Data on statistical experimental design to formulate amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid for the treatment of vulvovaginal candidiasis.

Data described in this article are related to the research article entitled "Amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid (AMP EUD nanoparticles/HA) for the treatment of vulvovaginal candidiasis" [1]. In this work, we report original data on the statistical experimental design to formulate uncoated AMP EUD nanoparticles, data on the validation of spectrophotometric method to quantify the AMP released from uncoated EUD nanoparticles and coated with HA to obtain the in vitro drug release profiles as well as the drug encapsulation efficiency. In addition, we describe original data on characterization, including diameter size, polydispersity index, zeta potential, FTIR, DSC/TG, and XRD; data on diameter of in vitro inhibition halos of Candida albicans; and on the vaginal burden of infected animals treated with uncoated AMP EUD nanoparticles and AMP EUD nanoparticles/HA. Finally, different histological sections of endocervix collected from treated and untreated animals were inserted into this manuscript.

Brazilian green propolis modulates inflammation, angiogenesis and fibrogenesis in intraperitoneal implant in mice.

BACKGROUND: Chronic inflammatory processes in the peritoneal cavity develop as a result of ischemia, foreign body reaction, and trauma. Brazilian green propolis, a beeswax product, has been shown to exhibit multiple actions on inflammation and tissue repair. Our aim was to investigate the effects of this natural product on the inflammatory, angiogenic, and fibrogenic components of the peritoneal fibroproliferative tissue induced by a synthetic matrix. METHODS: Chronic inflammation was induced by placing polyether-polyurethane sponge discs in the abdominal cavity of anesthetized Swiss mice. Oral administration of propolis (500/mg/kg/day) by gavage started 24 hours after injury for four days. The effect of propolis on peritoneal permeability was evaluated through fluorescein diffusion rate 4 days post implantation. The effects of propolis on the inflammatory (myeloperoxidase and n-acetyl-ß-D-glucosaminidase activities and TNF-α levels), angiogenic (hemoglobin content-Hb), and fibrogenic (TGF-ß1 and collagen deposition) components of the fibrovascular tissue in the implants were determined 5 days after the injury. RESULTS: Propolis was able to decrease intraperitoneal permeability. The time taken for fluorescence to peak in the systemic circulation was 20±1 min in the treated group in contrast with 15±1 min in the control group. In addition, the treatment was shown to down-regulate angiogenesis (Hb content) and fibrosis by decreasing TGF-ß1 levels and collagen deposition in fibroproliferative tissue induced by the synthetic implants. Conversely, the treatment up-regulated inflammatory enzyme activities, TNF-α levels and gene expression of NOS2 and IFN-γ (23 and 7 fold, respectively), and of FIZZ1 and YM1 (8 and 2 fold) when compared with the untreated group. CONCLUSIONS: These observations show for the first time the effects of propolis modulating intraperitoneal inflammatory angiogenesis in mice and disclose important action mechanisms of the compound (downregulation of angiogenic components and activation of murine macrophage pathways).

Association of water extract of green propolis and liposomal meglumine antimoniate in the treatment of experimental visceral leishmaniasis.

This work investigated the use of water extract of green propolis (WEP) and its association with free or liposomal meglumine antimoniate (MA) for the treatment of murine visceral leishmaniasis. Mice infected with Leishmania infantum were treated with oral doses of WEP associated or not with a single dose of liposomal MA by intraperitoneal route. Parasite burden was assessed in the liver and spleen by limiting dilution assay, and alterations in the spleen cellular phenotype were evaluated by flow cytometry. Tissue damage was assessed by determination of biochemical markers of the liver, heart, and kidney function and histopathological analysis of the liver and spleen. Our data showed that treatment with WEP was able to reduce parasite load in the liver but not in the spleen. On the other hand, liposomal MA reduced parasite load in both organs. Unexpectedly, there was no synergism with the combination of WEP and liposomal MA in reducing the parasite load. The histopathological analysis showed that administration of WEP, liposomal MA, or their association was able to protect the liver and spleen from lesions caused by infection. No alteration in the profile of spleen cells by flow cytometry or in the liver, heart, and kidney functions by biochemical markers due to any of the treatments was observed. These results demonstrate that although WEP was able to significantly reduce the liver parasite load, its association with liposomal MA did not lead to significant improvement in reducing parasite load. On the other hand, treatment with WEP and/or liposomal MA protected the liver and spleen from lesions caused by the infection.

Ecto-nucleotidase activities of promastigotes from Leishmania (Viannia) braziliensis relates to parasite infectivity and disease clinical outcome.

BACKGROUND: Leishmania (Viannia) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions. Factors leading to this diversity of clinical presentations are not clear, but parasite factors have lately been recognized as important in determining disease progression. Given the fact that the activity of ecto-nucleotidases correlates with parasitism and the development of infection, we evaluated the activity of these enzymes in promastigotes from 23 L. braziliensis isolates as a possible parasite-related factor that could influence the clinical outcome of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Our results show that the isolates differ in their ability to hydrolyze adenine nucleotides. Furthermore, we observed a positive correlation between the time for peak of lesion development in C57BL/6J mice and enzymatic activity and clinical manifestation of the isolate. In addition, we found that L. (V.) braziliensis isolates obtained from mucosal lesions hydrolyze higher amounts of adenine nucleotides than isolates obtained from skin lesions. One isolate with high (PPS6m) and another with low (SSF) ecto-nucleotidase activity were chosen for further studies. Mice inoculated with PPS6m show delayed lesion development and present larger parasite loads than animals inoculated with the SSF isolate. In addition, PPS6m modulates the host immune response by inhibiting dendritic cell activation and NO production by activated J774 macrophages. Finally, we observed that the amastigote forms from PPS6m and SSF isolates present low enzymatic activity that does not interfere with NO production and parasite survival in macrophages. CONCLUSIONS/SIGNIFICANCE: Our data suggest that ecto-nucleotidases present on the promastigote forms of the parasite may interfere with the establishment of the immune response with consequent impaired ability to control parasite dissemination and this may be an important factor in determining the clinical outcome of leishmaniasis.

Local drug delivery system: inhibition of inflammatory angiogenesis in a murine sponge model by dexamethasone-loaded polyurethane implants.

Implants are defined as controlled sustained release delivery systems of therapeutic agents incorporated or dispersed into a polymeric carrier. These systems can be implanted in specific organs and delivered by the therapeutic agents at the target site to treat various pathological processes. In the present study, the effects of dexamethasone-loaded polyurethane implants [PU ACT (dexamethasone acetate) implants] on inflammatory angiogenesis in a murine sponge model were investigated. PU ACT implants were inserted into nonbiocompatible sponges, used as a framework for fibrovascular tissue growth, and implanted into subcutaneous tissue located on the back of mice. After 7 days of implantation, the implant system was collected and processed for the assessment of hemoglobin (Hb; vascular index), myeloperoxidase (MPO), and N-acetyl-ß-D-glucosaminidase (NAG; inflammatory enzymes activities) and collagen content. ACT released from the polymeric implants provided a significant decrease in the neovascularization in the sponge (Hb content). PU ACT implants provided no effects on neutrophil infiltration (MPO activity) but macrophage recruitment was affected by the glucocorticoid delivered by implants (NAG activity). ACT released from implants was able to reduce the collagen deposition. The qualitative histological findings corroborated with the measured biochemical parameters. These local drug delivery systems derived from polyurethane efficiently modulated the key components of inflammation, angiogenesis, and fibrosis induced by sponge discs in an experimental animal model.

Differential effects of rolipram on chronic subcutaneous inflammatory angiogenesis and on peritoneal adhesion in mice.

The specific PDE4 inhibitor (rolipram) has been shown to attenuate excessive accumulation/activation of inflammatory cells and fibroblasts and cytokine production in several pathological conditions through cyclic nucleotide modulation. Here, using the murine sponge model to induce chronic subcutaneous inflammatory response and to elicit the formation of intraperitoneal adhesions we explored the hypothesis that rolipram would exert beneficial effects on decreasing key components of both processes (inflammatory cell recruitment, angiogenesis, and deposition of extracellular matrix component). Two doses of rolipram (0.2 or 2 mg/kg/day) were administered orally for 7 days in groups of mice bearing either subcutaneous or intraperitoneal polyether-polyurethane implants. Rolipram was effective in inhibiting angiogenesis as assessed by hemoglobin content and VEGF levels in subcutaneous implants (about 40% with both doses) but failed to exert this activity in intraperitoneal implants. Conversely, accumulation of neutrophils and macrophages determined by measuring myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities intraimplant, respectively, was attenuated only in intraperitoneal implants by the treatment. Levels of TNF-alpha and MCP-1 were also determined and rolipram at both doses decreased the production of both cytokines in intraperitoneal implants. The levels of MCP-1 in the subcutaneous implants were not affected by the treatment. Fibrosis was evaluated by determining the amount of collagen and production of TGF-beta1 intraimplant. Both parameters were attenuated by rolipram. These results have shown differential sensitivity of proliferating tissues to PDE4 inhibitor indicating that this agent may be used to target inflammatory angiogenesis selectively.

Induction of apoptosis in tumor cells as a mechanism of tumor growth reduction in allergic mice.

Cancer is the leading cause of mortality worldwide. Analysis of epidemiological data has revealed a negative relationship between allergic conditions and cancer incidence. This study addresses the effects of chronic antigen ingestion by sensitized mice (allergy) on Ehrlich tumor growth in mouse footpad. Mice were sensitized (allergic) or not (sham) with ovalbumin and challenged orally with egg white solution. After one week of oral challenge, all mice were inoculated with experimental Ehrlich tumor (EET) cells in the footpad, and tumor growth was evaluated for 21 days. A decrease in tumor growth occurred, as assessed by paw thickness in the allergic group, which was associated with smaller areas of necrosis, reduced infiltration of neutrophils, and reduced levels of IFN-gamma, IL-4, and IL-10. Although, the tumor proliferation rate was similar in both groups, an increase in apoptosis occurred in allergic mice. In conclusion, analysis of the data obtained allows us to suggest that a concomitant allergic condition would reduce tumor progression through increased tumor cell apoptosis, accompanied by reduced areas of necrosis at the tumor site. Indeed, such findings suggested a possible mechanism for the reduced cancer incidence observed in allergic individuals.