Sávio M.L. Gontijo

Development of Sulfadiazine-Decorated PLGA Nanoparticles Loaded with 5-Fluorouracil and Cell Viability

The aim of this work was to synthesize sulfadiazine-poly(lactide-co-glycolide) (SUL-PLGA) nanoparticles (NPs) for the efficient delivery of 5-fluorouracil to cancer cells. The SUL-PLGA conjugation was assessed using FTIR, 1H-NMR, 13C-NMR, elemental analysis and TG and DTA analysis. The SUL-PLGA NPs were characterized using transmission and scanning electron microscopy and dynamic light scattering. Additionally, the zeta potential, drug content, and in vitro 5-FU release were evaluated. We found that for the SUL-PLGA NPs, Dh = 114.0 nm, ZP = −32.1 mV and the encapsulation efficiency was 49%. The 5-FU was released for up to 7 days from the NPs. Cytotoxicity evaluations of 5-FU-loaded NPs (5-FU-SUL-PLGA and 5-FU-PLGA) on two cancer cell lines (Caco-2, A431) and two normal cell lines (fibroblast, osteoblast) were compared. Higher cytotoxicity of 5-FU-SUL-PLGA NPs were found to both cancer cell lines when compared to normal cell lines, demonstrating that the presence of SUL could significantly enhance the cytotoxicity of the 5-FU-SUL-PLGA NPs when compared with 5-FU-PLGA NPs. Thus, the development of 5-FU-SUL-PLGA NPs to cancer cells is a promising strategy for the 5-FU antitumor formulation in the future.

PLGA nanofibers improves the antitumoral effect of daunorubicin.

The objective of this study was to evaluate the in vivo anti-inflammatory angiogenesis activity and in vitro cytotoxicity on normal and cancer cell models of a drug delivery system consisting of poly(lactic-co-glycolic acid) nanofibers loaded with daunorubicin (PLGA-DNR) that were fabricated using an electrospinning process. The PLGA-DNR nanofibers were also characterized by thermogravimetric analysis (TGA), differential thermal analysis (DTA) and differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and confocal fluorescence microscopy. In vitro release of DNR from the nanofibers and its corresponding mechanism were also evaluated. Sixty-five percent of the DNR was released in an initial burst over 8h, and by 1224 h, eighty-five percent of the DNR had been released. The Higuchi model yielded the best fit to the DNR release profile over the first 8h, and the corresponding data from 24 to 1224 h could be modeled using zero-order kinetics. The PLGA-DNR nanofibers exhibited a higher cytotoxicity to A431 cells than free DNR but a cytotoxicity similar to free DNR against fibroblast cells. A higher antiangiogenic effect of PLGA nanofibers was observed in the in vivo data when compared to free DNR, and no inflammatory potential was observed for the nanofibers.

Structural and thermodynamic characterization of doxycycline/β-cyclodextrin supramolecular complex and its bacterial membrane interactions.

Doxycycline is a semi-synthetic antibiotic commonly used for the treatment of many aerobic and anaerobic bacteria. It inhibits the activity of matrix metalloproteinases (MMPs) and affects cell proliferation. In this study, the structural and thermodynamic parameters of free DOX and a DOX/βCD complex were investigated, as well as their interactions and effects on Staphylococcus aureus cells and cellular cytotoxicity. Complexation of DOX and βCD was confirmed to be an enthalpy- and entropy-driven process, and a low equilibrium constant was obtained. Treatment of S. aureus with higher concentrations of DOX or DOX/βCD resulted in an exponential decrease in S. aureus cell size, as well as a gradual neutralization of zeta potential. These thermodynamic profiles suggest that ion-pairing and hydrogen bonding interactions occur between DOX and the membrane of S. aureus. In addition, the adhesion of βCD to the cell membrane via hydrogen bonding is hypothesized to mediate a synergistic effect which accounts for the higher activity of DOX/βCD against S. aureus compared to pure DOX. Lower cytotoxicity and induction of osteoblast proliferation was also associated with DOX/βCD compared with free DOX. These promising findings demonstrate the potential for DOX/βCD to mediate antimicrobial activity at lower concentrations, and provides a strategy for the development of other antimicrobial formulations.

Nanofibers containing tetracycline/β-cyclodextrin: Physico-chemical characterization and antimicrobial evaluation

This study aimed to compare two nanofiber drug delivery systems that were prepared with an electrospun process and have the potential to serve as adjuvants for the treatment of periodontal disease. The first system was composed of polycaprolactone loaded with tetracycline (TCN) and the second was composed of polycaprolactone loaded with tetracycline/β-cyclodextrin (TCN:BCD). An antimicrobial diffusion test was performed for each of these sets of nanofibers with the microorganisms, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, both of which contribute to periodontal disease. In vitro release profiles were also obtained, and the nanofibers were characterized by thermal analysis, x-ray powder diffraction, infrared absorption spectroscopy, and scanning electron microscopy. Profiles of the TCN and TCN:BCD nanofibers showed that drug release occurred for up to 14days. However, the TCN:BCD nanofibers appeared to better protect and enhance the biological absorption of TCN due to the formation of a TCN:BCD inclusion complex.

Development of a Calcium Phosphate Nanocomposite for Fast Fluorogenic Detection of Bacteria

Current procedures for the detection and identification of bacterial infections are laborious, time-consuming, and require a high workload and well-equipped laboratories. Therefore the work presented herein developed a simple, fast, and low cost method for bacterial detection based on hydroxyapatite nanoparticles with a nutritive mixture and the fluorogenic substrate. Calcium phosphate ceramic nanoparticles were characterized and integrated with a nutritive mixture for the early detection of bacteria by visual as well as fluorescence spectroscopy techniques. The composite was obtained by combining calcium phosphate nanoparticles (Ca:P ratio, 1.33:1) with a nutritive mixture of protein hydrolysates and carbon sources, which promote fast bacterial multiplication, and the fluorogenic substrate 4-methylumbellipheryl-β-d-glucuronide (MUG). The composite had an average particle size of 173.2 nm and did not show antibacterial activity against Gram-negative or Gram-positive bacteria. After an Escherichia coli suspension was in contact with the composite for 60–90 min, fluorescence detected under UV light or by fluorescence spectrophotometer indicated the presence of bacteria. Intense fluorescence was observed after incubation for a maximum of 90 min. Thus, this calcium phosphate nanocomposite system may be useful as a model for the development of other nanoparticle composites for detection of early bacterial adhesion.

Sub-additive effects of photodynamic therapy combined with erlotinib for the treatment of epidermoid carcinoma: An in vitro study

BACKGROUND Photodynamic therapy (PDT) is an antitumour treatment that employs the combination of a photosensitive compound, oxygen and visible light. To improve the antitumour activity of PDT, the present study used the strategy of combining PDT with erlotinib (ERL), a drug frequently used in the treatment of epidermoid carcinoma. METHODS An MTT cell viability assay was used to evaluate the cytotoxicity of PDT combined with ERL on A431 epidermoid carcinoma cells in vitro. This study evaluated the cytotoxicity of the following treatments: red laser irradiation (660nm) at different power densities (1.25-180J/cm2), the photosensitizer methylene blue (MB) at concentrations of 0.39-100μM, PDT (12.5μM MB and laser power densities from 1.25 to 180J/cm2), and PDT (12.5μM MB and a laser density of 120J/cm2) plus ERL (1μM). RESULTS The laser power densities that were tested showed no cytotoxicity in A431 cells. MB showed a dose-dependent cytotoxicity. In PDT, an increase in the dose of light resulted in an increase in the cytotoxicity of MB. In addition, there was a sub-additive effect between PDT and ERL compared to the effect of each therapy alone. CONCLUSIONS The sub-additive effect between PDT and ERL suggests that their combination may be an important strategy in the treatment of epidermoid carcinoma.

Chemical composition and antifungal and anticancer activities of extracts and essential oils of Schinus terebinthifolius Raddi fruit

In this study, we isolated and characterized dichloromethane and hexane extracts, complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD), of Schinus terebinthifolius fruits. Such complexation may be useful in the formulation of herbal medicines, by improving solubility, or increasing stability by reducing the loss of volatile compounds. The cytotoxicity in osteoblasts, antifungal against Malassezia furfur and antitumor activities were evaluated in Caco-2 cells. The antifungal activity of the extracts and the essential oil in natura or complexed with HP-β-CD against the fungus M. furfur was evaluated by agar diffusion methods and quantitatively by inhibitory concentration (IC). All samples inhibited fungus growth and, when complexed with HP-β-CD, the IC was reduced by 50%. Osteoblast cell viability was not affected by the presence of extracts and oil. The antitumor activity of the extract in dichloromethane was evaluated using Caco-2 cells. The results demonstrated significant reduction in cell viability in the presence of the extract, which makes it a promising candidate for cancer treatment.

Hyperthermia-mediated drug delivery induces biological effects at the tumor and molecular levels that improve cisplatin efficacy in triple negative breast cancer

ABSTRACT Triple negative breast cancer is an aggressive disease that accounts for at least 15% of breast cancer diagnoses, and a disproportionately high percentage of breast cancer related morbidity. Intensive research efforts are focused on the development of more efficacious treatments for this disease, for which therapeutic options remain limited. The high incidence of mutations in key DNA repair pathways in triple negative breast cancer results in increased sensitivity to DNA damaging agents, such as platinum‐based chemotherapies. Hyperthermia has been successfully used in breast cancer treatment to sensitize tumors to radiation therapy and chemotherapy. It has also been used as a mechanism to trigger drug release from thermosensitive liposomes. In this study, mild hyperthermia is used to trigger release of cisplatin from thermosensitive liposomes in the vasculature of human triple negative breast cancer tumors implanted orthotopically in mice. This heat‐triggered liposomal formulation of cisplatin resulted in significantly delayed tumor growth and improved overall survival compared to treatment with either non‐thermosensitive liposomes containing cisplatin or free cisplatin, as was observed in two independent tumor models (i.e. MDA‐MB‐231 and MDA‐MB‐436). The in vitro sensitivity of the cell lines to cisplatin and hyperthermia alone and in combination was characterized extensively using enzymatic assays, clonogenic assays, and spheroid growth assays. Evaluation of correlations between the in vitro and in vivo results served to identify the in vitro approach that is most predictive of the effects of hyperthermia in vivo. Relative expression of several heat shock proteins and the DNA damage repair protein BRCA1 were assayed at baseline and in response to hyperthermia both in vitro and in vivo. Interestingly, delivery of cisplatin in thermosensitive liposomes in combination with hyperthermia resulted in the most significant tumor growth delay, relative to free cisplatin, in the less cisplatin‐sensitive cell line (i.e. MDA‐MB‐231). This work demonstrates that thermosensitive cisplatin liposomes used in combination with hyperthermia offer a novel method for effective treatment of triple negative breast cancer. Graphical abstract Figure. No Caption available.

Treatment of denture stomatitis: literature review

Objective: this study aimed to investigate the main therapeutic options for denture stomatitis in patients using complete removable prostheses, to determine the best treatment method, avoiding relapses and improving patients’ quality of life. Material and Methods: a search was made in the databases and electronic search tools PubMed, LILACS, SciELO and Web of Science using keywords, in Portuguese and English, such as denture stomatitis, Candida albicans, antifungal, oral candidiasis, and treatment. Results: studies have shown that the main drugs used in the treatment of denture stomatitis are miconazole, fluconazole, itraconazole, nystatin, amphotericin B, ketoconazole, clotrimazole and chlorhexidine. Regardless of the treatment employed, there is an improvement in the disease’s clinical symptoms, but it does not prevent recolonization of the oral mucosa in patients with poor hygiene of the dental prosthesis. Conclusion: it is not possible to determine the best therapy for denture stomatitis, since the studies evaluated showed drug efficacy, but with relapses, especially in patients with poor hygiene of the dental prosthesis.