM increased reactive nitrogen species (RNS), demonstrating antioxidant potential against MCF-7 cells. No sample at the concentrations evaluated induced DNA cleavage, being considered a safe treatment

Introdução: Anti-inflamatórios estão sendo empregados para tratamento de câncer por causa do seu ambiente inflamado. Objetivo: Investigar o potencial antioxidante da indometacina e sua genotoxicidade, livre ou carreada em nanocápsulas poliméricas, usando como modelo in vitro células MCF-7 (câncer de mama humano). Método: Desenvolvimento de nanocápsulas de poliepsilon-caprolactona (PCL) por método de deposição interfacial, caracterizada por determinação de pH por potenciômetro; diâmetro médio e índice de polidispersão por espalhamento dinâmico de luz; potencial zeta por mobilidade eletroforética; eficiência de encapsulação por cromatografia líquida de alta eficiência; formação de efeito corona; método de 2',7'-diclorofluoresceína diacetato (DCFH-DA) por ensaio espectrofluorimétrico; determinação de óxido nítrico (NO) por espectrometria e ensaio de genotoxicidade por método de clivagem do DNA plasmidial. Resultados: Os resultados mostraram leve pH ácido (4,78 ± 0,10), tamanhos em torno de 200 nm e PDI<0,2 com potencial zeta em torno de -20 mV e eficiência de encapsulação de 99% (1 mg mL-1), apresentando perfil de formação de corona dose-dependente em 24 horas de incubação. Conclusão: O ensaio DCFH-DA mostrou que não há produção de espécies reativas de oxigênio (ROS), enquanto a determinação de NO mostrou que Ind-OH-NC de 26,7 a 100 µM aumentou as espécies reativas de nitrogênio (RNS), demonstrando potencial antioxidante contra MCF-7. Nenhuma amostra nas concentrações avaliadas induziu clivagem do DNA, sendo considerado um tratamento seguro

Introducción: Se están utilizando antiinflamatorios para tratamiento de cáncer debido a su entorno inflamado. Objetivo: Investigar el potencial antioxidante de la indometacina y su genotoxicidad, libre o acarreada en nanocápsulas poliméricas utilizando como modelo in vitro células MCF7 (cáncer de mama humano). Método: Desarrollo de nanocápsulas de poli epsilon-caprolactona (PCL) por método de deposición interfacial, caracterizada por determinación de pH por potenciómetro; diámetro medio e índice de polidispersión por esparcimiento dinámico de luz; potencial zeta por movilidad electroforética; eficiencia de encapsulación por cromatografía líquida de alta eficiencia; formación de efecto corona; método de 2',7'-diclorofluoresceína diacetato (DCFH-DA) por ensayo espectrofluorímetro; determinación de óxido nítrico (NO) por espectrometría y ensayo de genotoxicidad por método de clivaje del ADN plasmídico. Resultados: Los resultados mostraron ligero pH ácido (4,78 ± 0,10), tamaños alrededor de 200 nm y PDI<0,2 con potencial zeta alrededor de -20 mV y eficiencia de encapsulación de 99% (1 mg mL-1), presentando perfil de formación de corona dosis-dependiente en 24h de incubación. Conclusión: El ensayo DCFDA mostró que no hay producción de especies reactivas de oxígeno (ROS) mientras que la determinación de NO mostró que Ind-OH-NC de 26,7 a 100 µM aumentó las especies reactivas de nitrógeno (RNS), demostrando potencial antioxidante contra MCF-7. Ninguna muestra en las concentraciones evaluadas indujo clivaje del ADN, siendo considerado un tratamiento seguro

Docosahexaenoic fatty acid nanoencapsulated with Anti-PECAM-1 as strategy to increase atherosclerotic plaque stability / Ácido graxo docosahexaenoico nanoencapsulado com anti-PECAM-1 como uma estratégia para aumentar a estabilidade de placas ateroscleróticas

Cardiovascular diseases (CVDs) are the main cause of mortality worldwide, being the ischemic heart disease responsible for 85% of deaths. Atherosclerosis is a chronic inflammation of the arteries that underlies ischemic forms of CVD and involves the innate and adaptive immune systems, from initial fatty streak formation to atherosclerotic plaque ruptures, which defines the beginning and end stages of disease, respectively. Recent research on the reduction of systemic inflammation in order to treat CVD is controversial, since results show that this reduced inflammation can also increase patient susceptibility to general infection. Therefore, new tissue-targeting strategies are necessary. Docosahexaenoic fatty acid (DHA) is a natural bioactive precursor of pro-resolving oxylipins that can reduce inflammation. Based on these factors, the objective of this study was to develop a nanocapsule containing algae oil as a DHA source and apply anti-PECAM-1 on its surface to drive it to the inflamed endothelium. Initially, a surface-functionalized metal-complex multi-wall nanocapsule containing algae oil in its nucleus (MLNC-DHA-a1) was developed. This nanocapsules presented a mean diameter of 163 ± 5 nm, was spherical in shape, showed 94.80% conjugation efficiency using 200 µg/mL of anti-PECAM-1 on the surface, and did not show significant toxicity toward HUVECs at concentrations from 0.14 to 2.90x1011 nanocapsules/mL. The nanocapsules were also stable for 2 h, sufficient time to allow for clinical applications. In cell viability assays, concentrations of 0.14 to 1.40x1011 nanocapsules/mL did not significantly affect the viability of immortalized murine macrophages (RAW 264.7) and U-937 cells after 24, 48, and 72 h of treatment. Finally, macrophages were incubated with 0.75x1011 MLNC-DHA-a1 nanocapsules/mL for 4 h and showed a significant uptake, observed using dark-field hyperspectral microscopy (CytoViva®). Once inside murine macrophages (RAW 264.7), MLNC-DHA-a1 nanocapsules promoted a strong increase in M2 phenotype polarization compared to non-treated control cells. Our results suggest that DHA-enriched algae oil, as part of a lipid core nanocapsules, does not reduce cell viability and improves macrophage phenotype, making it a promising potential therapy for controlling chronic inflammation and healing or stabilizing atherosclerotic plaques

As doenças cardiovasculares (DCVs) são a principal causa de mortalidade no mundo, sendo os eventos isquêmicos responsáveis por 85% das mortes. A aterosclerose é uma inflamação crônica das artérias associada aos eventos isquêmicos das DCVs, na qual o sistema imunológico inato e adaptativo estão envolvidos desde a formação inicial das estrias gordurosas até a ruptura das placas ateroscleróticas. Pesquisas recentes direcionadas à redução da inflamação sistêmica têm mostrado resultados controversos, pois essa abordagem pode aumentar a susceptibilidade do paciente a infecções. Nesse sentido, novas estratégias direcionadas ao tecido lesionado são necessárias. No que se refere a medicamentos anti-inflamatórios ou suplementos alimentares, o ácido docosaexaenóico (DHA) tem sido relatado como um precursor natural de oxilipinas pró- resolutivas. Baseado nesse contexto, o objetivo deste estudo foi desenvolver nanocápsulas contendo óleo de alga como fonte de DHA e vetorizar essas nanopartículas com o anticorpo antiPECAM-1 em sua superfície, visando direcioná-las ao endotélio inflamado. Inicialmente, a nanocápsula multiparede metal-complexa funcionalizada contendo óleo de alga em seu núcleo (MLNC-DHA-a1) foi desenvolvida, apresentando um diâmetro médio de 163 ± 5 nm, formato esférico, onde a eficiência de conjugação do anti-PECAM-1 (200 µg/mL) foi de 94,80% sem toxicidade significativa em HUVECs nas concentrações de 1.14 a 2.9 x 1011 nanocápsulas/mL. As nanocápsulas apresentaram uma estabilidade de 2h, o que representa tempo suficiente para a sua aplicação clínica. A seguir, ensaios de viabilidade celular foram realizados em outras linhagens de células para avaliar a toxicidade das nanocápsulas. As concentrações de 0.14 a 1.40 x 1011 de nanocápsulas/mL não afetaram significativamente a viabilidade celular de macrófagos murinos imortalizados (RAW 264.7) e U-937 após 24, 48 e 72 h de tratamento. Por fim, os macrófagos (RAW 264.7) foram incubados com 0.75 x 1011 MLNC-DHA-a1/mL durante 4 h e apresentam uma captação significativa das nanocápsulas, observada por microscopia hiperespectral de campo escuro (CytoViva®). Uma vez captadas pelos macrófagos murinos imortalizados (RAW 264.7), as nanoformulações MLNC-DHA-a1 promoveram um forte aumento da polarização do fenótipo M2 em comparação com as células controle não tratadas. Nossos resultados sugerem que o óleo de alga rico em DHA presente no núcleo lipídico das nanocápsulas, não reduziu a viabilidade celular e estimulou uma maior polarização de macrófagos para o tipo M2, sendo assim uma terapia potencial para controlar a inflamação crônica e cicatrizar ou estabilizar placas ateroscleróticas

Diphenyl Diselenide and Clotrimazole Co-loaded into Eudragit® RS 100 Nanocapsules Formulation Has Superior Antioxidant Potential and Promising Anti-candida Activity

Abstract In the current study, nanocapsules (NC) formulations containing a co-load of clotrimazole (C), a highly prescribed antifungal drug, and diphenyl diselenide [(PhSe)2], an organoselenium compound with a promising scope of pharmacological actions, were prepared. Formulations were characterized as well as the potential toxicity, antioxidant action, and antifungal effect were assessed using in vitro techniques. The NCs were prepared employing Eudragit® RS 100 as polymeric wall and medium chain triglycerides or virgin coconut oil (CO) as core. All NC suspensions had pH around acid range, compound content close to theoretical value (1 mg/mL/drug), average diameter in nanometric range, positive values of zeta potential as well as high encapsulation efficacy and mucoadhesive property. Physicochemical stability was performed over a 30-day period and showed no modification in the aforementioned parameters to all samples. Preliminary screening of toxicological potential performed by the hen's egg test chorioallantoic membrane technique classified the formulations as non-irritant. The DPPH radical assay revealed that nanoencapsulated compounds had superior antioxidant action in comparison to their free forms (concentration range tested 1.0-25.0 µg/mL). Importantly, the formulation composed of CO and containing C and (PhSe)2 showed the highest antioxidant potential and was selected for further investigation regarding antifungal effect against some Candida spp strains. Results of in vitro antifungal assay demonstrated that the C and (PhSe)2 co-encapsulation had a minimum inhibitory concentration (MIC) values around 60. Thus, our study supplies additional data about advantages achieved by encapsulating active compounds.

PEG-PCL Nanocapsules Containing Curcumin: Validation of HPLC Method for Analyzing Drug-loading Efficiency, Stability Testing and Cytotoxicity on NIH-3T3 Cell Line

Abstract Curcumin (CUR) shows potential use for treating cancer. However, CUR has low solubility and reduced bioavailability, which limit its clinical effect. Therefore, the development of nanocarriers can overcome these problems and can ensure the desired pharmacological effect. In addition, it is mandatory to prove the quality, the efficacy, and the safety for a novel nanomedicine to be approved. In that sense, this paper aimed (a) to prepare CUR-loaded polyethylene glycol-poly(ε-caprolactone) nanocapsules; (b) to validate an analytical method by high performance liquid chromatography (HPLC) for quantifying CUR in these nanoformulations; (c) to evaluate the physicochemical stability of these formulations; and to investigate their cytotoxicity on NIH-3T3 mouse fibroblast cells. The HPLC method was specific to CUR in the loaded nanocapsules, linear (r = 0.9994) in a range of 10.0 to 90.0 µg.mL-1 with limits of detection and quantification of 0.160 and 0.480 µg.mL-1, respectively. Precision was demonstrated by a relative standard deviation lower than 5%. Suitable accuracy (102.37 ± 0.92%) was obtained. Values of pH, particle size, polydispersity index, and zeta potential presented no statistical difference (p > 0.05) for CUR-loaded nanoparticles. No cytotoxicity was observed against NIH-3T3 mouse embryo fibroblast cell line using both the tetrazolium salt and sulforhodamine B assays. In conclusion, a simple and inexpensive HPLC method was validated for the CUR quantification in the suspensions of nanocapsules. The obtained polymeric nanocapsules containing CUR showed suitable results for all the performed assays and can be further investigated as a feasible novel approach for cancer treatment.

Effect of Cilostazol-Loaded PCL/PEG Nanocapsules on Abdominal Aortic Tunics and Lipid Profile of Wistar Rats

Abstract Cilostazol (CLZ) is a phosphodiesterase III inhibitor with antiplatelet and vasodilator properties. It has been recently verified that CLZ plays a significant role in the arteries by inhibiting the proliferation and growth of muscle cells, increasing the release of nitric oxide by the endothelium and promoting angiogenesis. Considering these promising effects, the use of nanocapsules may be an interesting strategy to optimize its pharmacokinetics and pharmacodynamics at the vascular level for preventing atherosclerosis. The aim of this study was to evaluate the effect of cilostazol-loaded nanocapsules in the abdominal aortic tunics and on the lipid profile of Wistar rats in order to investigate its potential role in the prevention of atherosclerosis. Thirty-two animals were divided into four groups of eight animals, with 30-day treatment. Group 1 received nanoencapsulated CLZ; Group 2, control nanocapsules with no drug; Group 3, propylene glycol and water; and Group 4, a solution of CLZ in propylene glycol and water. After 30 days, there was no statistically significant difference between the groups regarding the cellularity and thickness of the arterial tunics of the abdominal aorta. However, the group that received nanoencapsulated CLZ (Group 1) had an improvement in HDL-c and triglyceride values compared to unloaded nanocapsules (Group 2).

Anthelmintic activity of nanoencapsulated carvacryl acetate against gastrointestinal nematodes of sheep and its toxicity in rodents / Atividade anti-helmíntica do acetato de carvacrila nanoencapsulado sobre nematoides gastrintestinais de ovinos e toxicidade em roedores

Abstract The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.

Resumo O objetivo deste trabalho foi avaliar a eficácia do acetato de carvacrila (ACV) e do ACV nanoencapsulado (nACV) sobre nematóides gastrintestinais de ovinos. O ACV foi nanoencapsulado com quitosana/goma arábica e foi analisada a eficácia de nanoencapsulamento (EE), o rendimento, potencial zeta, morfologia das nanopartículas e cinética de liberação em pH 3 e 8. Foram avaliadas as toxicidades aguda e subcrônica em roedores e a redução da contagem de ovos nas fezes (RCOF) de ovinos. Os ovinos foram divididos em quatro grupos (n = 10): G1, 250 mg/kg ACV; G2, 250 mg/kg de nACV; G3, matriz polimérica e G4: 2,5 mg/kg de monepantel. A EE e o rendimento de nACV foram de 65% e 57%, respectivamente. A morfologia das nanopartículas foi esférica, tamanho (810,6±286,7 nm), potencial zeta no pH 3,2 (+18,3 mV) e a liberação de 50% de CVA nos pHs 3 e 8 ocorreu às 200 e 10 h, respectivamente. nACV apresentou DL50 de 2.609 mg/kg. ACV, nACV e o monepantel reduziram a contagem de ovos por grama de fezes (opg) em 57,7%, 51,1% e 97,7%, respectivamente. A contagem de opg de ovelhas tratadas com ACV e nCVA não diferiu do controle negativo (P>0,05). O nanoencapsulamento reduziu a toxicidade do AVC; no entanto, nACV e ACV apresentaram resultados semelhantes na RCOF.

Development and Characterization of Poly-ε -caprolactone Nanocapsules Containing β -carotene Using the Nanoprecipitation Method and Optimized by Response Surface Methodology

Abstract Nanoparticles demonstrate an important role in the protection of bioactive compounds from external factors such as temperature, oxygen and light. In this study, poly-ε-caprolactone (PCL) nanoparticles entrapped β-carotene was produced using the nanoprecipitation method. Firstly, was evaluated the lipophilic surfactant effect and carrier agent of the active compound in the nanocapsules formulation. After choosing the most stable formulation, the nanocapsules production was optimized using β-carotene, caprylic/capric triglycerides (CCT) and soybean lecithin. Response surface methodology (RSM) was adopted to evaluate the influence of soy lecithin concentration, volume of CCT and β-carotene concentration in the particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency and recovery. Formulations containing soy lecithin and CCT demonstrated better stability comparing to the other formulations tested. The nanoparticle formulations presented an optimized particle size below 200 nm, PDI lower than 0.1 and encapsulation efficiency above 95%. Based on the results obtained, the optimum conditions to prepare PCL nanocapsules were 0.2160 mg/mL of β-carotene, 232.42 μL of CCT and 2.59 mg/mL of soy lecithin, suggesting an applicability to promote controlled released of β-carotene in food system.

Desenvolvimento e caracterização de nanocápsulas poliméricas contendo carvacrol para inibição de Salmonella enteritidis / Development and characterization of polymeric nanocapsules containing carvacrol for inhibition from Salmonella enteritidis

Avaliou-se caracterização físico-química, ação bactericida e estabilidade de nanocápsulas poliméricas de Eudragit contendo carvacrol preparadas utilizando técnica de deposição interfacial do polímero pré-formado. As nanocápsulas apresentaram diâmetro médio de 146 nm, PDI de 0,181 e potencial zeta de + 23,44 mV e a concentração bactericida mínima necessária para inativar Salmonella Enteritidis foi de 0,331 mg/mL. A solução contendo nanocápsulas manteve suas características físico-químicas e atividade bactericida inalteradas durante os 45 dias do teste de estabilidade, demonstrando características promissoras para o desenvolvimento de um sanitizantes para uso em indústria produtora de ovos e frigorífico de aves.

Study on influence of polymer and surfactant on in vitro performance of biodegradable aqueous-core nanocapsules of tenofovirdisoproxil fumarate by response surface methodology

The major objective of this study was to investigate the effect of biodegradable polymer type and surfactant concentration on various characteristics viz. particle size, entrapment efficiency and drug release rate constant of aqueous core nanocapsules (ACNs) containing tenofovirdisoproxil fumarate. In this study, the nanocapsules were prepared by modified multiple emulsion technique with biodegradable polymers viz. poly(lactide-co-glycolide) of two different grades (PLGA RG502H and PLGA RG503H) and poly lactic acid (PLA R203H); and the surfactant employed was span 80. The experiments were designed under response surface methodology by employing the Design Expert software. Entrapment efficiency, particle size and drug release rate constant were taken as response variables. The prepared nanocapsules were subjected to characterization studies and the obtained results were statistically analyzed by Analysis of Variance (ANOVA) for response surface 2-Factorial Interaction model. ANOVA studies showed that the influence of both factors on all the response variables were significant at p<0.05. The optimized formulation was found to have the entrapment efficiency of 71.58%, particle size of 252.41 nm and the drug release rate constant of 0.045 h-1; thus, indicating that the ACNs were obtained with finest characteristics. SEM studies showed that the particles were spherical.

Nanoparticulate drug delivery systems for the treatment of neglected tropical protozoan diseases

Neglected Tropical Diseases (NTDs) comprise of a group of seventeen infectious conditions endemic in many developing countries. Among these diseases are three of protozoan origin, namely leishmaniasis, Chagas disease, and African trypanosomiasis, caused by the parasites Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei respectively. These diseases have their own unique challenges which are associated with the development of effective prevention and treatment methods. Collectively, these parasitic diseases cause more deaths worldwide than all other NTDs combined. Moreover, many current therapies for these diseases are limited in their efficacy, possessing harmful or potentially fatal side effects at therapeutic doses. It is therefore imperative that new treatment strategies for these parasitic diseases are developed. Nanoparticulate drug delivery systems have emerged as a promising area of research in the therapy and prevention of NTDs. These delivery systems provide novel mechanisms for targeted drug delivery within the host, maximizing therapeutic effects while minimizing systemic side effects. Currently approved drugs may also be repackaged using these delivery systems, allowing for their potential use in NTDs of protozoan origin. Current research on these novel delivery systems has provided insight into possible indications, with evidence demonstrating their improved ability to specifically target pathogens, penetrate barriers within the host, and reduce toxicity with lower dose regimens. In this review, we will examine current research on these delivery systems, focusing on applications in the treatment of leishmaniasis, Chagas disease, and African trypanosomiasis. Nanoparticulate systems present a unique therapeutic alternative through the repositioning of existing medications and directed drug delivery.(AU)

Sistemas de nanopartículas poliméricas II: estructura, métodos de elaboración, características, propiedades, biofuncionalización y tecnologías de auto-ensamblaje capa por capa (layer-by-layer self-assembly) / Polymeric nanoparticle systems: structure, elaboration methods, characteristics, properties, biofunctionalization and self-assembly layer by layer technologies

Los materiales poliméricos han sido ampliamente investigados para aplicaciones biomédicas, teniendo especial relevancia cuando se encuentran en forma de micro- y nano-partículas. Últimamente se ha ampliado su campo de aplicación al ser conjugados con péptidos y ácidos nucleicos, por lo tanto, el interés en el estudio de este tipo de materiales, así como también en la formulación de nanoestructuras funcionalizadas como materiales, dispositivos y vehículos de transporte de agentes terapéuticos ha aumentado. Las recientes investigaciones en nanosistemas se inspiran en fenómenos naturales que estimulan la integración de señales moleculares y la mimetización de procesos a nivel celular, de tejidos y órganos. Tecnológicamente, la capacidad de obtener nanoestructuras esféricas mediante la combinación de materiales que presenten propiedades distintas a las que ningún otro material individual posee por sí solo, es lo que hace que las nanocápsulas sean particularmente atractivas. Las potenciales ventajas de los sistemas de nanopartículas de tipo polimérico se destacan a lo largo de cada parte de este artículo de revisión. El presente artículo aborda los aspectos más relevantes sobre la estructura, composición y algunos métodos de elaboración de los sistemas nanoparticulados. Además, expone algunos de los trabajos más recientes, centrados en sistemas de nanopartículas basados en polímeros dirigidos a la administración de agentes, publicados en artículos especializados de investigación y revisiones durante los últimos años.

Polymeric materials have been extensively investigated for biomedical applications including micro- and nanoparticles. Modern advances have broadened horizons for application with peptides and nucleic acids. Therefore, interests increased in the formulation of materials, devices and vehicles for transporting therapeutic agents in functionalized nanostructures. Recent nano-systems are inspired by natural phenomena that stimulate the integration of molecular signals and the mimicking of natural cellular processes, at tissue and organ levels. Technologically, the ability to obtain spherical nanostructures, which combine different properties, that no other single material possesses on its own, makes nanocapsules particularly attractive. Potential advantages over polymer nanoparticulate systems are highlighted throughout each part of this review article. Here, we address the most relevant aspects of structure, composition and methods of formulation of nanoparticulate systems. In addition, we outline some of the more recent works focusing on nanosized preparations, based on agent-directed polymers, found in specialized research articles that have emerged in the recent years.

Retinal changes in rabbit after intravitreal injection of sunitinib encapsulated into solid lipid nanoparticles and polymeric nanocapsules / Avaliação das alterações retinais no coelho após injeção intravítrea de sunitinib encapsulado em nanoparticulas lípidas sólidas e nanocapsulas polímeros

ABSTRACT Purpose: We aimed to evaluate the safety of single intravitreal injection of each of two concentrations of 0.1 ml of sunitinib (1 and 10 mg/ml), 0.1 ml of a drug-free dispersion containing solid lipid nanoparticles, and 0.1 ml of a drug-free dispersion containing polymeric nanocapsules for analyzing the possible toxic effects using electrophysiology and histology in albino rabbit retina. Methods: We conducted an experimental controlled study of 20 eyes of albino rabbits. Intravitreal injections of each specific agent were applied to one eye per rabbit in each 5-rabbit group, while the contralateral eyes received no treatment and were used as controls. Results: We noted no electroretinographic changes in the sunitinib (1 and 10 mg/ml) or in solid lipid nanoparticles groups. However, we observed significant abnormalities in ocular morphology and in the electroretinogram in the nanocapsules group. At the histological level, only the nanocapsules group demonstrated abnormal changes, including severe edema and cytoplasmic vacuole formation. Conclusions: While nanocapsules intravitreal injections indicated retinal toxic effects, sunitinib and solid lipid nanoparticles intravitreal injections were not toxic to the retina. Our results suggest that a sunitinib preparation with solid lipid nanoparticles for controlled release may offer a significant therapeutic approach for vasoproliferative ocular disease.

RESUMO Objetivos: O presente estudo teve por objetivo avaliar a segurança da injeção intravítrea de 0,1 ml de sunitinibe em duas concentrações (1 mg/ml e 10 mg/ml), 0,1 ml de dispersão contendo nanopartículas lipídicas sólidas sem droga e 0,1 ml de dispersão contendo nanocápsulas poliméricas livre de drogas analisando os possíveis efeitos tóxicos à retina de coelhos albinos detectados pela eletrofisiologia e histologia por microscopia óptica. Métodos: Um estudo controlado experimental foi rea­lizado com 20 olhos de coelhos albinos. Foram realizadas injeções intravítrea de duas concentrações diferentes de suniti­nibe, uma dispersão contendo nanopartículas lipídicas sólidas e uma dispersão contendo nanocápsulas. O olho contralateral não recebeu tratamento e foi utilizado como controle. Resultados: Não foram observadas alterações eletrorretinográficas nos grupos do sunitinibe (1 mg/ml e 10 mg/ml) e no grupo das nanopartículas lipídicas sólidas. No grupo das nanocápsulas, houve alterações significativas tanto na morfologia, quanto na amplitude e tempo das ondas do eletrorretinograma. Ao estudo histológico, somente o grupo das nanocápsulas apresentou al­terações degenerativas (núcleos tumefeitos) com acentuado edema e formação de vacúolos citoplasmáticos, sugerindo toxidade retiniana. Conclusões: As injeções intravítreas de sunitinibe e nanopartículas lipídicas sólidas não foram tóxicas para a retina. No entanto, nanocápsulas mostraram ser tóxicas para a retina. Sendo assim, a possibilidade de poder combinar o potencial de uma droga que possui a capacidade de inibir duas importantes vias da angiogênese, às vantagens de liberação controlada das nanopartículas lipídicas sólidas, pode ser um importante recurso terapêutico para doenças vasoproliferativas oculares.

Effect on adhesion of a nanocapsules-loaded adhesive system

Abstract This study aimed to evaluate the in situ degree of conversion, contact angle, and immediate and long-term bond strengths of a commercial primer and an experimental adhesive containing indomethacin- and triclosan-loaded nanocapsules (NCs). The indomethacin- and triclosan-loaded NCs, which promote anti-inflammatory and antibacterial effects through controlled release, were incorporated into the primer at a concentration of 2% and in the adhesive at concentrations of 1, 2, 5, and 10%. The in situ degree of conversion (DC, n=3) was evaluated by micro-Raman spectroscopy. The contact angle of the primer and adhesive on the dentin surface (n = 3) was determined by an optical tensiometer. For the microtensile bond strength µTBS test (12 teeth per group), stick-shaped specimens were tested under tensile stress immediately after preparation and after storage in water for 1 year. The data were analyzed using two-way ANOVA, three-way ANOVA and Tukey's post hoc tests with α=0.05. The use of the NC-loaded adhesive resulted in a higher in situ degree of conversion. The DC values varied from 75.07 ± 8.83% to 96.18 ± 0.87%. The use of NCs in only the adhesive up to a concentration of 5% had no influence on the bond strength. The contact angle of the primer remained the same with and without NCs. The use of both the primer and adhesive with NCs (for all concentrations) resulted in a higher contact angle of the adhesive. The longitudinal μTBS was inversely proportional to the concentration of NCs in the adhesive system, exhibiting decreasing values for the groups with primer containing NCs and adhesives with increasing concentrations of NCs. Adhesives containing up to 5% of nanocapsules and primer with no NCs maintained the in situ degree of conversion, contact angle, and immediate and long-term bond strengths. Therefore, the NC-loaded adhesive can be an alternative method for combining the bond performance and therapeutic effects. The use of an adhesive with up to 5% nanocapsules containing indomethacin and triclosan and a primer with no nanocapsules maintained the long-term bond performance.

Chitosan and carboxymethylated derivative nanoparticles as delivery systems for biological products: preparation, characterization, stability and in vitro/in vivo evaluation / Nanopartículas de quitosana e derivado carboximetilado como sistemas de fornecimento (delivery) de produtos biológicos: preparo, caracterização, estabilidade e avaliação in vitro/in vivo

Chitosan is a biocompatible and biodegradable mucoadhesive polymer with unique advantages, such as the distinct trait of opening the junctions to allow paracellular transport of antigen and good tolerability. However, the poor solubility of chitosan in neutral or alkalinized media has restricted its applications in the pharmaceutical field. Chitosan can be easily carboxymethylated to improve its solubility in aqueous media, while its biodegradability and biocompatibility are preserved. Apart from this, carboxymethyl chitosan (CMCS) can be easily processed into nanoparticles which highlight its suitability and extensive usage for preparing different drug delivery formulations. The present study deals with the development and characterization of a delivery system based on CMCS nanoparticles using ovalbumin as model protein. We demonstrated that ovalbumin loaded nanoparticles were successfully synthetized using calcium chloride as a cross-linker by ionic gelation. The nanoparticles exhibited an average size of approximately 169 nm and presented a pseudo-spherical shape. The nanoparticles size increased according to the addition of CaCl2 due to the strong electrostatic attraction. During storage the nanoparticles size increased was attributed to swelling and aggregation. The loading efficiency of ovalbumin was found to be 17%. Confocal microscopy clearly showed the association between ovalbumin and CMCS chains into nanoparticles. Therefore, we suggest these nanoparticles can be considered as an attractive and promising carrier candidate for proteins and antigens. The major challenge that limits the use of such carriers is their instability in an aqueous medium. Thus, the next step of this work was to determine the robustness of several formulations using distinct freeze-drying protocols. This study demonstrated that mannitol in concentration of 10% (w/v) is well suited to preserve ovalbumin loaded CMCS nanocapsules from aggregation during lyophilization and subsequent reconstitution. Importantly, the results showed that an annealing step has a huge impact on porosity of freeze-dried cake by nearly complete crystallization of mannitol, once the crystalline matrix prevents the partial collapse and the formation of larger pores observed without annealing. Therefore, the usual observation that annealing increases the pore size due to growth of ice crystal size does not always apply, at least when crystallization of solute is involved. Since all characterizations and stability studies had been performed, the main purpose of this study was to develop a stable antigen delivery system for oral immunization using CMCS and inactivated rabies virus (RV) as the antigen. RV loaded nanoparticles was found to enhance both systemic (IgG) and local (IgA) immune responses against RV after oral delivery in mice. The effective doses 50% were 50-times higher than the negative controls, indicating that the immune response started only after the third boosting dose. Furthermore, enough neutralizing antibodies was produced to be protected against the harmful effects of the rabies virus. It is therefore concluded, that the CMCS nanoparticles formulated in this study, are suitable for oral vaccine delivery, and can be suggested as a promising delivery system for a diverse range of antigens as well as a gene/protein delivery system, especially for those positively charged. Since several approaches show that effective intervention in airway allergic inflammation can be achieved with allergen-activated interleukin-10-secreting cells, the final part of this work was dedicated to assessing whether IL-10 loaded chitosan nanoparticles (IL10-CSNPs) could be used as a possible inhalable therapeutic tool for preventing exacerbations in asthmatic patients. As positive controls, we also assess whether interleukin 17A and interleukin 9 have the ability to stimulate human airway smooth muscle (HASM) cell contractility using magnetic twisting cytometry (MTC). Significant decreased baseline cell stiffness was observed in HASM cells pre-treated with IL-10, but not with IL10-CSNPs, whereas treatment with IL-17A significantly enhanced baseline cell stiffening. Our findings reveal a previously unknown mechanism underlying immunotherapy for prevention and treatment of asthma

A quitosana é um polímero mucoadesivo biocompatível e biodegradável, com vantagens únicas, tais como a característica distinta de abrir as junções que permitim o transporte paracelular de antígenos e boa tolerabilidade. No entanto, sua baixa solubilidade em meios neutros ou alcalinizados tem restringido suas aplicações no campo farmacêutico. A quitosana pode ser facilmente carboximetilada para melhorar de sua solubilidade em meios aquosos, enquanto sua biodegradabilidade e biocompatibilidade são preservadas. Além disso, a carboximetilquitosana (CMCS) pode ser facilmente processada na forma de nanopartículas, o que destaca sua adequabilidade para uso extensivo no preparo de sistemas de delivery de medicamentos. O presente estudo trata do desenvolvimento e caracterização de um sistema de delivery baseado em nanopartículas de CMCS utilizando ovalbumina como proteína modelo. Nós demonstramos que as nanopartículas carregadas com ovalbumina foram sintetizadas com sucesso utilizando cloreto de cálcio como agente de reticulação por gelificação iônica. As nanopartículas exibiram um tamanho médio de aproximadamente 169 nm e apresentaram uma forma pseudo-esférica. O tamanho das nanopartículas aumentou de acordo com a adição de CaCl2 devido à forte atração eletrostática. Durante o armazenamento, o tamanho aumentado das nanopartículas foi atribuído a incorporação de água e agregação. A eficiência de encapsulamento da ovalbumina foi de aproximadamente 17%. A microscopia confocal mostrou claramente a associação entre ovalbumina e a cadeias de CMCS nas nanopartículas. Sugerimos, portanto, que tal sistema pode ser considerado como candidato atraente e promissor para o carreamento de proteínas e antígenos. O principal desafio que limita o uso desses carreadores consiste na instabilidade em meio aquoso. Assim, o próximo passo deste trabalho foi determinar a robustez de várias formulações utilizandose diferentes protocolos de liofilização. Este estudo demonstrou que o manitol em uma concentração de 10% (p/v) é adequado para preservar da agregação as nanocápsulas de CMCS carregadas com ovalbumina durante a liofilização e subsequente reconstituição. Mais importante, os resultados mostraram que uma etapa de annealing tem um enorme impacto sobre a porosidade da amostra liofilizada devido a quase completa cristalização do manitol, uma vez que a matriz cristalina evita o colapso parcial e a formação de poros maiores observados na ausência do annealing. Portanto, a observação comum de que o annealing aumenta o tamanho doporos devido ao crescimento dos cristais de gelo nem sempre se aplica, pelo menos quando a cristalização de um soluto está envolvida. Uma vez que todas as caracterizações e estudos de estabilidade foram realizados, o principal objetivo deste estudo foi desenvolver um sistema estável de delivery de antígeno para imunização oral utilizando CMCS e vírus rábico inativado (RV) como antígeno. Verificou-se que as nanopartículas carregadas com RV aumentam as respostas imune sistêmica (IgG) e local (IgA) contra o RV após administração oral em camundongos. As doses efetivas 50% foram 50 vezes maiores que os controles negativos, indicando que a resposta imune foi iniciada apenas após a terceira dose da vacina. Além disso, foram produzidos anticorpos neutralizantes suficientes para proteção contra os efeitos nocivos do vírus rábico. Conclui-se, portanto, que as nanopartículas de CMCS formuladas neste estudo, são adequadas para o delivery oral de vacinas, e podem ser sugeridas como um sistema promissor de delivery para uma gama diversa de antígenos, bem como para o delivery de genes/proteínas, especialmente para aqueles carregados positivamente. Uma vez que diversas abordagens mostram que uma intervenção efetiva em casos de inflamação alérgica de vias aéreas pode ser conseguida por meio de células secretoras de interleucina 10 (IL-10) mediante ativação por alergenos, a parte final deste trabalho esteve dedicada a avaliação de nanopartículas de quitosana carregadas com IL-10 (IL10-CSNPs) como possível ferramenta terapêutica inalável para prevenção de exacerbações em pacientes asmáticos. Como controles positivos, avaliou-se adicionalmente se as interleucinas 17A (IL-17A) e 9 (IL-9) possuem a capacidade de estimular a contratilidade de células humanas de músculo liso de vias aéreas humanas (HASM) por meio de citometria de torção magnética (MTC). Uma diminuição significativa da rigidez celular basal foi observada em células HASM pré-tratadas com IL-10, mas não com IL10-CSNPs, enquanto que o tratamento com IL-17A aumentou significativamente a magnitude rigidez celular basal. Nossos resultados revelam um mecanismo previamente desconhecido subjacente à imunoterapia para prevenção e tratamento da asma

Preparation of mupirocin-loaded polymeric nanocapsules using essential oil of rosemary

Abstract The purpose of this study was to prepare and characterize mupirocin-loaded polymeric nanocapsules using two different oils and to develop and validate an analytical method for quantitative determination by high performance liquid chromatography. The mean size of the nanoparticles was 233.05 nm and 275.03 nm for nanocapsules with a rosemary oil like oily core and caprylic/capric triglyceride, respectively, and a good polydispersity index below 0.25 for both formulations. The nanocapsules showed good stability when stored at 40 ºC and room temperature for 30 days. The quantitative method was performed with a mobile phase consisting of ammonium ammonium acetate (0.05 M adjusted to pH 5.0 with acetic acid) and acetonitrile 60:40 (v/v); the flow rate was 0.8 mL/min, UV detection at 230 nm. The analytical method was linear in the range of 5.0-15.0 µg/mL, specific for both oils, accurate, precise (intermediate precision RSD = 1.68% and repeatability RSD = 0.81%) and robust under the evaluated conditions. Therefore, this method can be performed for quantification of mupirocin in polymeric nanocapsules containing both oils.

Pullulan as a stabilizer agent of polymeric nanocapsules for drug delivery

ABSTRACT Polymeric stabilizers have received attention in the preparation of nanostructured systems due to their ability to enhance formulation stability. Considering this, the objective of this work was to prepare poly(ε-caprolactone) nanocapsules using the pullulan as a polymeric stabilizer. The nanocapsules were prepared using the interfacial deposition method of preformed polymers and they were characterized in terms of pH, average diameter, polydispersity index, zeta potential, beclomethasone dipropionate content, encapsulation efficiency, photostability and drug release profiles. The formulations showed physicochemical characteristics consistent with nanocarriers for drug delivery such as: average diameter lower than 270 nm, polydispersity indexes lower than 0.2, negative zeta potential (-22.7 to -26.3 mV) and encapsulation efficiencies close to 100%. In addition, the nanocapsules were able to delay the beclomethasone dipropionate photodegradation under UVC radiation and by the dialysis bag diffusion technique, the nanocapsules were able to prolong the drug release. Thus, pullulan could be considered an interesting excipient to formulate polymeric nanocapsules.

Caracterização farmacêutica de nanocápsulas de timol e avaliação da permeação cutânea e da atividade repelente contra Aedes aegypti

A dengue é uma doença infecciosa que pode se manifestar de forma grave, com quadros hemorrágicos. O agente etiológico é um arbovirus transmitido pela picada do mosquito Aedes aegypti, principal vetor da doença. As principais medidas de combate são controle do mosquito e proteção individual, que pode dar-se com o uso de repelentes. Quase a totalidade dos repelentes no mercado possui DEET como ativo, que possui restrições de uso. Nestes entido, o timol (monoterpeno) tem-se mostrado promissor como repelente de inseto (Ae.aegypti), sendo a agregação de tecnologias essencial para a viabilidade de um produto repelente à base de timol. Diante do exposto, o objetivo do presente trabalho foi a preparação e caracterização farmacêutica de nanocápsulas de timol, com avaliação da permeação cutânea, citotoxicidade e atividade repelente de inseto (Ae. aegypti). Para tanto, foi desenvolvido evalidado método analítico para identificação e quantificação do timol por CLAE-DAD nas nanocápsulas de timol (NCT – 1%), que apresentou um teor de ativo em torno de 85%.Prosseguindo a caracterização das NCT, foram determinados o diâmetro médio, índice depolidispersão (PDI), potencial zeta (PZ), eficiência de encapsulação e pH, além do estudo de estabilidade. Análises das NCT mostraram um diâmetro médio de aproximadamente 150 nm,PZ negativo (-27,83 ± 2,60), PDI abaixo de 0,2 e uma eficiência de encapsulação de 98 %...

Dengue is an infectious disease that may also happen in a severe form with hemorrhagicevents. The etiological agent of the disease is an arbovirus wich is transmitted by themosquito Aedes aegypti, the primary vector of the disease. The main actions to combat thedisease are mosquito control and personal protection that can take place using repellents.Almost all repellents have DEET as active substance, which has use restrictions. In thiscontext, thymol (monoterpene) has become a potential insect repellent against Ae. aegypti,and the use of technologies is essential to the viability of a repellent thymol based product.Given the above, the aim of this study was the preparation and pharmaceuticalcharacterization of thymol nanocapsules and evaluation of skin permeation, in vitrocytotoxicity and mosquito repellence (Ae. aegypti). For this purpose, we developed andvalidated analytical method for identification and quantification of thymol by HPLC-PDA.Nanocapsules thymol (NCT - 1%) showed an active content of 85%. Continuing thecharacterization, NCT were analyzed for the mean diameter (D), polydispersity index (PDI),potential zeta (PZ), encapsulation efficiency, pH and product stability . Results shared showedan average diameter of approximately 150 nm, negative PZ (-27,83 ± 2,60), PDI less than 0.2and an encapsulation efficiency of 98%...