Chemical Characterization, Leishmanicidal Activity and In Vitro Cytotoxicity of the Essential Oil Extracted from Pectis brevipedunculata (Gardner) Sch.Bip. and Its Incorporation into Microemulsion Systems.

Pectis brevipedunculata (Gardner) Sch.Bip., known in Brazil as alecrim do campo, is a small Asteraceae family plant with a calming effect and consumed as tea. This species contains components, such as neral and geranial, that display various biological activities, such as leishmanicidal. The aim was to chemically characterize the essential oil (EO) obtained from P. brevipedunculata (EO-PB) by hydrodistillation and a microemulsion formulated with EO (ME-PB), Tween 80 and Transcutol P, assess the leishmanicidal effect against Leishmania (L.) amazonensis promastigotes and cytotoxicity against RAW 264.7. EO-PB and ME-PB were analyzed by Gas Chromatography Mass Spectrometry (GC/MS). Monoterpene hydrocarbons were noteworthy among the identified compounds. The main EO-PB constituents were α-pinene and limonene, followed by neral and geranial, which were maintained in ME-PB. EO-PB presented an inhibitory concentration (IC50) of 20 µg/mL and ME-PB of 0.93 µg/mL. ME-PB inhibition towards the parasite was 20-fold higher than that of EO-PB. This indicated that EO incorporation to the microemulsion resulted in optimized biological activity. Selectivity indices indicate that ME-PB is more selective concerning parasite inhibition. Thus, ME-PB may comprise an adequate approach against Leishmania, as the inhibitory concentration (IC50) promastigotes was lower than that considered toxic for cells cell cytotoxicity of 50% (CC50).

Evaluation of the acute toxicity of ellagic acid and gallic acid incorporated in Poloxamer407® gel, in Zophobas morio larvae.

Gallic acid (GA) has antioxidant, anti-inflammatory and antimicrobial properties, while ellagic acid (EA) demonstrates anticancer, antiviral and photoprotective activity. In this study, the combination of these substances incorporated into a poloxamer gel was tested to verify the individual effect of the substances, in addition to taking advantage of a probable complementary effect, aiming to provide additional therapeutic benefits. As a result of the incorporation, formulations containing GA, EA and GA + EA were obtained, which were evaluated for the effects of the Freeze-thaw cycle on pH, which revealed a significant decrease (p < 0.05) in most samples, including the vehicle (without drug) and the gel containing both drugs. No sample showed variation outside the normal pH range for the skin, with values ranging from 4.8 to 6.0. Regarding conductivity, the GA, EA and GA + EA formulations showed a reduction (p < 0.05) after the freeze-thaw cycle. The drug content in the formulations ranged from 95.86% to 101.35% initially to 91.30% to 101.51% after the freeze-thaw cycle. Regarding the drug release, the results revealed the following cumulative percentages: GA-3% - 92.58% after 1.5 h; AE-3% - 51.60% after 6 h; GA + EA (1.5% = 1.5%) - 99.91% after 2 h; GA + EA- (1.5% = 1.5%) released 57.06%, after 6 h. Regarding toxicity, it was observed that the group treated with GA showed a lower survival rate of the larvae (40%) at the dose 3000 mg/Kg in the formulation. Following the same trend, in the acute lethal concentration (ALC50) test performed using Zophobas morio larvae, an ALC50 of 2191.51 mg/Kg was observed for GA at 48 h. Melanin analysis showed a decrease in concentrations of 30 mg/Kg in the GA group, 3 mg/Kg of EA and 3, 300, 3000 mg/Kg of GA + EA, of the pure drugs. In the groups with the drugs incorporated into the gel, there was a significant decrease (P < 0.05) in melanin in the vehicle (gel), at concentrations of 300 and 3000 mg/Kg of GA and EA. On the other hand, in the combination of GA + EA, a reduction was observed at concentrations of 3 and 30 mg/Kg when compared to the control group. Thus, the gel showed good quality as a pharmaceutical formulation for topical use and low toxicity, making it promising for use in skin therapies.

Uso dos antifúngicos no tratamento da candidíase vulvovaginal: uma revisão integrativa / Use of antifungals in the treatment of vulvovaginal candidiasis: an integrative review

Objective: To identify scientific evidence available in the literature and analyze the action of antifungal drugs used for the treatment of vulvovaginal candidiasis. Methods:Integrative literature review conducted in the databases Medline/PubMed, Embase, Web of Science, Cochrane Library, CINAHL, SCOPUS and VHL; with the descriptors "woman", "antifungal agents"; "vulvovaginal candidiasis". Results:Ten scientific articles published between 1983 and 2020 were obtained. Of these, four were developed in Iran; followed by Mexico, England, Taiwan, Thailand, Denmark, and the United States. In terms of methodological design, most studies are clinical trials (n=8), and two are cross-sectional studies. Regarding the level of evidence, eight are level II, and only two investigations are level IV. Concerning the antifungal drugs used in the treatment, there was a predominance of clotrimazole (n=4; efficacy ranging from 42.4% to 98.3%), followed by econazole (n=2; efficacy between 39% and 89%), combined or not with another antifungal drug. Conclusion: The use of clotrimazole stands out, as it is highly effective in the treatment of vulvovaginal candidiasis. This study contributes to the advancement of knowledge and improvement of the clinical practice of nursing and other health professionals. It is expected that these results will encourage further studies and update clinical practices.Descriptors:Women;Antifungal Agents;Candidiasis, Vulvovaginal

Objective: To identify scientific evidence available in the literature and analyze the action of antifungal drugs used for the treatment of vulvovaginal candidiasis. Methods: Integrative literature review conducted in the databases Medline/PubMed, Embase, Web of Science, Cochrane Library, CINAHL, SCOPUS and VHL; with the descriptors "woman", "antifungal agents"; "vulvovaginal candidiasis". Results:Ten scientific articles published between 1983 and 2020 were obtained. Of these, four were developed in Iran; followed by Mexico, England, Taiwan, Thailand, Denmark, and the United States. In terms of methodological design, most studies are clinical trials (n=8), and two are cross-sectional studies. Regarding the level of evidence, eight are level II, and only two investigations are level IV. Concerning the antifungal drugs used in the treatment, there was a predominance of clotrimazole (n=4; efficacy ranging from 42.4% to 98.3%), followed by econazole (n=2; efficacy between 39% and 89%), combined or not with another antifungal drug. Conclusion:The use of clotrimazole stands out, as it is highly effective in the treatment of vulvovaginal candidiasis. This study contributes to the advancement of knowledge and improvement of the clinical practice of nursing and other health professionals. It is expected that these results will encourage further studies and update clinical practices.Descriptors:Women;Antifungal Agents;Candidiasis, Vulvovaginal

Innovative Microemulsion Loaded with Unusual Dimeric Flavonoids from Fridericia platyphylla (Cham.) L.G. Lohmann Roots.

Fridericia platyphylla (Cham.) L.G. Lohmann is a species native to the Brazilian cerrado, with promising bioactivity. The organic fraction of the roots is rich in unusual dimeric flavonoids, reported as potential candidates for cancer treatment. The exploration of these flavonoids is very important, considering their diverse biological activities and the need for innovative therapeutic options. This work aimed to develop and characterize a microemulsion loaded with a non-polar fraction (DCM). The constituents were chosen, and the pseudo-ternary diagram was constructed to determine the region of microemulsion formation. The microemulsions blank (ME), with 3% (ME3) and 5% (ME5) of fraction DCM, were characterized in terms of droplet size, zeta potential, and polydispersity index. Both MEs showed particle sizes <100 nm; only ME3 exhibited better values for polydispersity index and zeta potential and was therefore selected for further study. The organoleptic and physicochemical characteristics were evaluated, revealing limpidity and transparency typical of these microstructures, physiologically acceptable pH, refractive index of 1.42±0.01, and density of 1.017 g/cm3±0.01. The stability tests showed good stability profiles even after exposure to extreme thermal conditions, with minimal changes in pH and the content of the incorporated fraction. The in vitro release study demonstrated that ME3 enabled the controlled release of the fraction, with a cumulative amount released over 60% within 6 h. Furthermore, fraction DCM and ME3 exhibited no toxicity in Tenebrio molitor larvae. The developed microemulsion exhibited excellent properties, so this study represents the first successful attempt to develop a formulation that incorporates the dimeric flavonoid fraction.

Films composed of white angico gum and chitosan containing chlorhexidine as an antimicrobial agent.

Anadenanthera colubrina, popularly known as white angico, is a species extensively cultivated in Brazil, mainly in the cerrado region, including the state of Piauí. This study examines the development of films composed of white angico gum (WAG) and chitosan (CHI) and containing chlorhexidine (CHX), an antimicrobial agent. The solvent casting method was used to prepare films. Different combinations and concentrations of WAG and CHI were used to obtain films with good physicochemical characteristics. Properties such as the in vitro swelling ratio, the disintegration time, folding endurance, and the drug content were determined. The selected formulations were characterised by scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction, and the CHX release time and antimicrobial activity were evaluated. CHX showed a homogenous distribution in all CHI/WAG film formulations. The optimised films showed good physicochemical properties with 80% CHX release over 26 h, which is considered promising for local treatment of severe lesions in the mouth. Cytotoxicity tests of the films did not show toxicity. The antimicrobial and antifungal effects were very effective against the tested microorganisms.

Anti-inflamatórios não esteroides tópicos para o alívio da dor artritica, beneficios para idosos / Non-steroid anti-inflammatory topics for arthritic pain relief, benefits for elderly / Temas antiinflamatorios no esteroides para el alívio del dolor artritico, beneficios para personas mayores

Objetivo: Identificar e analisar os anti-inflamatórios não esteroides tópicos para o alívio da dor artrítica, benefícios para idosos. Métodos: Trata-se de uma revisão integrativa realizada nas bases de dados no mês de maio de 2020, mediante consulta às bases de dados MEDLINE/PubMed, CINAHL, EMBASE, Web of Science, SCOPUS e índice bibliométrico LILACS, acessados por meio do Portal Periódicos da Comissão de Aperfeiçoamento de Pessoal de Ensino Superior, utilizando os descritores: idoso (Aged/elderly), anti-inflamatório não esteroide (Anti-Inflammatory Agents, Non-Steroidal) artrite (Arthritides/Polyarthritis). No qual foram selecionados 13 artigos sem limitador para tempo e idioma. Resultados: Detectou se que as variáveis mais evidenciadas foram: inglês (100%); artigos indexados na MEDLINE/PubMed (69,2%); pais com mais publicações Inglaterra (46%). Destaca-se que 69,3% dos artigos foram ensaios clínicos randomizados controlados; anti-inflamatório tópico mais usado diclofenaco sódico (61,5% seguido do cetoprofeno (38,7%). Conclusão: Concluiu se o diclofenaco e o cetoprofeno apresentam eficácia e segurança no alívio da dor artrítica, e baixa toxicidade cutânea local. (AU)

Objective To identify and analyze topical non-steroidal anti-inflammatory drugs for the relief of arthritic pain, benefits for the elderly. Methods: This is an integrative review carried out on the databases in May 2020, by consulting the MEDLINE / PubMed, CINAHL, EMBASE, Web of Science, SCOPUS and LILACS bibliometric index databases, accessed through the Portal Journals of the Higher Education Personnel Improvement Commission, using the descriptors: elderly (Aged / elderly), non-steroidal anti-inflammatory (Anti-Inflammatory Agents, Non Steroidal) arthritis (Arthritides / Polyarthritis). In which 13 articles were selected without time and language limitations. Results: It was found that the most evident variables were: English (100%); articles indexed in MEDLINE / PubMed (69.2%); parents with the most publications in England (46%). It is noteworthy that 69.3% of the articles were randomized controlled clinical trials; most commonly used topical anti-inflammatory diclofenac sodium (61.5% followed by ketoprofen (38.7%). Conclusion: Diclofenac and ketoprofen were concluded to be effective and safe in relieving arthritic pain and low local skin toxicity. (AU)

Objetivo: Identificar y analizar medicamentos antiinflamatorios no esteroideos tópicos para el alivio del dolor artrítico, beneficios para los ancianos. Métodos: Esta es una revisión integradora realizada en las bases de datos en mayo de 2020, consultando las bases de datos del índice bibliométrico MEDLINE / PubMed, CINAHL, EMBASE, Web of Science, SCOPUS y LILACS, a las que se accede a través del Portal Revistas de la Comisión de Mejoramiento del Personal de Educación Superior, utilizando los descriptores: artritis de edad avanzada (Ancianos / ancianos), antiinflamatorios no esteroideos (agentes antiinflamatorios, no esteroideos) (artritis / poliartritis). En el que se seleccionaron 13 artículos sin limitaciones de tiempo e idioma. Resultados: se encontró que las variables más evidentes fueron: inglés (100%); artículos indexados en MEDLINE / PubMed (69,2%); padres con más publicaciones en Inglaterra (46%). Es de destacar que el 69,3% de los artículos fueron ensayos clínicos controlados aleatorios; diclofenaco sódico antiinflamatorio tópico más utilizado (61.5% seguido de ketoprofeno (38.7%). Conclusión: Se concluyó que el diclofenaco y el ketoprofeno son efectivos y seguros para aliviar el dolor artrítico y la baja toxicidad local de la piel. (AU)

Nanostructured Lipid Carriers as a Novel Strategy for Topical Antifungal Therapy.

Nanostructured lipid carriers (NLC) were developed as an alternative carrier system optimizing limitations found in topical treatments for superficial fungal infections, such as limited permeation through the skin. However, few published studies are focused on standardization and characterization of determinant variables of these lipid nanosystems' quality. Thus, this systematic review aims to compile information regarding the selection of lipids, surfactants, and preparation method that intimately relates to the final quality of this nanotechnology. For this, the search was carried with the following descriptors: 'nanostructured lipid carriers', 'topical', 'antifungal' separated by the Boolean operators 'and', present in the titles of the databases: Science Direct, Scopus and Pubmed. The review included experimental articles focused on the development of nanostructured lipid carriers targeted for topical application with antifungal activity, published from 2015 to 2021. Review articles, clinical studies, and studies on the development of other nanocarriers intended for other routes of administration were excluded from the study. The research included 26 articles, of which 58% were developed in India and Brazil, 53% published in the years 2019 and 2020. As for the selection of antifungal drugs incorporated into NLCs, the azole class had a preference over other classes, voriconazole being incorporated into 5 of the 26 developed NLC studied. It was also observed a predominance of medium chain triglycerides (MCT) as a liquid lipid and polysorbate 80 as a surfactant. Among other results, this review compiles the influences of each of the variables discussed in the quality parameters of NLCs, in order to guide future research involving the development of this technology. Graphical Abstract.

Atividades farmacológicas da manteiga de bacuri (Platonia insignis Mart): revisão integrativa / Pharmacological actions of bacuri butter (Platonia insignis Mart): an integrative review

RESUMO Objetivo identificar as atividades farmacológicas da manteiga de bacuri (Platonia insignis Mart.). Métodos revisão integrativa, realizada nas bases de dados Literatura Latino-americana e do Caribe em Ciências da Saúde, Cumulative Index to Nursing and Allied Health Literature, EMBASE, MEDLINE/PubMed, Web of Science, Cochrane Library e SCOPUS, sem delimitação temporal e de idioma. A seleção se constituiu de 13 ensaios pré-clínicos. A avaliação das informações ocorreu de forma descritiva, confrontando com os achados pertinentes. Resultados observou-se que 50,0% das publicações foram indexadas na MEDLINE/PubMed, maioria das publicações ocorreram na Inglaterra (61,5%), seguidas do Brasil e dos Estados Unidos, ambos com 13,3%. Destaca-se que 100,0% dos artigos foram ensaios pré-clínicos; atividades farmacológicas para antioxidante (38,4%) e antileishmanicidas (30,7%). Registrou-se que 38,4% dos ensaios apresentaram testes de toxicidade. Conclusão a manteiga de bacuri (Platonia insignis Mart.) apresentou atividades farmacológicas em ensaios pré-clínicos, como antioxidantes, antileshimaniose, anticonvulsivante e cicatrização de feridas.

ABSTRACT Objective to identify the pharmacological activities of bacuri butter (Platonia insignis Mart.). Methods an integrative review, carried out in the databases of Latin American and Caribbean Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature, EMBASE, MEDLINE/PubMed, Web of Science, Cochrane Library and SCOPUS, without the time and language restriction. The selection consisted of 13 pre-clinical trials. The information assessment descriptively took place, comparing with the pertinent findings. Results it was observed that 50.0% of the publications were indexed in MEDLINE/PubMed, most publications were from England (61.5%), followed by Brazil and the United States, both with 13.3%. It is noteworthy that 100.0% of the articles were pre-clinical trials; pharmacological activities for antioxidants (38.4%) and antileishmanicides (30.7%). It was found that 38.4% of the trials presented toxicity tests. Conclusion bacuri butter (Platonia insignis Mart.) Showed pharmacological activities in pre-clinical trials, such as antioxidants, antileshimaniasis, anticonvulsant and wound healing.

Development of Chlorhexidine Digluconate and Lippia sidoides Essential Oil Loaded in Microemulsion for Disinfection of Dental Root Canals: Substantivity Profile and Antimicrobial Activity.

The dental intracanal disinfection is crucial to achieve the success of endodontic treatment, avoiding the maintenance of endodontic infections. Chlorhexidine digluconate can act as an irrigating agent for it. However, it can cause tissue irritation in high concentrations. Therefore, combinations with other antimicrobial agents and more efficient therapeutic alternatives are studied, which make it possible to administer drugs more safely and with minimal adverse effects. Thus, the objective of this study was the development of a microemulsion containing chlorhexidine digluconate and essential oil of Lippia sidoides to be used for disinfection of dental root canals and to evaluate its profile of substantivity and antimicrobial activity. The microemulsions were obtained through phase diagrams, using the spontaneous formation method. We completed a physical-chemical characterization and evaluate the stability of the microemulsions, in addition to the substantivity profile in a bovine root dentin model, and in vitro antibacterial effect on Enterococcus faecalis. A method for quantifying chlorhexidine was developed using UV-Vis spectroscopy. The microemulsions showed acid pH, conductivity above 1.3 µScm-1, and dispersion index similar to water. The microemulsions showed antimicrobial inhibition halos similar to the commercial gel conventionally used, but with four times more substantivity to dentinal tissues. Microemulsions were obtained as a therapeutic alternative to formulations available on the market, presenting themselves as a system with great potential for the administration of drugs for disinfection of root canals.

Gallic and Ellagic Acids Are Promising Adjuvants to Conventional Amphotericin B for the Treatment of Cutaneous Leishmaniasis.

In this study, we demonstrated the potential associative effect of combining conventional amphotericin B (Amph B) with gallic acid (GA) and with ellagic acid (EA) in topical formulations for the treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests of the formulations and in vitro drug release studies with Amph B, GA, Amph B plus GA, EA, and Amph B plus EA were carried out, as well as assessment of the in vivo treatment of BALB/c mice infected with Leishmania major After 40 days of infection, the animals were divided into 6 groups and treated twice a day for 21 days with a gel containing Amph B, GA, Amph B plus GA, EA, or Amph B plus EA, and the negative-control group was treated with the vehicle. In the animals that received treatment, there was reduction of the lesion size and reduction of the parasitic load. Histopathological analysis of the treatments with GA, EA, and combinations with Amph B showed circumscribed lesions with the presence of fibroblasts, granulation tissue, and collagen deposition, as well as the presence of activated macrophages. The formulations containing GA and EA activated macrophages in all evaluated parameters, resulting in the activation of cells of the innate immune response, which can generate healing and protection. GA and EA produced an associative effect with Amph B, which makes them promising for use with conventional Amph B in the treatment of cutaneous leishmaniasis.

Development of microemulsion of tamsulosin and dutasteride for benign prostatic hyperplasia therapy.

Benign prostatic hyperplasia (BPH) is a condition characterized by a benign enlargement of the prostate that interferes with the normal flow of urine. This disease is treated with the oral administration of combination therapy comprising α-blockers (tamsulosin) and 5α-reductase inhibitors (dutasteride). However, these compounds have low bioavailability. Thus, transdermal microemulsions aimed at promoting permeation and efficient targeted drug delivery through the skin are used. The objectives of this study were to obtain microemulsions of the combined doses of dutasteride and tamsulosin and evaluate their anti-hyperplastic activity in vivo. A phase diagram (4:1) was obtained for the choice of microemulsions. The microemulsions were characterized in terms of the droplet size, rheology, pH, conductivity, refractive index, in vitro release profile, and antihyperplastic effect in vivo. A method for the simultaneous quantification of drugs was developed using UV-vis spectroscopy. The microemulsions had an average size less than 116 nm, an acidic pH and low viscosity. The conductivity ranged from 6.18 to 185.2 µS/cm. The in vitro release profile was sustained for 6 h. Microemulsions promoted the reduction in the size of testosterone-dependent organs (prostate and seminal vesicles). Transdermal formulations for the treatment of BPH were obtained as a therapeutic alternative to conventional treatments.

Antidepressant-like effect of anacardic acid in mice via the L-arginine-nitric oxide-serotonergic system.

Depression, a multifactorial neuronal disorder with high morbidity/mortality, is associated with psychological, psychosocial, hereditary, and environmental etiologies, where reactive species exert pathophysiological functions. Anacardic acid (AA), a natural compound obtained from cashew nut liquid, has several pharmacological activities, including antioxidant and anticonvulsant. The aim of the present study was to evaluate the antidepressant-like effect of AA and the involvement of serotonergic, noradrenergic, and L-arginine-nitric oxide (NO) in tail suspension and forced swim tests and, more so, to investigate its antioxidant effect in Saccharomyces cerevisiae and in male Swiss mice (n = 8). In order to identify the antidepressant mechanisms, AA (10, 25, or 50 mg/kg, p.o.) was given 30 min before clonidine (2-adrenergic receptor agonist), L-arginine (NO precursor), propranolol (ß-adrenergic receptor antagonist), and several other agonists or antagonists used. On the other hand, clonidine, noradrenoreceptor, noradrenaline, and L-arginine were used to identify the antidepressant mechanisms. Results suggest that AA exerts antidepressant-like activity, especially at higher doses, possibly by inhibiting serotonin and 5HT-1A reuptake receptors and by inhibiting NO synthetase and guanylyl cyclase enzymes. Additionally, AA exhibited antioxidant effect in S. cerevisiae. This antioxidant capacity may be linked to its antidepressant-like effect but does not interact with α- and ß-adrenoceptor receptors. In conclusion, AA may be used as a promising agent to treat depression, especially which arises from oxidative stress.

Amphotericin B-Loaded Emulgel: Effect of Chemical Enhancers on the Release Profile and Antileishmanial Activity In Vitro.

Cutaneous leishmaniasis is a neglected parasitic disease. Treatment is preferably performed with pentavalent antimony associated or not with amphotericin B (AmB). This study aimed to develop an emulgel with different chemical enhancers of cutaneous release. Initially, AmB emulsions were obtained with the chemical promoters, oleic acid and geraniol and without promoter, then for the evaluation of the formulations, a preliminary stability study was carried out where the formulations were submitted to centrifugation, before and after the freeze-thaw cycle and analyzed appearance, color, pH, spreadability, viscosity, conductivity, droplet size, assay, in vitro release study, in vitro antileishmania activity in Leishmania major promastigotes, and macrophage toxicity in the MTT test. The emulsions were yellowish, with no signs of instability after the centrifugation test. The pH range corresponded to that of the skin, which is 4.6 to 5.8, before and after the freeze-thaw cycle, the formulations had good spreadability and did not present significant viscosity differences before and after the freeze-thaw cycle, presenting a non-Newtonian characteristic. AmB content was within the kinetic model of zero order release, the formulation of 3% AmB and 5% oleic acid (formulation 1) was chosen to proceed with the antileishmania activity test and showed potential activity against the in vitro parasite with significant reduction of cytotoxicity on murine macrophages, indicating that the formulation is promising for the treatment of cutaneous leishmaniasis.

Third-Generation Transdermal Delivery Systems Containing Zidovudine: Effect of the Combination of Different Chemical Enhancers and a Microemulsion System.

This study aimed to examine the influence of the combination of chemical enhancers and a microemulsion on the transdermal permeation of zidovudine (AZT). Ethanol, 1,8-cineole, and geraniol were incorporated in a microemulsion. The droplet size, zeta potential, rheology, and SAXS analysis were performed. The permeation enhancer effect was evaluated using pig ear skin. Snake skin (Boa constrictor) treated with the formulations was also used as a stratum corneum model and studied by attenuated total reflectance-infrared spectroscopy. As a result, it was observed that the incorporation of the chemical enhancers promoted a decrease of the droplet size and some rheological modifications. The 1,8-cineole associated with the microemulsion significantly increased the permeated amount of AZT. Conversely, ethanol significantly increased the quantity of the drug retained in the skin. The probable mechanism for the cineole and ethanol effects was respectively: fluidization and increasing of the diffusion coefficient, and increasing of the partition coefficient. Surprising, geraniol + microemulsion drastically decreased both the permeated and the retained amount of AZT into the skin. Thus, the adequate association of microemulsion and chemical enhancers showed to be a crucial step to enable the topical or transdermal use of drugs.

Technological development of microemulsions with perspectives for pain treatment: a patent review.

INTRODUCTION: Microemulsions are thermodynamically stable translucent systems widely used for systemic delivery of drugs. The present study is the first to analyze the biotechnological potential of microemulsion systems for therapeutic purposes, through transdermal route, for pain treatment. AREAS COVERED: Patents were searched in the World Intellectual Property Organization (WIPO), European Patent Office (Espacenet), United States Patent and Trademark Office (USPTO) and National Institute of Intellectual Property (INPI). The inclusion criteria were published patents containing the keywords; 'microemulsion' and 'transdermal' in their title or abstract. 208 patents were found. However, only those patents which mentioned in their abstract or in their description the use of microemulsion system (object of invention) for pain treatment were selected. Were excluded duplicate patents and those that did not report pharmacological use of MEs specifically for pain treatment. Thus, sixteen patents were selected and described in the present study. EXPERT OPINION: Patents were found that focused specifically on the development process of microemulsion systems, the inclusion of essential oils in microemulsions, which place microemulsions as delivery systems for NSAIDs and other substances, as well as microemulsions for transdermal administration. These studies reinforce the therapeutic applicability of MEs in the treatment of acute and chronic pain.

Emulgel based on amphotericin B and bacuri butter (Platonia insignis Mart.) for the treatment of cutaneous leishmaniasis: characterization and in vitro assays.

OBJECTIVE: This work aimed to develop and characterize a topical emulgel of amphotericin B (AmB) with bacuri butter (Platonia insignis Mart.) and evaluate its antileishmanial activity using in vitro assays. SIGNIFICANCE: Leishmaniasis is considered an infectious disease, with high incidence and capacity to produce deformities. The first-line treatment recommended by WHO, with pentavalent antimonials, is aggressive and very toxic. Therefore, the development of topical treatments can emerge as a promising and less offensive alternative. METHODS: The developed formulations were evaluated for organoleptic characteristics, centrifugation resistance, globule size, pH, electrical conductivity, viscosity, spreadability, drug content, preliminary stability, in vitro release profile, evaluation of antileishmanial activity using promastigotes forms of Leishmania major as infecting agents, macrophage cytotoxicity and selectivity index (IS). RESULTS: Formulated emulsions presented organoleptic characteristics compatible with its constituents; pH values were suitable for topical application, ranging from 4.73 to 5.02; introduced non-Newtonian shear thinning system; drug content was within the established standards, and the most suitable kinetic model of release was the first order. Regarding the in vitro assays, formulations containing both 1% and 3% of AmB presented similar outcomes, indicating a synergism between the bacuri butter and the drug, possibly showing a reduction on cytotoxicity to host cells. CONCLUSIONS: It was concluded that the formulations developed showed promising antileishmanial action and high potential for topical use.

Evaluation of Microemulsion and Lamellar Liquid Crystalline Systems for Transdermal Zidovudine Delivery.

This study proposed to investigate and to compare colloidal carrier systems containing Zidovudine (3'-azido-3'-deoxythymidine) (AZT) for transdermal administration and optimization of antiretroviral therapy. Microemulsion (ME) and lamellar phase (LP) liquid crystal were obtained and selected from pseudoternary diagrams previously developed. Small-angle X-ray scattering and rheology analysis confirmed the presence of typical ME and liquid crystalline structures with lamellar arrangement, respectively. Both colloidal carrier systems, ME, and LP remained stable, homogeneous, and isotropic after AZT addition. In vitro permeation study (using pig ear skin) showed that the amount of permeated drug was higher for ME compared to the control and LP, obtaining a permeation enhancing effect on the order of approximately 2-fold (p < 0.05). Microscopic examination after in vivo skin irritation studies using mice suggested few histological changes in the skin of animals treated with the ME compared to the control group (hydrogel). Thus, ME proved to be adequate and have promising effects, being able to promote the drug permeation without causing apparent skin irritation. On the order hand, LP functioned as a drug reservoir reducing AZT partitioning into the skin.

Evaluation of the in vivo leishmanicidal activity of amphotericin B emulgel: An alternative for the treatment of skin leishmaniasis.

The American Cutaneous Leishmaniasis (ACL) is an infectious disease that can be fatal. The first line of treatment is pentavalent antimonies. However, due to its potential to develop resistance, Amphotericin B (AmB) started to be used as an alternative medicine. Current treatments are limited, a fact that has led to a growing interesting in developing new therapies. This study aims to evaluate the therapeutic potential in vivo of an amphotericin B + oleic acid (OA) emulgel in the treatment of cutaneous leishmaniasis in an experimental model. Strains of Leishmania major MHOM/IL/80/Friendlin of Leishmania major were used. The animals were inoculated subcutaneously. After the development of leishmanial, nodular or ulcerative lesions, the animals were divided into three groups (control, Group A and Group B) and treated twice a day for twelve days. The weight of the animals was measured and the size of the lesions was observed. A histopathological analysis was performed with skin fragments of lesions and with the spleen of animals treated with different treatments (emulgel, AmB 3% emulgel and AmB 3% plus OA 5% emulgel). It was observed that when subjected to treatment with AmB 3% emulgel during the study period using both formulations, with enhancer and without enhancer, ulcerative lesions regress gradually or even complete cure. The quantification of the average number of parasites recovered from the inoculation site was made after the treatment in each group and the differences were considered significant. The treatment with AmB 3% and OA 5% emulgel had the best in vivo therapeutic response, showing good prospects for cutaneous leishmaniasis therapy as an alternative therapy.

Phenobarbital loaded microemulsion: development, kinetic release and quality control

ABSTRACT This study aimed to obtain and characterize a microemulsion (ME) containing phenobarbital (PB). The PB was incorporated in the proportion of 5% and 10% in a microemulsion system containing Labrasol(r), ethanol, isopropyl myristate and purified water. The physicochemical characterization was performed and the primary stability of the ME was evaluated. An analytical method was developed using spectrophotometry in UV  = 242 nm. The kinetics of the in vitro release (Franz model) of the ME and the emulsion (EM) containing PB was evaluated. The incorporation of PB into ME at concentrations of 5 and 10% did not change pH and resistance to centrifugation. There was an increase in particle size, a decrease of conductivity and a change in the refractive index in relation to placebo ME. The ME remained stable in preliminary stability tests. The analytical method proved to be specific, linear, precise, accurate and robust. Regarding the kinetics of the in vitro release, ME obtained an in vitro release profile greater than the EM containing PB. Thus, the obtained ME has a potential for future transdermal application, being able to compose a drug delivery system for the treatment of epilepsy.

RESUMO O objetivo deste trabalho foi obter e caracterizar uma microemulsão (ME) contendo fenobarbital (FEN). O FEN foi incorporado na proporção de 5% e 10% em um sistema microemulsionado composto por labrasol(r), etanol, miristato de isopropila e água purificada. Foi realizada a caracterização físico-química e avaliada a estabilidade preliminar da ME. Desenvolveu-se um método analítico por espectrofotometria em UV  = 242 nm. Foi avaliada a cinética de liberação in vitro (em modelo de Franz) da ME e da emulsão (EM) contendo FEN. A incorporação do FEN em ME nas concentrações de 5 e 10% não alterou o pH e a resistência à centrifugação. Houve aumento do tamanho da partícula, redução da condutividade e alteração do índice de refração em relação à ME placebo. A ME manteve-se estável nos ensaios de estabilidade preliminar. O método analítico demonstrou ser específico, linear, preciso, exato e robusto. Na cinética de liberação in vitro, a ME obteve um perfil de liberação in vitro superior a EM contendo FEN. Desta forma, a ME obtida tem potencial para uma futura aplicação transdérmica, podendo compor um sistema de liberação de fármacos para tratamento da epilepsia.