Desenvolvimento e caracterização de sistemas nanoestruturados para potencial administração nasal de zidovudina

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Citotoxicidade da Punica granatum L. (romã) sobre cultura de fibroblastos e de células de linhagem cancerígena

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Espectroscopia FT-Raman no diagnóstico do carcinoma espinocelular de mucosa bucal: estudo ex vivo em humanos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Análise químico-farmacêutica e estudos de estabilidade e de dissolução de comprimidos de orbifloxacino

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estabilidade, polimorfismo, dissolução e correlação in vivo-in vitro de Darunavir comprimidos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma

Background: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear.Methods: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ.Results: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation.Conclusions: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Presença de Microorganismos dos gêneros staphyococcus e candida na cavidade bucal humana

Pós-graduação em Biopatologia Bucal - ICT

Preparation and Characterization of Chitosan Nanoparticles for Zidovudine Nasal Delivery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desenvolvimento de nanopartículas de quitosana para adminstração nasal de zidovudina

Zidovudine (AZT) is the drug most commonly used in AIDS treatment, isolated or in combination with other antiretroviral agents, but it has certain limitations due to its therapeutic dose-dependent haematological toxicity. In addition, it has low oral bioavailability, since it undergoes pre-systemic metabolism. The nasal route has been used as an alternative route for drug administration, because it can promote its direct absorption to blood circulation, avoiding hepatic metabolism. However, this route presents as a factor limiting the mucociliary clearance mechanisms that remove quickly the formulation of the nasal cavity. To prolong the residence time of formulations, in this direction, has been proposed the development of mucoadhesive systems. Among the various existing systems, the use of chitosan (QS), as mucoadhesive polymer, has been widely exploited in the preparation of nanoparticles (NPs). The objective of this study was to develop and characterize QS’s NPs for intranasal administration of AZT. For both NPs have been developed by ionic crosslinking of QS with sodium tripolyphosphate (TPP). These NPs were characterized by studies of particle size distribution, zeta potential, morphology, mucoadhesion tests, assessing the ability of encapsulation of the drug and permeation profile of AZT. The evaluation of AZT in the NPs was determined by UV-Vis spectroscopy. Mucoadhesion measures were made using a texture analyzer, using a mucin disk and porcine mucous membrane , and permeation assay were conducted using porcine nasal mucous membrane adapted to the Franz cell. These results suggest that the systems in hand have great potential for nasal AZT administration

Ação da histatina 5, uma proteína antimicrobiana, no desenvolvimento de biofilmes de Candida Albicans

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fatores de virulência e infecção epitelial in vitro de biofilmes simples e mistos de Cndida albicans, Staphylococcus aureus sensível (MSSA) e resistente à meticilina (MRSA)

Pós-graduação em Reabilitação Oral - FOAR

Curcumin pharmacokinetic and pharmacodynamic evidences in streptozotocin-diabetic rats support the antidiabetic activity to be via metabolite(s)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Pharmacokinetics of hydroxymethylnitrofurazone and its parent drug nitrofurazone in rabbits

The prodrug hydroximethylnitrofurazone (NFOH) presents antichagasic activity with greatly reduced toxicity compared to its drug matrix nitrofurazone (NF). Besides these new characteristics, the prodrug was more active against the parasite T. cruzi amastigotes. These advantages make the prodrug a possible therapeutic alternative for the treatment of both acute and the chronic phase of Chagas disease. However, the knowledge of pharmacokinetic profile is crucial to evaluate the feasibility of a new drug. In this study, our objective was to evaluate the in vivo formation of NF from the NFOH single administration and to evaluate its pharmacokinetic profile and compared it to NF administration. A bioanalytical method to determine the NF and NFOH by LCMS/MS was developed and validated to perform these investigations. Male albino rabbits (n=15) received NF intravenously and orally in doses of 6.35 and 63.5 mg / kg respectively, and NFOH, 80.5 mg / kg orally. The serial blood samples were processed and analyzed by mass spectrometry. The system operated in positive and negative modes for the analites determination, under elution of the mobile phase 50:50 water: methanol. The administration of NFOH allowed the calculation of pharmacokinetic parameters for the prodrug, and the NF obtained from NFOH administration. Using the pharmacokinetic profile obtained from the NF i.v. administration, the oral bioavailability of NF from the administered prodrug was obtained (60.1%) and, as a key parameter in a prodrug administration, should be considered in future studies. The i.v. and oral administrations of NF differ in the constant of elimination (0.04 vs 0.002) and elimination half-life (17.32 min vs 276.09 min) due to the low solubility of the drug that hinders the formation of molecular dispersions in the digestory tract. Still, there was observed no statistical differences were observed between the pharmacokinetic parameters of orally administered NF and NF obtained from NFOH. The calculated area under the curve (AUC 0-∞) showed that the exposure to the parental drug was fairly the same (844.79 vs 566.44) for NF and NF obtained from the prodrug administration. The tendency to higher NF's mean residence time (MRT) as observed in the prodrug administration (956.1 min vs 496.3 min) guarantees longer time for the action of the drug and it allows the expansion of the administration intervals. These findings, added with the beneficial characteristics of the prodrug encourage new efficacy tests towards the clinical use of NFOH.

A curcumin-loaded liquid crystal precursor mucoadhesive system for the treatment of vaginal candidiasis

Women often develop vaginal infections that are caused primarily by organisms of the genus Candida. The current treatments of vaginal candidiasis usually involve azole-based antifungals, though fungal resistance to these compounds has become prevalent. Therefore, much attention has been given to molecules with antifungal properties from natural sources, such as curcumin (CUR). However, CUR has poor solubility in aqueous solvents and poor oral bioavailability. This study attempted to overcome this problem by developing, characterizing, and evaluating the in vitro antifungal action of a CUR-loaded liquid crystal precursor mucoadhesive system (LCPM) for vaginal administration. A low-viscosity LCPM (F) consisting of 40% wt/wt polyoxpropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, 50% wt/wt oleic acid, and 10% wt/wt chitosan dispersion at 0.5% with the addition of 16% poloxamer 407 was developed to take advantage of the lyotropic phase behavior of this formulation. Notably, F could transform into liquid crystal systems when diluted with artificial vaginal mucus at ratios of 1:3 and 1:1 (wt/wt), resulting in the formation of F30 and F100, respectively. Polarized light microscopy and rheological studies revealed that F behaved like an isotropic formulation, whereas F30 and F100 behaved like an anisotropic liquid crystalline system (LCS). Moreover, F30 and F100 presented higher mucoadhesion to porcine vaginal mucosa than F. The analysis of the in vitro activity against Candida albicans revealed that CUR-loaded F was more potent against standard and clinical strains compared with a CUR solution. Therefore, the vaginal administration of CUR-loaded LCPMs represents a promising platform for the treatment of vaginal candidiasis.

Sistemas precursores de cristais líquidos mucoadesivos para administração bucal de curcumina no tratamento do câncer bucal

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)