Chemical Profiles and Cytotoxic Activities of Essential Oils from Six Species of Baccharis Subgenus Coridifoliae (Asteraceae).

Several Baccharis species are popularly known in traditional medicine as "carquejas", "vassouras", "ervas-santas" and "mio-mios", and are used as anti-inflammatories, digestives, and diuretics. This study aimed to investigate the chemical compositions and cytotoxic activities of essential oils (EOs) of six Baccharis species belonging to subgenus Coridifoliae, namely B. albilanosa, B. coridifolia, B. erigeroides, B. napaea, B. ochracea, and B. pluricapitulata. GC/MS analyses of the EOs showed that the oxygenated sesquiterpenes spathulenol (7.32-38.22 %) and caryophyllene oxide (10.83-16.75 %) were the major components for all the species. The EOs of almost all species were cytotoxic against cancer (BT-549, KB, SK-MEL and SK-OV-3) and normal kidney (VERO and LLC-PK1) cell lines, whereas B. erigeroides EO showed cytotoxicity only against LLC-PK1. This article augments the current knowledge about the chemical-biological properties of Baccharis subgenus Coridifoliae and discusses the therapeutic potentials of these economically unexploited plants.

Effect of an experimental desensitizing gel on bleaching-induced tooth sensitivity after in-office bleaching-a double-blind, randomized controlled trial.

OBJECTIVES: To evaluate the risk and intensity of tooth sensitivity (TS), and the efficacy of in-office bleaching after applying an experimental desensitizing gel composed of 10% calcium gluconate, 0.1% dexamethasone acetate, 10% potassium nitrate, and 5% glutaraldehyde. MATERIAL AND METHODS: In a split-mouth, double-blind, placebo-controlled study, 50 participants had their upper hemiarches randomized into experimental and placebo groups. Desensitizing and placebo gels were applied for 10 min before in-office bleaching (35% hydrogen peroxide, 1 × 50 min; two bleaching sessions; 1-week interval). TS was recorded immediately after bleaching, 1, 24, and 48 h after each session, with a 0-10 visual analogue scale (VAS) and a five-point numerical rating scale (NRS). The color was recorded in all groups at baseline, 1 week after each session, and 1 month after the end of bleaching using shade guide units (ΔSGUs) and a spectrophotometer (ΔEab, ΔE00, and ΔWID). RESULTS: Most participants (96%) felt some discomfort during treatment regardless of the study group. The odds ratio for pain was 0.65 (95% CI 0.1 to 4.1; p = 1.0). The intensity of TS did not differ between groups (p > 0.31), and it was only 0.34 VAS units lower in the experimental group. A significant color change occurred in both groups regardless of the group. CONCLUSIONS: The desensitizing experimental gel applied before in-office bleaching did not reduce the risk and the intensity of TS and did not affect color change. CLINICAL RELEVANCE: Although the experimental desensitizing agent with varying mechanisms of action did not jeopardize the color change, it did not reduce the risk or intensity of in-office bleaching. CLINICAL TRIAL REGISTRATION NUMBER: RBR-7T7D4D.

Assessment of the effect of experimental bleaching agent with nano-bioactive material on postoperative sensitivity: A randomized, triple blind clinical trial.

OBJECTIVES: This clinical study aimed to evaluate the effect of incorporating bioactive nanoparticles (n-Bm) inside an in-office bleaching gel on the risk and intensity of tooth sensitivity (TS) and on bleaching effectiveness. MATERIALS AND METHODS: Sixty-six participants were selected and randomly assigned into two groups: control-only in-office gel and experimental-in-office gel with n-Bm. Teeth were bleached in two sessions (3 × 15-min). TS was recorded using a VAS and NRS. The color change was evaluated by subjective (VITA Classical and VITA Bleachedguide) and objective (Easyshade spectrophotometer) methods at baseline and 30 days after the end of treatment. The TS was evaluated by McNemar, Wilcoxon Signed Rank, and paired t test. The color changes between groups were compared using paired t test (α = 0.05). RESULTS: No significant differences between the groups were observed in the risk (control = 27% [95%IC 18-39]; experimental = 21% [95%IC 13-32]) and intensity of TS, as well as in the color change (p >0.05) for any color measurement. CONCLUSION: The inclusion of n-Bm into the bleaching agents did not affect the whitening effectiveness, as well as the risk and intensity of TS between groups. However, the results of the absolute risk of TS were low for both in-office gels used. CLINICAL SIGNIFICANCE: Despite no significant differences between groups, both experimental bleaching agents present suitable results with low values for TS.

Effect of topical application of nanoencapsulated eugenol on dental sensitivity reduction after in-office dental bleaching: a randomized, triple-blind clinical trial.

PURPOSE: This randomized, split-mouth, triple-blind clinical study evaluated the effect of application of nanoencapsulated eugenol (NE) on the absolute risk and intensity of tooth sensitivity (TS) resulting from in-office bleaching. METHODS: Fifty-six patients received a NE in one hemiarch and a placebo gel in the other hemiarch, determined by random sequence, before in-office bleaching. A visual analogue scale (VAS) (0-10) and a numeric rating scale (NRS) (0-4) were used to record TS during bleaching and 1 and 48 h after bleaching. The tooth color was performed from baseline to 2 weeks after bleaching with shade guides (ΔSGU) and a spectrophotometer (∆Eab , ∆E00, and WID ). The TS was assessed through the McNemar test (α = 0.05) and by the Wilcoxon signed-rank test (NRS) and paired t-test (VAS). The paired test-t was employed to compare the color changes (ΔSGU and ΔEab , ∆E00, and WID ). The significance level was 5%. RESULTS: No statistically significant difference was found in the absolute risk or intensity of TS between both groups (p > 0.05). A significant color change was observed in both groups (p > 0.05). CONCLUSION: Administration of the gel containing NE before the in-office dental bleaching did not reduce the TS and did not interfere in the bleaching effect. CLINICAL RELEVANCE STATEMENT: The use of desensitizing gel containing NE did not reduce in-office bleaching-induced tooth sensitivity.

Ethylcellulose microparticles enhance 3,3'-diindolylmethane anti-hypernociceptive action in an animal model of acute inflammatory pain.

AIM: The present work aimed at the DIM-loaded microparticles development and anti-hypernociceptive action evaluation. METHOD: The formulations were prepared by O/W solvent emulsion-evaporation method and characterised by particle diameter, content and DIM encapsulation efficiency, drug release profile, thermal behaviour and physicochemical state. The anti-hypernociceptive action was evaluated in the animal model of acute inflammatory pain. RESULT: The MPs had a mean diameter in the micrometric range (368 ± 31 µm), narrow size distribution, DIM content of 150 mg/g, encapsulation efficiency around 84% and prolonged compound release. Evaluations of the association form of DIM to MPs demonstrated the feasibility of the systems to incorporate DIM and increases its thermal stability. An improvement in the anti-hypernociceptive action of DIM was observed by its microencapsuation, because it was increased and prolonged. CONCLUSION: Therefore, the MPs developed represent a promising formulation for oral administration of the DIM in the treatment of inflammatory pain.

Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells.

Background: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and/or methotrexate were prepared by an interfacial deposition of preformed polymer method. Methods: Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. Results: The colloidal suspensions of nanocapsules showed suitable size (287 to 325 nm), negative charge (-33 to -41 mV) and high encapsulation efficiency (82.4 to 99.4%). Spherical particles at nanoscale dimensions were observed by scanning electron microscopy. X-ray diffraction analysis indicated that nanocapsules exhibited a non-crystalline pattern with a remarkable decrease of crystalline peaks of the raw materials. Fourier-transform infrared spectra demonstrated no chemical bond between the drug(s) and polymers. Drug release experiments evidenced a controlled release pattern with no burst effect for nanocapsules containing curcumin and/or methotrexate. The nanoformulation containing curcumin and methotrexate (NCUR/MTX-2) statistically decreased the cell viability of Calu-3. The fluorescence and morphological analyses presented a predominance of early apoptosis and late apoptosis as the main death mechanisms for Calu-3. Conclusions: Curcumin and methotrexate co-loaded nanocapsules can be further used as a novel therapeutic strategy for treating non-small-cell lung cancer.

Design of Pegylated-Nanocapsules to Diphenyl Diselenide Administration: In Vitro Evidence of Hemocompatible and Selective Antiglioma Formulation.

Diphenyl diselenide [(PhSe)2] is a pleiotropic pharmacological agent, but it has low aqueous solubility. The nanoencapsulation of (PhSe)2 allowed the preparation of an aqueous formulation as well as potentiated its in vitro antitumor effect and the effectiveness in a preclinical model of glioblastoma when administered by the intragastric route. Thus, aiming at maximizing the therapeutic potential of (PhSe)2, the present study designed a pegylated-formulation intending to intravenous administration of the (PhSe)2 as a new approach for glioma therapy. The poly(Ɛ-caprolactone) nanocapsules containing (PhSe)2 were physically coated with polyethyleneglycol (PEG) using the preformed polymer interfacial deposition technique and evaluated through physicochemical, morphological, spectroscopic, and thermal characteristics. Hemocompatibility was determined by the in vitro hemolysis test and cytotoxicity assays were performed in astrocytes and glioma C6 cells (10-100 µM). The pegylated-nanocapsules had an average diameter of 218 ± 25 nm, polydispersity index of 0.164 ± 0.046, zeta potential of - 8.1 ± 1.6 mV, pH 6.0 ± 0.09, (PhSe)2 content of 102.00 ± 3.57%, and encapsulation efficiency around 98%. Besides, the (PhSe)2 pegylated-nanocapsules were spherical, presented absence of chemical interaction among the constituents, and showed higher thermal stability than the non-encapsulated materials. PEG-coated nanocapsules did not cause hemolytic effect while formulations without PEG induced a hemolysis rate above 10%. Moreover, pegylated-nanocapsules had superior in vitro antiglioma effect in comparison to free compound (IC50: 24.10 µM and 74.83 µM, respectively). Therefore, the (PhSe)2-loaded pegylated-nanocapsule suspensions can be considered a hemocompatible formulation for the glioma treatment by the intravenous route.

Prior Application of 10% Potassium Nitrate to Reduce Postbleaching Sensitivity: A Randomized Triple-Blind Clinical Trial.

OBJECTIVE: To evaluate if the topical application of 10% potassium nitrate applied before in-office bleaching is effective to reduce the risk and intensity of tooth sensitivity (TS), as well as to evaluate if its application can jeopardize color change. MATERIALS AND METHODS: A randomized, split-mouth triple-blind clinical trial was conducted on 43 young patients with incisors A2 or darker. Half of the patient's upper arch received either the application of a 10% potassium nitrate or placebo gel for 10 min in a university setting. In-office bleaching was performed in three 15-min applications in two clinical sessions (1-week interval) using 35% hydrogen peroxide. Risk and intensity of TS was recorded with a 0-4 Numeric Rating Scale and a 0-10 Visual Analogue Scale during bleaching, 1 hour, 24 hours, and 48 hours after bleaching. Color was evaluated before and 1 month after bleaching with shade guides (Vita Classical and Vita Bleachedguide) and a spectrophotometer. The risk of TS (McNemar's test) and intensity of TS (Wilcoxon signed-rank for Numeric Rating Scale and paired t-test for Visual Analogue Scale) were statistically evaluated. Color change was compared using paired t-test. Significant level was set at 5%. RESULTS: No significant difference was observed in the absolute risks of TS between groups (RR = 1.11; 95% CI 0.97 to 1.27; P = .12), which exceeded 87% for both groups. Similarly, no difference in TS intensities was detected (P > .05). Significant whitening was observed with all color measurement instruments with no difference between groups (P > .05). CONCLUSION: The topical application of 10% potassium nitrate, before in-office bleaching, did not reduce the risk and intensity of TS and did not jeopardize color change.

Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers, in vitro dissolution, antioxidant potential and in vivo anti-platelet effect.

This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100%, whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which denoted intermolecular O-H•••O = C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect.

Potential of desensitizing toothpastes to reduce the hydrogen peroxide diffusion in teeth with cervical lesions.

PURPOSE: To evaluate the occlusive potential of four toothpastes by atomic force microscopy (AFM) before and after bleaching and quantify the hydrogen peroxide (HP) diffusion into the pulp chamber after application of desensitizing toothpastes in teeth with cervical lesions. METHODS: In 52 human extracted premolars, 2-mm deep artificial cervical lesions (ACL) were prepared and rinsed with EDTA for 10 seconds. Then teeth were adapted in a brushing machine and brushed with one of the following toothpastes [Regular toothpaste with no occlusive compounds Colgate Cavity Protection (CP), Oral-B Pro Health (OB), Colgate ProRelief (PR) and Sensodyne Rapid Relief (RR)] under constant loading (250 g; 4.5 cycles/seconds; 3 minutes). In 13 teeth (control group), no artificial cervical lesion was prepared. After that, the teeth were bleached with 35% HP with three 15-minute applications. The HP diffusion was measured spectrophotometrically as a stable red product based on HP reaction with 4-aminoanthipyrine and phenol in presence of peroxidase, at a wavelength of 510 nm and the dentin surfaces of ACL were evaluated before and after bleaching by AFM. Data was statistically analyzed by one-way ANOVA and Tukey's test (alpha = 0.05). RESULTS: In the AFM images, some modifications of the dentin surface were observed after application of OB and RR. However, only for RR the formation of a surface deposit was produced, which occluded the majority of the dentin tubules. Also, only for RR, this deposit was not modified/removed by bleaching. Despite this, all groups with ACL showed higher HP penetration than sound teeth, regardless of the toothpaste used (P < 0.001).

Beclomethasone Dipropionate-Loaded Polymeric Nanocapsules: Development, In Vitro Cytotoxicity, and In Vivo Evaluation of Acute Lung Injury.

The aim of this work was to develop polymeric nanocapsules intended for the pulmonary delivery of beclomethasone dipropionate using ethyl cellulose or poly(ε-caprolactone). The formulations showed adequate physicochemical characteristics, namely, average diameter lower than 260 nm, low polydispersity index (< 0.2), negative zeta potential, neutral pH values, and encapsulation efficiencies close to 100%. The thermal analysis by DSC suggested that beclomethasone dipropionate encapsulated in the nanocapsules was in an amorphous state. In addition, both ethyl cellulose and poly(ε-caprolactone) nanocapsules were able to delay the drug photodegradation under UVC radiation. The in vitro drug release showed a prolonged release without burst effect using the dialysis bag diffusion technique. Moreover, ethyl cellulose and poly(ε-caprolactone) nanocapsules presented low in vitro cytotoxicity on 3T3 fibroblasts cells. In vivo, the formulations showed no acute pulmonary injury in rats. Therefore, the developed nanocapsules could be considered suitable carriers to be used for beclomethasone dipropionate pulmonary delivery.

PCL/PHBV microparticles as innovative carriers for oral controlled release of manidipine dihydrochloride.

Microparticles of poly(ε-caprolactone) (PCL) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) containing manidipine dihydrochloride (MAN) were successfully prepared by the simple emulsion/solvent evaporation method. All formulations showed loading efficiency rates greater than 80% and average particle size less than 8 µm. Formulations had spherical shape with smooth and porous surface for PCL and PHBV, respectively. According to Fourier-transform infrared spectroscopy, initial components were not chemically modified during microencapsulation. X-ray diffraction patterns and differential scanning calorimetry demonstrated that this process led to drug amorphization. In vitro dissolution studies showed that all microparticles prolonged MAN release, mainly which one obtained using PCL that contained 5% of drug loaded (PCL-M5). Animal studies demonstrated that formulation PCL-M5 was able to keep the variation of mean arterial pressure after phenylephrine administration up to 24 hours. These data confirmed the sustained antihypertensive effect of the investigated microparticles. Results provided an experimental basis for using formulation PCL-M5 as a feasible carrier for oral controlled release of MAN intended for treating high blood pressure.

Effect of a novel quaternary ammonium methacrylate polymer (QAMP) on adhesion and antibacterial properties of dental adhesives.

This study investigated the resin-dentin bond strength (µTBS), degree of conversion (DC), and antibacterial potential of an innovative adhesive system containing a quaternary ammonium methacrylate polymer (QAMP) using in situ and in vitro assays. Forty-two human third molars were flattened until the dentin was exposed and were randomly distributed into three groups of self-etching adhesive systems: Clearfil™ SE Bond containing 5% QAMP (experimental group), Clearfil™ Protect Bond (positive control) and Clearfil™ SE Bond (negative control). After light curing, three 1 mm-increments of composite resin were bonded to each dentin surface. A total of thirty of these bonded teeth (10 teeth per group) was sectioned to obtain stick-shaped specimens and tested under tensile stress immediately, and after 6 and 12 months of storage in distilled water. Twelve bonded teeth (4 teeth per group) were longitudinally sectioned in a mesio-to-distal direction to obtain resin-bonded dentin slabs. In situ DC was evaluated by micro-Raman spectroscopy. In vitro DC of thin films of each adhesive system was measured using Fourier transform infrared spectroscopy. In vitro susceptibility tests of these three adhesive systems were performed by the minimum inhibitory/minimum bactericidal concentration (MIC/MBC) assays against Streptococcus mutans, Lactobacillus casei, and Actinomyces naeslundii. No statistically significant difference in µTBS was observed between Clearfil™ SE Bond containing 5% QAMP and Clearfil™ SE Bond (p>0.05) immediately, and after 6 and 12 months of water storage. However Clearfil™ Protect Bond showed a significant reduction of µTBS after 12 months of storage (p=0.039). In addition, QAMP provided no significant change in DC after incorporating into Clearfil™ SE Bond (p>0.05). Clearfil™ SE Bond containing 5% QAMP demonstrated MIC/MBC values similar to the positive control against L. casei and A. naeslundii and higher than the negative control for all evaluated bacterial strains. The use of QAMP in an adhesive system demonstrated effective bond strength, a suitable degree of conversion, and adequate antibacterial effects against oral bacteria, and may be useful as a new approach to provide long-lasting results for dental adhesives.

New intracanal formulations containing doxycycline or chlorhexidine against Enterococcus faecalis.

The present study aims to evaluate the antimicrobial effect of two new intracanal preparations against E. faecalis. Thirty single-rooted human canine teeth were used. The crowns were removed and the roots were instrumented using a conventional technique. Three groups of ten teeth each were infected with 108 CFU/ ml of E. faecalis for 21 days. The root canals were flled with new intracanal medications containing 3% doxycycline hydrochloride (DX) or 2% chlorhexidine digluconate (CHX). Ten teeth received no medication (NM)-negative control. Microbial samples were obtained 21 days after contamination: 14 days under the effect of the intracanal medications and 7 days after replacing the medications by BHI broth. The samples were homogenized, diluted, seeded on BHI agar and incubated for 48h/36°C. The number of colony forming units (CFU/ml) was obtained and analyzed statistically. All intracanal dressings significantly reduced the number of bacterial cells in the root canal after 14 days with medication. After the period with 7 days with BHI broth, the CFU counts of E. faecalis remained at low values. However, the NM group showed a significant increase of CFU in this period to similar values of the initial contamination. 3% doxycycline hydrochloride gel and 2% CHX gel were effective to eliminate E. faecalis from the root canal system.

Effect of topical application of ibuprofen/arginine on the in-office bleaching-induced tooth sensitivity: A randomized, triple-blind controlled trial.

OBJECTIVE: The application of anti-inflammatories as topical desensitizers before dental bleaching is an approach to reduce bleaching-induced tooth sensitivity (TS). This randomized controlled trial compared the risk and intensity of TS and the color change resulting from in-office dental bleaching after using an experimental desensitizing gel containing ibuprofen and arginine. METHODS: Sixty-two participants with upper canine shades A2 or darker were randomly assigned to either the ibuprofen-arginine desensitizing group or the placebo group. The desensitizing gel was applied for 15 min before in-office bleaching with 35 % hydrogen peroxide gel for 50 min (2 sessions). To assess the absolute risk and intensity of TS, visual (0-10) and numeric rating (0-5) scales were used, and group comparisons were made using the McNemar test, Wilcoxon test, and paired Student t-test (α = 0.05). Color change was evaluated using Vita Classical, Vita Bleachedguide (ΔSGU), and Vita EasyShade (ΔEab, ΔE00, and ΔWID) before and one month after the bleaching procedure. Group comparisons for color change were done using a paired t-test (α = 0.05). RESULTS: The odds ratio for TS was 0.14 [95 % CI 0.02 to 0.6], meaning lower odds of TS for the desensitizing gel. A lower intensity of TS was also observed for the experimental group (p < 0.005) up to 48 h after bleaching. All color evaluation tools demonstrated effective and similar whitening for both groups (p > 0.05). CONCLUSIONS: Using the experimental desensitizing gel containing ibuprofen and arginine effectively reduced the risk and intensity of TS without compromising the bleaching efficacy. CLINICAL RELEVANCE: The topical application of ibuprofen/arginine on the in-office bleaching reduced risk and intensity of bleaching-induced tooth sensitivity.

Acute toxicity and genotoxicity of Schinus molle L. aqueous extract/ethanol-soluble fraction in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus molle L. is a medicinal species belonging to the Anacardiaceae family. It is commonly referred to as "aroeira" and its leaves and roots are utilized for treating different pathological conditions. However, despite its widespread use in traditional medicine, there is a lack of in-depth toxicological studies. AIM: To evaluate the acute toxicity and genotoxicity of S. molle aqueous extract/ethanol-soluble fraction in rats. MATERIAL AND METHODS: First, a purified aqueous extract was obtained from the leaves of S. mole through infusion (referred to as EESM) and its compounds were identified using LC-DAD-MS data. Female rats were then subjected to acute oral toxicity tests using doses of 5, 50, 300, and 2000 mg/kg of ESSM. Studies on genetic material, including the micronucleus test and comet assay, were conducted on male and female Wistar rats using the same doses as in the acute toxicity test. For both assays, ESSM was administered orally. RESULTS: The main metabolites annotated from ESSM were dimeric proanthocyanidins, phenylpropanoids acids, flavan-3-ols, simple organic acids (C6-C1), a flavonol di-O-glycosylated (rutin), and O-glycosylated megastigmane. The ESSM did not exhibit any acute toxic effects, such as changes in biochemical, hematologic, or histopathological analysis. Furthermore, no changes were observed in comet assay or micronucleus tests when rats were given doses of 5, 50, 300, or 2000 mg/kg of ESSM. CONCLUSION: The results showed that the ESSM does not induce acute toxicity or exhibit genotoxicity up to a dose of 2000 mg/kg.

Computational simulation on the study of Tacrolimus and its improved dermal retention using Poly(Ԑ-caprolactone) nanocapsules.

Tacrolimus (TAC) is a drug from natural origin that can be used for topical application to control autoimmune skin diseases such as atopic dermatitis, psoriasis, and vitiligo. Computational simulation based on quantum mechanics theory by solving Schrödinger Equation for n-body problem may allow the theoretical calculation of drug geometry, charge distribution and dipole moment, electronic levels and molecular orbitals, electronic transitions, and vibrational transitions. Additionally, the development of novel nanotechnology-based delivery systems containing TAC can be an approach for reducing the dose applied topically, increasing dermal retention, and reducing the reported side effects due to the controlled release pattern. Firstly, this paper was devoted to obtaining the molecular, electronic, and vibrational data for TAC by using five semi-empirical (SE) methods and one Density Functional Theory (DFT) method in order to expand the knowledge about the drug properties by computational simulation. Then, this study was carried out to prepare TAC-loaded poly(ԑ-caprolactone) nanocapsules by interfacial polymer deposition following solvent displacement and investigate the in vitro drug permeation using the Franz diffusion cell and the photoacoustic spectroscopy. Computational simulations were compared in the three schemes SE/SE, SE/DFT, and DFT/DFT, where the first method represented the procedure used for geometry optimization and the second one was performed to extract electronic and vibrational properties. Computational data showed correspondence with TAC geometry description and electronic properties, with few differences in HOMO - LUMO gap (Δ) and dipole values. The SE/DFT and DFT/DFT methods presented a better drug description for the UV-Vis, Infrared, and Raman spectra with low deviation from experimental values. Franz cell model demonstrated that TAC was more delivered across the Strat-M® membrane from the solution than the drug-loaded poly(ԑ-caprolactone) nanocapsules. Photoacoustic spectroscopy assay revealed that these nanocapsules remained more retained into the Strat-M® membranes, which is desirable for the topical application.

Characterization, Antifungal Evaluation against Candida spp. Strains and Application of Nystatin: ß-cyclodextrin Inclusion Complexes.

BACKGROUND: Nystatin (Nys) is a fungicidal drug commonly prescribed for candidiasis disease in several administration routes. However, Nys is a class IV drug, according to the Biopharmaceutical Classification System, that possesses limited bioavailability and is used for local activity. OBJECTIVE: This study developed and characterized nystatin:ß-cyclodextrin (Nys:ßCD) inclusion complexes and evaluated their activity against Candida spp. METHODS: Complexes were characterized by physicochemical techniques and drug dissolution profiles. The susceptibility of C. albicans, C. krusei, C. parapsilosis, C. glabrata, C. guilliermondii, C. tropicalis, and C. auris was assessed using the broth microdilution method. The applicability of Nys:ßCD inclusion complex was evaluated by incorporating it into a temporary soft material for denture stomatitis treatment. RESULTS: Nys was better complexed in a 1:1 molar ratio by freeze-drying and spray-drying methods. The inclusion complexes show bi-exponential release, an initial burst release followed by a sustained manner, presenting higher dissolution efficiency than raw Nys. The 1:1 freeze-drying Nys:ßCD complex presents antifungal activity against all evaluated Candida strains, showing the maintenance of the drug effectiveness. The inclusion complex incorporated into a tissue conditioner material for denture stomatitis treatment effectively inhibited more than 90% of C. albicans biofilm growth during 7 and 14 days, in a half dose compared to raw Nys. CONCLUSION: This work represents a significant contribution to treating a wide variety of diseases caused by the Candida species, optimizing the drug bioavailability and compliance to the treatment due to improved drug solubility, dissolution, and sustained delivery.

Preclinical Trial of Ocotea puberula (Rich.) Nees ("Canela-Guaicá") in Wound Healing: Validation of a Traditional Medicine Practice Used by Indigenous Groups in Southern Brazil.

Background: "Canela-guaicá," "guaicá," or "canela-sebo" [Ocotea puberula (Rich.) Nees] is a native species that is traditionally used by Kaingang indigenous groups for wound healing in southern Brazil. The aim of this study was to extract the mucilage from O. puberula barks, perform its phytochemical and physicochemical characterization, and investigate its healing potential. Methods: A murine wound model was used as a preclinical trial for authentication of the traditional knowledge from Kaingang indigenous communities. Results: Alkaloids and polysaccharides were identified by usual qualitative reactions and Fourier-transform infrared spectroscopy. This natural product showed thermal stability and pseudoplastic properties that were considered suitable for the intended use. A higher initial exacerbation of inflammatory response after 7 days, an improved angiogenesis after 14 days, and an increased wound shrinkage after 21 days were statistically significant for the "canela-guaicá" bark extract in the preclinical trial when compared to the silver calcium alginate dressing (positive control). Conclusion: The healing potential of the "canela-guaicá" bark extract, traditionally used by the Kaingang indigenous community from southern Brazil, was preclinically validated. This study paves the way for designing novel wound dressings containing this natural product in order to treat acute and chronic wounds.

Characterization and antifungal activity of chlorhexidine:ß-cyclodextrin inclusion complexes.

Aim: This study aimed to develop, characterize and analyze the antifungal activity of chlorhexidine:ß-cyclodextrin inclusion complexes (Chx:ßCD). Materials & methods: Chx:ßCD were characterized by physicochemical techniques and the susceptibility of nine Candida strains was assessed. The inhibition of Candida albicans biofilm growth was evaluated in a denture material modified with the incorporation of Chx:ßCD. Results: Chx was better complexed in 1:2 molar ratio by freeze-drying. Chx:ßCD presented antifungal activity against all Candida strains. When incorporated into the denture material, Chx:ßCD showed better antifungal activity, as it required about 7.5% of Chx concentration compared with the raw Chx for 14 days. Conclusion: The improved characteristics of Chx:ßCD can result in new formulations to treat oral candidiasis and denture stomatitis.

Many people who wear dentures can get a fungal infection called denture stomatitis. Treating this infection is hard because it often comes back. There are many reasons why it can come back, like not following instructions, taking the wrong amount of medicine or having a bad reaction to the drugs. Using old and poorly fitting dentures and the difficulty to maintain the medicine in the right place can also make it harder to get better. One idea to make treatment easier is to add stronger drugs with fewer side effects to the material used to make dentures. That way, patients would only need to wear dentures with the right amount of medicine for a certain time to treat the infection.