Triterpenes and antitubercular activity of Byrsonima crassa

We evaluated the potential antitubercular activity of triterpenes obtained from leaves and bark of Byrsonima crassa. From chloroform extracts of the leaves, by bioassay-guided fractionation, we obtained mixtures of known triterpenes: α-amyrin, β-amyrin and their acetates, lupeol, oleanolic acid, ursolic acid and α-amyrinone. Tested against Mycobacterium tuberculosis, the triterpenes exhibited minimum inhibitory concentrations (MICs) of 31.25 - 312.25 µg/mL. β-amyrin and friedelin, isolated from the chloroform extract of bark, showed MICs of 312.25 and 125 µg/mL respectively. This is the first report of the identification and determination of the activity of B. crassa triterpenes against M. tuberculosis

Development of a Nanotechnology Matrix-Based Citronella Oil Insect Repellent to Obtain a Prolonged Effect and Evaluation of the Safety and Efficacy

Mosquito-borne diseases affect millions of people worldwide each year, and the use of a topically applied insect repellent is an economically viable preventative health practice. The general objective of this work was to encapsulate citronella oil (CO) in a nanostructured lipid carrier (NLC) to formulate a topical repellent with a long duration of efficacy on the skin and a good safety profile based on minimizing skin penetration. In the studied CO, the main chemical constituents of geraniol, citronellal, and citronellol were identified and subsequently used as markers for the in vitro skin permeation testing (IVPT). An optimal NLC encapsulating CO formulation was developed and had an average particle size of 350 nm. The NLC was then formulated in combination with CO at ratios of 2:1, 1:1, and 1:2 CO:NLC-CO as oil-in-water (O/W) emulsions and compared to CO in the same O/W emulsion base (all at 10% CO in the final O/W topical formulation). The markers geraniol, citronellol, and citronellal were detected in all samples tested F1 (10% CO in O/W emulsion) and F3 (10% CO/NLC-CO 1:1 in O/W emulsion). Even the percentages of F3 markers were higher than F1. The recovery of the percentage balance (based on the total remaining on the skin surface, on the skin, and penetrated through the skin to the receptor) of geraniol, citronellol, and citronellal markers for F1 and F3 was 7.70% and 11.96%; 25.51% and 31.89%; and 5.09% and 4.40%, respectively. The nanoparticle lipid solid forms a repellent reservoir on the skin surface, releasing the active ingredients slowly through volatilization, extending the repellent action, and reducing permeation through the skin. It is possible to assume that the remaining 92.30% and 88.03%; 74.49% and 68.11%; and 94.10% and 95.60% of geraniol, citronellol, and citronellal markers of F1 and F3, respectively, were lost to evaporation. In the in vivo efficacy test carried out with the Aedes aegypti mosquito, F3 was the optimal formulation, providing the greatest repellent action compared to free oil in O/W emulsion. Thermal analysis showed that the NLC-CO raised the boiling point of the encapsulated CO compared to the free oil, suggesting that the controlled release of the CO was a possible mechanism for its prolonged effect. We concluded that the nanocarriers developed with CO were stable and provided improved mosquito-repellent efficacy with minimal skin penetration of the CO actives over 24 h. Indeed, regardless of whether the CO was applied as free oil, a 1:1 mixture of CO (pure/free oil) or NLC-CO applied in an O/W emulsion can be considered safe for topical application due to minimal skin penetration

Desenvolvimento de repelente com óleo de citronela em matriz nanotecnológica e sua avaliação de segurança e eficácia

Doenças transmitidas por mosquitos afetam milhões de pessoas no mundo a cada ano e o uso de repelente é uma prática economicamente viável para se prevenir. Sendo assim, propor alternativas mais seguras, efeitos mais duradouros e eficazes contra diversos insetos é bastante recomendável. Os repelentes naturais tem demonstrado bons resultados quanto sua eficácia e segurança como, por exemplo o óleo de citronela. O objetivo geral deste trabalho foi encapsular o óleo de citronela em carreador lipídico nanoestruturado (CLN) para formular um repelente com possível efeito mais prolongado, seguro e com um sensorial agradável. Durante o desenvolvimento foi possível identificar 17 compostos químicos por meio do espectro de massas, sendo o citronelal e citronelol como majoritários. O carreador lipídico nanoestruturado com óleo de citronela (CLN-OC) apresentou tamanho médio de partícula nanométrica de 350 nm. No ensaio de permeação cutânea ex vivo, utilizando como marcadores geraniol, citronelol e citronelal, observou-se que tanto o óleo de citronela livre quanto nanoencapsulado não sugere absorção, sendo seguro para uso tópico. No teste de eficácia in vivo, realizado com o mosquito Aedes aegypti, a mistura de 50,0% óleo de citronela livre e 50,0% encapsulado (OC/CLN-OC (1:1)) em emulsão óleo em água foi a proporção que apresentou maior ação repelente quando comparado ao óleo de citronela livre. O teste realizado com análise térmica sugere que o CLN- óleo de citronela elevou o ponto de ebulição em relação ao óleo de citronela livre, indicando assim, uma possível justificativa para o seu efeito prolongado. Conclui-se neste trabalho que os nanocarreadores desenvolvidos com óleo de citronela apresentarem-se estáveis, com nanopartículas com tamanho dentro do previsto e seguros para aplicação tópica. A mistura de óleo de citronela livre e encapsulado (OC/CLN-OC (1:1)), isto é, 50,0% na forma livre e 50,0% na forma encapsulada foi a proporção que apresentou o melhor resultado com efeito repelente.Mosquito-borne diseases affect millions of people worldwide each year and the use of repellent is an economically viable practice to prevent. Therefore, proposing safer alternatives, more lasting and effective effects against various insects is highly recommended. Natural repellents have shown good results in terms of their effectiveness and safety, such as citronella oil. The general objective of this work was to encapsulate citronella oil in a nanostructured lipid carrier (NLC) to formulate a repellent with a possible longer lasting effect, safe and with a pleasant sensation. During the development it was possible to identify 17 chemical compounds through the mass spectrum, with citronellal and citronellol being the majority. The nanostructured lipid carrier with citronella oil (NLC-CO) presented showed an average nanometric particle size of 350 nm. In the ex vivo skin permeation assay, using geraniol, citronellol and citronellal as markers, it was observed that both free and nanoencapsulated citronella oil did not suggest absorption, being safe for topical use. In the in vivo efficacy test, carried out with the Aedes aegypti mosquito, the mixture of 50.0% free citronella oil and 50.0% encapsulated (CO/NLC- CO) (1:1)) in oil-in-water emulsion was the proportion that presented the greatest repellent action. when compared to free citronella oil. The test performed with thermal analysis suggests that NLC-CO raised the boiling point in relation to free citronella oil, thus indicating a possible justification for its prolonged effect. It is concluded in this work that the nanocarriers developed with citronella oil are stable, with nanoparticles with the expected size and safe for topical application. The mixture of free and encapsulated citronella oil (CO/NLC-CO) (1:1)), that is, 50.0% in the free form and 50.0% in the encapsulated form, was the proportion that presented the best result with repellent effect.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 2016/25009-

Development of a Nanotechnology Matrix-Based Citronella Oil Insect Repellent to Obtain a Prolonged Effect and Evaluation of the Safety and Efficacy

Mosquito-borne diseases affect millions of people worldwide each year, and the use of a topically applied insect repellent is an economically viable preventative health practice. The general objective of this work was to encapsulate citronella oil (CO) in a nanostructured lipid carrier (NLC) to formulate a topical repellent with a long duration of efficacy on the skin and a good safety profile based on minimizing skin penetration. In the studied CO, the main chemical constituents of geraniol, citronellal, and citronellol were identified and subsequently used as markers for the in vitro skin permeation testing (IVPT). An optimal NLC encapsulating CO formulation was developed and had an average particle size of 350 nm. The NLC was then formulated in combination with CO at ratios of 2:1, 1:1, and 1:2 CO:NLC-CO as oil-in-water (O/W) emulsions and compared to CO in the same O/W emulsion base (all at 10% CO in the final O/W topical formulation). The markers geraniol, citronellol, and citronellal were detected in all samples tested F1 (10% CO in O/W emulsion) and F3 (10% CO/NLC-CO 1:1 in O/W emulsion). Even the percentages of F3 markers were higher than F1. The recovery of the percentage balance (based on the total remaining on the skin surface, on the skin, and penetrated through the skin to the receptor) of geraniol, citronellol, and citronellal markers for F1 and F3 was 7.70% and 11.96%; 25.51% and 31.89%; and 5.09% and 4.40%, respectively. The nanoparticle lipid solid forms a repellent reservoir on the skin surface, releasing the active ingredients slowly through volatilization, extending the repellent action, and reducing permeation through the skin. It is possible to assume that the remaining 92.30% and 88.03%; 74.49% and 68.11%; and 94.10% and 95.60% of geraniol, citronellol, and citronellal markers of F1 and F3, respectively, were lost to evaporation. In the in vivo efficacy test carried out with the Aedes aegypti mosquito, F3 was the optimal formulation, providing the greatest repellent action compared to free oil in O/W emulsion. Thermal analysis showed that the NLC-CO raised the boiling point of the encapsulated CO compared to the free oil, suggesting that the controlled release of the CO was a possible mechanism for its prolonged effect. We concluded that the nanocarriers developed with CO were stable and provided improved mosquito-repellent efficacy with minimal skin penetration of the CO actives over 24 h. Indeed, regardless of whether the CO was applied as free oil, a 1:1 mixture of CO (pure/free oil) or NLC-CO applied in an O/W emulsion can be considered safe for topical application due to minimal skin penetration