Liquid crystal precursor mucoadhesive system as a strategy to improve the prophylactic action of Syngonanthus nitens (Bong.) Ruhland against infection by Candida krusei

Matheus Aparecido dos Santos Ramos,1 Giovana Calixto,2 Luciani Gaspar de Toledo,3 Bruna Vidal Bonifácio,1 Lourdes Campaner dos Santos,4 Margarete Teresa Gottardo de Almeida,3 Marlus Chorilli,2 Taís Maria Bauab1 1Department of Biological Sciences, School of Pharmaceutical Sciences, 2Department of Drugs and Medicine, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, 3Department of Infectious Diseases, Faculty of Medicine of São José do Rio Preto, São José do Rio Preto, 4Department of Organic Chemistry, Chemistry Institute, São Paulo State University, Araraquara, São Paulo, Brazil Abstract: Vaginal infections caused by Candida krusei are a problem of extreme complexity due to the intrinsic resistance to azole drugs. The species Syngonanthus nitens (Bong.) Ruhland is a plant of the Eriocaulaceae family that has demonstrated promising antifungal activity. In phyto-formulation research, liquid crystal precursor mucoadhesive systems (LCPM) stand out as drug delivery systems for vaginal administration because they increase the activity and overcome the problems associated with plant-based medicines. Therefore, the objective of this study was to evaluate the potential of the methanolic extract of scapes of S. nitens (S. nitens extract [SNE]) and an SNE-loaded LCPM against C. krusei as prophylaxis for vulvovaginal candidiasis. LCPM formulation developed consisted of oleic acid as the oil phase (50% w/w), polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (40% w/w) as the surfactant and a polymeric dispersion containing 2.5% Carbopol® 974P and 2.5% polycarbophil (10% w/w) as the aqueous phase. LCPM formulation developed was characterized using polarized light microscopy, rheological analysis, and in vitro mucoadhesive studies. Different strains of C. krusei, including one standard strain (American Type Culture Collection 6258) and three clinically isolated strains from the vaginal region (CKV1, 2, and 3), were used to determine the minimum inhibitory concentration, inhibition of biofilms, and time kill. The in vivo prophylaxis assay was performed using the standard strain (American Type Culture Collection 6258). The analyses of F by polarized light microscopy and rheology showed isotropy; however, the addition of 100% artificial vaginal mucus (F100) made it more viscous and anisotropic. Moreover, the mucoadhesive strength was modified, which makes F an excellent formulation for vaginal applications. SNE was active against all strains studied, with minimum inhibitory concentration values ranging from 125 to 62.5 µg/mL; after incorporating SNE into F (FE), these values decreased to 62.5 to 31.2 µg/mL, demonstrating that incorporation into the formulation potentiated the action of SNE. Additionally, the time kill assays showed that both forms of SNE were capable of controlling growth, thereby suggesting a possible fungistatic mechanism. Unloaded SNE was not active against C. krusei biofilms, but FE was active against a clinical strain (CKV2). In vivo analysis showed that FE was able to prevent the development of infection following 10 days of administration. We concluded that the formulation developed in this study was an important vehicle for the delivery of SNE based on the improved antifungal activity in all in vitro and in vivo analyses. Furthermore, the extract incorporated into the system may serve as an important prophylactic agent against vaginal infections caused by C. krusei. Keywords: precursor system of mucoadhesive liquid crystal, nanostructured system, ­prophylaxis, Candida kruse

Nanostructured lipid system as a strategy to improve the anti-Candida albicans activity of Astronium sp.

Bruna Vidal Bonifácio,1 Matheus Aparecido dos Santos Ramos,1 Patrícia Bento da Silva,2 Kamila Maria Silveira Negri,1 Érica de Oliveira Lopes,1 Leonardo Perez de Souza,3 Wagner Vilegas,4 Fernando Rogério Pavan,1 Marlus Chorilli,2 Taís Maria Bauab11Department of Biological Sciences, 2Department of Drugs and Medicines, School of Pharmaceutical Sciences, 3Department of Organic Chemistry, Chemistry Institute, UNESP – Univ Estadual Paulista, Araraquara, São Paulo, Brazil; 4Coastal Campus of São Vicente, UNESP – Univ Estadual Paulista, São Vicente, São Paulo, BrazilAbstract: The genus Astronium (Anacardiaceae) includes species, such as Astronium fraxinifolium, Astronium graveolens, and Astronium urundeuva, which possess anti-inflammatory, anti-ulcerogenic, healing, and antimicrobial properties. Nanostructured lipid systems are able to potentiate the action of plant extracts, reducing the required dose and side effects and improving antimicrobial activity. This work aims to evaluate a nanostructured lipid system that was developed as a strategy to improve the anti-Candida albicans activity of hydroethanolic extracts of stems and leaves from Astronium sp. The antifungal activity against C. albicans (ATCC 18804) was evaluated in vitro by a microdilution technique. In addition to the in vitro assays, the Astronium sp. that showed the best antifungal activity and selectivity index was submitted to an in vivo assay using a model of vulvovaginal candidiasis infection. In these assays, the extracts were either used alone or were incorporated into the nanostructured lipid system (comprising 10% oil phase, 10% surfactant, and 80% aqueous phase). The results indicated a minimal inhibitory concentration of 125.00 µg/mL before incorporation into the nanostructured system; this activity was even more enhanced when this extract presented a minimal inhibitory concentration of 15.62 µg/mL after its incorporation. In vivo assay dates showed that the nanostructure-incorporated extract of A. urundeuva leaves was more effective than both the unincorporated extract and the antifungal positive control (amphotericin B). These results suggest that this nanostructured lipid system can be used in a strategy to improve the in vitro and in vivo anti-C. albicans activity of hydroethanolic extracts of Astronium sp.Keywords: plant extract, anticandidal activity, microdilution, microemulsion, vulvovaginal candidiasi

In vitro and in vivo activity of the nuclear factor-kappa B inhibitor sulfasalazine in human glioblastomas.

Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear factor (NF)-kappaB is constitutively activated in glioblastoma surgical samples, primary cultures, and cell lines and promotes their growth and survival. Sulfasalazine, an anti-inflammatory drug that specifically inhibits the activation of NF-kappaB, blocked the cell cycle and induced apoptosis in several glioblastoma cell lines and primary cultures, as did gene therapy with a vector encoding a super-repressor of NF-kappaB. In vivo, sulfasalazine also significantly inhibited the growth of experimental human glioblastomas in nude mice brains. Given the documented safety of sulfasalazine in humans, these results may lead the way to a new class of glioma treatment

Between Conflict and Cooperation - Global-National Interfaces and the Fight Against Hiv/Aids in Brazil and South Africa

This paper endeavours to analyse the relationship between Global Health Governance and national health politics in the case of HIV/AIDS. The paper compares Brazil and South Africa as two cases in which the relationship between national politics and GHG has been structured in contrasting ways, ranging from conflict to cooperation. Different reciprocal influences are analysed through the interface concept. A differentiation is made between four kinds of interfaces: resource-transfer, organisational, legal, and discursive. The main finding is that despite a huge variety of global actors operating in the field of HIV/AIDS, national politics and actor constellations account for most of the contrasts between Brazil and South Africa in respect to their fight against HIV/AIDS. In contrast to Brazil, South Africa's HIV/AIDS policy has for a long time been dominated by one central political actor. Until 2003, the central ANC-government was able to push through its strict refusal to provide antiretroviral drugs in the public health system