Cilostazol protects against changes caused by streptozotocin-induced diabetic retinopathy / Cilostazol protege contra as alterações causadas pela retinopatia diabética induzida por estreptozotocina

ABSTRACT Purpose: This study investigates the protective effect of cilostazol on the development and evolution of diabetic retinopathy in rats. Methods: Sixty male rats were divided into four groups: untreated nondiabetic rats, untreated diabetic rats, cilostazol-treated nondiabetic rats, and cilostazol-treated diabetic rats. The thickness of the internal limiting membrane to the outer limiting membrane, inner plexiform layer, inner nuclear layer, and outer nuclear layer were measured. The number of cell nuclei per 50-μm length in retinal sections was counted to quantify the degree of retinal cell loss. Results: The number of nuclei in the ganglion cell layer was significantly higher in untreated nondiabetic rats (p<0.05). The mean number of nuclei in the cilostazol-treated nondiabetic rats was significantly higher than that in the cilostazol-treated diabetic rats (p<0.05). The cilostazol-treated nondiabetic rats had a significantly higher mean nuclei count in the inner nuclear layer and inner plexiform layer as compared with the other groups (p<0.05). The total mean retinal thickness of the cilostazol-treated nondiabetic rats was significantly higher than that of cilostazol-treated diabetic rats and untreated diabetic rats (p<0.05). Conclusion: By decreasing the loss of ganglion cells and reducing the sensorineural atrophy in the internal retinal layers, cilostazol had a protective effect against changes caused by diabetic retinopathy in diabetic rats.

RESUMO Objetivo: O objetivo deste estudo foi investigar o efeito protetor do cilostazol no desenvolvimento e na evolução da retinopatia diabética em ratos. Métodos: Sessenta ratos machos foram divididos em 4 grupos: ratos não-diabéticos não-tratados, ratos diabéticos não-tratados, ratos não-diabéticos tratados com cilostazol e ratos diabéticos tratados com cilostazol. A espessura da membrana limitante interna à membrana limitante externa, a camada plexiforme interna, a camada nuclear interna e a camada nuclear externa foram medidas. Para quantificar o grau de perda de células da retina, foi contado o número de núcleos de células por 50 μm de comprimento em secções retinianas. Resultados: O número de núcleos no GCL foi significativamente maior em Ratos não-diabéticos não-tratados com cilostazol (p<0,05). O número médio de núcleos em Ratos não-diabéticos tratados com cilostazol foi significativamente maior do que em Ratos diabéticos tratados com cilostazol (p<0,05). A contagem média de núcleos em camada nuclear interna e camada plexiforme interna de ratos não-diabéticos tratados com cilostazol foi significativamente maior do que nos outros grupos (p<0,05). A espessura retiniana média total de Ratos não-diabéticos tratados com cilostazol foi significativamente maior do que em Ratos diabéticos tratados com cilostazol e Ratos diabéticos não-tratados (p<0,05). Conclusão: Os resultados demonstraram que o cilostazol teve um efeito protetor contra as alterações causadas pela retinopatia diabética em ratos diabéticos, diminuindo a perda de células ganglionares e reduzindo a atrofia neurossensorial nas camadas retinianas internas.

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.

Implant Osseointegration in Grafted Autogenous Bone Blocks Fixed with Screws and Cyanoacrylate-Based Adhesive: Histomorphometric and Micro-CT Analyses.

PURPOSE: To evaluate implant osseointegration in grafted autogenous bone blocks fixed with cyanoacrylate-based adhesive and screws. Also, grafted bone fixed either with an adhesive or screw was evaluated. MATERIALS AND METHODS: Two surgical defects in the parietal region of rabbits (n = 12) were performed in each animal. Autogenous bone blocks obtained were fixed anteriorly with a screw or cyanoacrylate-based adhesive. After 30 and 45 days of grafting procedures, implants were placed in bone blocks. Histomorphometric and microcomputed tomography (micro-CT) analyses of the implant area were performed at 30 days after implant surgery in the screw (n = 6) and adhesive (n = 6) groups. Histomorphometric analyses of bone-grafted areas were performed at 60 and 75 days in the screw (n = 6) and adhesive (n = 6) groups. Histomorphometric evaluations were carried out in implant and grafted bone areas. The micro-CT parameters evaluated were bone-to-implant contact, bone area fraction occupancy, bone volume fraction, trabecular thickness, trabecular separation, and trabecular number. RESULTS: No differences were observed in the micro-CT parameters for the screw and adhesive groups in all experimental periods. However, an increased quantity of immature bone volume was observed on the adhesive group in the grafted area after 75 days. The grafted area in the screw group (75 days) presented a decrease in the volume density of the immature bone compared with the screw group (60 days). There were no differences in both groups and experimental periods in soft tissue in the grafted area. CONCLUSION: No differences were observed in the osseointegration of implants placed in grafted autogenous bone blocks fixed with cyanoacrylate-based adhesive and screws. Therefore, osseointegration in autogenous bone fixed with cyanoacrylate-based adhesive is viable.

Coadministration of ibuprofen/caffeine on bleaching-induced tooth sensitivity: A randomized clinical trial

Abstract This clinical trial evaluated the effect of the coadministration of ibuprofen/caffeine on bleaching-induced tooth sensitivity (TS). A triple-blind, parallel-design, randomized clinical trial was conducted on 84 patients who received ibuprofen/caffeine or placebo capsules. The drugs were administered for 48 hours, starting 1 hour before the in-office bleaching. Two bleaching sessions were performed with 35% hydrogen peroxide gel with 1-week interval. TS was recorded up to 48 hours after dental bleaching with a 0-10 visual analogic scale (VAS) and a 5-point numeric rating scale (NRS). The color was evaluated with VITA Classical and VITA Bleachedguide scales (ΔSGU) and VITA Easyshade spectrophotometer (ΔE*ab and ΔE00). The absolute risk of TS in both groups was evaluated using Fischer's exact test. Comparisons of the TS intensity (NRS and VAS data) were performed by using the Mann-Whitney test and a two-way repeated measures ANOVA, respectively. The color alteration between the groups was compared with the Student's t test. The significance level was 5%. There was no statistically significant difference between the groups for the absolute risk of TS (p = 1.00) or for the intensity of TS (p > 0.05). A bleaching of approximately 7 shade guide units was observed on the Vita Classical and Vita Bleachedguide scales, with no statistical difference between the groups. It was concluded that coadministration of ibuprofen and caffeine did not reduce the absolute risk or intensity of TS and did not interfere with the efficacy of dental bleaching.

Resumo Este ensaio clínico avaliou o efeito da coadministração de ibuprofeno/cafeína na sensibilidade dental decorrente de clareamento (SD). Um estudo clínico randomizado, paralelo, triplo-cego, foi realizado em 84 pacientes que receberam cápsulas de ibuprofeno/cafeína ou placebo. Os fármacos foram administrados por 48 horas, começando 1 hora antes do clareamento em consultório. Duas sessões de clareamento foram realizadas com gel de peróxido de hidrogênio 35% com intervalo de 1 semana. A SD foi registrada até 48 horas após o clareamento dental com uma escala visual analógica (VAS) de 0-10 e uma escala de classificação numérica (NRS) de 5 pontos. A cor foi avaliada com as escalas Vita Classical e Vita Bleachedguide (ΔSGU) e com o espectrômetro Vita Easyshade (ΔE*ab e ΔE00). O risco absoluto de SD em ambos os grupos foi avaliado por meio do teste exato de Fischer. As comparações da intensidade da SD (NRS e VAS) foram realizadas utilizando-se o teste Mann-Whitney e uma ANOVA de dois fatores com medidas repetidas, respectivamente. A alteração de cor entre os grupos foi comparada com a o teste t de Student. O nível de significância foi de 5%. Não houve diferença estatisticamente significante entre os grupos para o risco absoluto de SD (p = 1,00) ou para a intensidade de SD (p > 0,05). Observou-se clareamento de aproximadamente 7 unidades nas escalas Vita Classical e Vita Bleachedguide, sem diferença estatística entre os grupos. Concluiu-se que a coadministração de ibuprofeno e cafeína não reduziu o risco absoluto ou intensidade da SD e não interferiu na eficácia do clareamento dental.

Ursolic acid-loaded lipid-core nanocapsules reduce damage caused by estrogen deficiency in wound healing.

The skin aging process in women is accelerated due to decreases in serum estrogen levels triggered by the menopause process. Hence, poly(L-lactic acid) lipid-core nanocapsules containing ursolic acid (NPLA-UA) were developed using the interfacial deposition of the preformed polymer methodology as a strategy to reduce damages to the healing process caused by hormonal deficiency in ovariectomized rats. The colloidal suspensions of nanocapsules presented adequate size and morphology (254 and 375 nm), negative zeta potential (-31 and -37 mV), high encapsulation efficiency (99.89 %), and amorphous character. The analyses performed in an in vivo healing trial showed that the treatment with NPLA-UA resulted in faster wound retraction with less inflammatory response. In addition, the angiogenic process was stimulated increased synthesis of dermal collagen occurred. Ursolic acid-loaded, lipid-core nanocapsules are suitable for treating skin changes triggered by decreased estrogen in menopause.

Influence of radiant exposure values from two third generation LED curing units on polymerization profile and microhardness of orthodontic composite under ceramic and metallic brackets

ABSTRACT Introduction: Third generation of LED light curing units might be used in short exposure periods for orthodontic brackets bonding. Objective: This study evaluated the effect of the different radiant exposure (RE) values: Manufacturers' instructions (MI), ½ MI, 1/4 MI and Turbo mode. Two third-generation LED curing units were used: VALO® and Bluephase 20i® . The degree of conversion (DC) and Vickers hardness (VHN) of an orthodontic composite (OC) (Transbond XT) under metallic (MB) or ceramic brackets (CB) were measured. Methods: OC was applied to the bracket base, which was then placed over an attenuated total reflectance (ATR) table coupled to an infrared light spectroscope, or to a glass surface for the VHN analysis. The specimens were light-cured and DC values were calculated. The VHN was obtained in a microhardness tester. The data were analyzed with 2-way ANOVA followed by Tukey's post-hoc test (pre-set α=0.05). Linear regression analysis evaluated the relationship between RE values and dependent variables. Results: CB allowed higher DC and VHN values than MB (p< 0.001). No significant difference was noted among groups when CB were used. For MB, MI groups showed the highest DC and VHN values. A significant, but weak relationship was found between delivered RE values and dependent variables. Conclusions: The decrease in RE values from third generation LED CU did not jeopardize the DC values when CB were used, but can compromise DC and VHN values when MB are used.

RESUMO Introdução: A terceira geração de LEDs fotopolimerizadores pode ser utilizada em curtos períodos de exposição para a colagem de braquetes ortodônticos. Objetivo: O presente estudo avaliou o efeito dos diferentes valores de irradiância (IR): instruções do fabricante (IF), ½ IF, » IF e modo Turbo. Dois fotopolimerizadores LED de terceira geração (VALO® e Bluephase20i®) foram utilizados. Foram mensurados o grau de conversão (GC) e a dureza Vickers (VHN) de um compósito ortodôntico (CO) (Transbond XT) sob braquetes metálicos (BM) ou cerâmicos (BC). Métodos: O compósito ortodôntico foi aplicado na base do braquete e foi posicionado sobre uma mesa de refletância total atenuada (ATR) acoplada a um espectroscópio de infravermelho ou a uma superfície de vidro para análise de VHN. As amostras foram fotopolimerizadas e os valores de GC foram calculados. O VHN foi obtido em um microdurômetro. Os dados foram analisados com ANOVA de 2 fatores seguida do teste post-hoc de Tukey (predefinido α = 0,05). A análise de regressão linear avaliou a relação entre os valores de IR e as variáveis dependentes. Resultados: BC permitiu valores maiores de GC e VHN do que BM (p<0,001). Nenhuma diferença significativa foi observada entre os grupos quando BC foi utilizado. Para BM, os grupos de IF mostraram os maiores valores de GC e VHN. Uma relação significativa, mas fraca, entre os valores de IR entregue e as variáveis dependentes foi encontrada. Conclusões: A diminuição dos valores de IR dos fotopolimerizadores LED de terceira geração não prejudicou os valores de GC quando BC foram utilizados, mas pode comprometer os valores de GC e VHN quando BM são utilizados.

Eucalyptus cinerea: Microscopic Profile, Chemical Composition of Essential Oil and its Antioxidant, Microbiological and Cytotoxic Activities

Abstract Eucalyptus species possess anti-inflammatory, antifungal, antibacterial, and insecticidal properties. In this study, the chemical composition and biological activities of Eucalyptus cinerea essential oil (EO) and the leaf and stem anatomy were investigated. EO was extracted by Clevenger apparatus and the compounds were identified by GC/MS. The antioxidant activity was evaluated by DPPH, ABTS, and reducing phosphomolybdenum complex. Broth microdilution was used to determine antimicrobial activity. Cytotoxicity was verified against HeLa, HRT-18, and Calu-3 cells by MTT assay. The cytotoxic mechanism was studied by cell DNA content, cell cycle, and DNA fragmentation. The microscopic analyzes of the leaves and the stems were performed by light microscopy, field emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The main constituent of the EO was 1,8-cineole (55.24%). The EO showed low antioxidant and antimicrobial activities. Calu-3 cells showed a significant reduction in viability with IC50 of 689.79 ± 29.34 μg/mL. EO at 1000 μg/mL decreased the DNA content in Jurkat cells. In general, EO increased cell percentage in sub-G0 and S phases with concomitant reduction of cell percentage in G0/G1 and G2/M phases and provided DNA fragmentation of 29.73%. Anatomical and micromorphological features of the leaves and stems can help in the species identification and its differentiation from other Eucalyptus species.

Analysis of diagnostic criteria for ventilator-associated pneumonia: a cohort study / Análisis de criterios diagnósticos de neumonía asociada a la ventilación mecánica: estudio de cohorte / Análise dos critérios diagnósticos de pneumonia associada à ventilação mecânica: estudo de coorte

ABSTRACT Objectives: to analyze the diagnostic criteria for ventilator-associated pneumonia recommended by the Brazilian Health Regulatory Agency and the National Healthcare Safety Network/Centers for Disease Control and Prevention, as well as its risk factors. Methods: retrospective cohort study carried out in an intensive care unit throughout 12 months, in 2017. Analyses included chi-square, simple linear regression, and Kappa statistical tests and were conducted using Stata 12 software. Results: the sample was 543 patients who were in the intensive care unit and under mechanical ventilation, of whom 330 (60.9%) were men and 213 (39.1%) were women. Variables such as gender, age, time under mechanical ventilation, and oral hygiene proved to be significant risk factors for the development of ventilator-associated pneumonia. Conclusions: patients submitted to mechanical ventilation need to be constantly evaluated so the used diagnostic methods can be accurate and applied in an objective and standardized way in Brazilian hospitals.

RESUMEN Objetivos: analizar los criterios diagnósticos de neumonía asociada la ventilación mecánica recomendados por la Agencia Nacional de Vigilancia Sanitaria y la National Health Care Safety Network/CDC, así como los factores de riesgo. Métodos: estudio de cohorte retrospectivo realizado en una unidad de terapia intensiva durante 12 meses, en 2017. El análisis se realizó mediante pruebas estadísticas de Chi-cuadrado, regresión lineal simple y test de Kappa, utilizando el programa STATA 12. Resultados: muestra constituida por 543 pacientes hospitalizados en UTI con ventilación mecánica, de ellos 330 (60,9%) eran de sexo masculino, y 213 (39,1%) de sexo femenino. Las variables como sexo, edad, tiempo de ventilación e higiene oral fueron significativas como factores de riesgo para el desarrollo de la NAV. Conclusiones: los pacientes en uso de ventilación mecánica requieren evaluación constante de precisión en los métodos de diagnóstico de manera objetiva y estandarizada en las instituciones hospitalarias brasileñas.

RESUMO Objetivos: analisar os critérios diagnósticos da Pneumonia Associada à Ventilação Mecânica recomendados pela Agência Nacional de Vigilância Sanitária e pela National Healthcare Safety Network/CDC, bem como os fatores de risco. Métodos: estudo de coorte retrospectivo realizado em uma Unidade de Terapia Intensiva, no período de 12 meses, no ano de 2017. A análise foi realizada por meio de testes estatísticos Qui-Quadrado, regressão linear simples e teste de Kappa, pelo programa STATA 12. Resultados: a amostra constitui-se de 543 pacientes hospitalizados na UTI em ventilação mecânica, destes, 330 (60,9%) eram do sexo masculino e 213 (39,1%) eram do sexo feminino. As variáveis, como sexo, idade, tempo de ventilação e higiene oral, foram significativas como fatores de risco para o desenvolvimento da Pneumonia Associada à Ventilação Mecânica (PAV). Conclusões: os pacientes em uso da ventilação mecânica necessitam de constante avaliação para acurácia dos métodos de diagnósticos, de forma objetiva e padronizada, nas instituições hospitalares brasileiras.

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.

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.

Surface morphology and in vitro leachability of soft liners modified by the incorporation of antifungals for denture stomatitis treatment

Abstract Objective: To evaluate the surface morphology and in vitro leachability of temporary soft linings modified by the incorporation of antifungals in minimum inhibitory concentrations (MIC) for Candida albicans biofilm. Methodology:Specimens of soft lining materials Softone and Trusoft were made without (control) or with the addition of nystatin (Ny), miconazole (Mc), ketoconazole (Ke), chlorhexidine diacetate (Chx), or itraconazole (It) at their MIC for C. albicans biofilm. The surface analyses were performed using Confocal laser scanning microscopy after 24 h, 7 days, or 14 days of immersion in distilled water at 37ºC. In vitro leachability of Chx or Ny from the modified materials was also measured using Ultraviolet visible spectroscopy for up to 14 days of immersion in distilled water at 37ºC. Data (µg/mL) were submitted to ANOVA 1-factor/Bonferroni (α=0.05). Results: Softone had a more irregular surface than Trusoft. Morphological changes were noted in both materials with increasing immersion time, particularly, in those containing drugs. Groups containing Chx and It presented extremely porous and irregular surfaces. Both materials had biexponential release kinetics. Softone leached a higher concentration of the antifungals than Trusoft (p=0.004), and chlorhexidine was released at a higher concentration than nystatin (p<0.001). Conclusions: The surface of the soft lining materials changed more significantly with the addition of Chx or It. Softone released a higher concentration of drugs than Trusoft did, guiding the future treatment of denture stomatitis.

Ocotea porosa: Anatomy and Histochemistry of Leaves and Stems, Chemical Composition, Cytotoxicity and Insecticidal Activities of Essential Oil

Abstract Ocotea porosa (Nees & Mart.) Barroso, commonly known as "imbuia", "canela-imbuia" or "imbuia-amarela" in Brazil, is a tree of the Southern Atlantic Forest. The present study investigates the anatomy of leaf and stem, volatile oil chemistry, as well as cytotoxicity and insecticidal activities of the essential oil of O. porosa. Species identification was achieved by anatomy features, mainly due to paracytic and anomocytic stomata; non-glandular trichomes; biconvex midrib and petiole with a collateral open arc vascular bundle; presence of a sclerenchymatous layer, starch grains and crystal sand in the stem; and the presence of phenolic compounds in the epidermis, phloem and xylem of the midrib, petiole and stem. The main volatile components of the essential oil were α-pinene (19.71%), β-pinene (13.86%) and bicyclogermacrene (24.62%). Cytotoxicity against human cancer cell (MCF-7), mouse cancer cell (B16F10) and mouse non-tumoral cell (McCoy) was observed as well as insecticidal activity of the essential oil against susceptible 'Ft. Dix' bed bugs (Cimex lectularius L.) by topical application.

PEG-PCL Nanocapsules Containing Curcumin: Validation of HPLC Method for Analyzing Drug-loading Efficiency, Stability Testing and Cytotoxicity on NIH-3T3 Cell Line

Abstract Curcumin (CUR) shows potential use for treating cancer. However, CUR has low solubility and reduced bioavailability, which limit its clinical effect. Therefore, the development of nanocarriers can overcome these problems and can ensure the desired pharmacological effect. In addition, it is mandatory to prove the quality, the efficacy, and the safety for a novel nanomedicine to be approved. In that sense, this paper aimed (a) to prepare CUR-loaded polyethylene glycol-poly(ε-caprolactone) nanocapsules; (b) to validate an analytical method by high performance liquid chromatography (HPLC) for quantifying CUR in these nanoformulations; (c) to evaluate the physicochemical stability of these formulations; and to investigate their cytotoxicity on NIH-3T3 mouse fibroblast cells. The HPLC method was specific to CUR in the loaded nanocapsules, linear (r = 0.9994) in a range of 10.0 to 90.0 µg.mL-1 with limits of detection and quantification of 0.160 and 0.480 µg.mL-1, respectively. Precision was demonstrated by a relative standard deviation lower than 5%. Suitable accuracy (102.37 ± 0.92%) was obtained. Values of pH, particle size, polydispersity index, and zeta potential presented no statistical difference (p > 0.05) for CUR-loaded nanoparticles. No cytotoxicity was observed against NIH-3T3 mouse embryo fibroblast cell line using both the tetrazolium salt and sulforhodamine B assays. In conclusion, a simple and inexpensive HPLC method was validated for the CUR quantification in the suspensions of nanocapsules. The obtained polymeric nanocapsules containing CUR showed suitable results for all the performed assays and can be further investigated as a feasible novel approach for cancer treatment.

Effect of Cilostazol-Loaded PCL/PEG Nanocapsules on Abdominal Aortic Tunics and Lipid Profile of Wistar Rats

Abstract Cilostazol (CLZ) is a phosphodiesterase III inhibitor with antiplatelet and vasodilator properties. It has been recently verified that CLZ plays a significant role in the arteries by inhibiting the proliferation and growth of muscle cells, increasing the release of nitric oxide by the endothelium and promoting angiogenesis. Considering these promising effects, the use of nanocapsules may be an interesting strategy to optimize its pharmacokinetics and pharmacodynamics at the vascular level for preventing atherosclerosis. The aim of this study was to evaluate the effect of cilostazol-loaded nanocapsules in the abdominal aortic tunics and on the lipid profile of Wistar rats in order to investigate its potential role in the prevention of atherosclerosis. Thirty-two animals were divided into four groups of eight animals, with 30-day treatment. Group 1 received nanoencapsulated CLZ; Group 2, control nanocapsules with no drug; Group 3, propylene glycol and water; and Group 4, a solution of CLZ in propylene glycol and water. After 30 days, there was no statistically significant difference between the groups regarding the cellularity and thickness of the arterial tunics of the abdominal aorta. However, the group that received nanoencapsulated CLZ (Group 1) had an improvement in HDL-c and triglyceride values compared to unloaded nanocapsules (Group 2).

Preparation and characterization of liposomes loaded with silver nanoparticles obtained by green synthesis

The objective of this work was to develop and characterize liposomes loaded with silver nanoparticles (LAgNPs) to show improvement in stability characteristics. AgNPs were prepared by the green synthesis method with Aloe vera gel extract and exposure to sunlight. Liposomes were prepared by the modified reverse phase method. Particle size, polydispersity index, zeta potential, as well as the scanning electron microscopy (SEM) morphological aspects of AgNPs and LAgNPs were evaluated. In addition, was used flame atomic absorption spectroscopy to determine the amount of AgNP that was encapsulated in liposomes. The AgNPs presented as amorphous and polydisperse structures, with a mean diameter of 278.46 nm and zeta potential of -18.3 mV. LAgNPs had a mean diameter between 321 and 373 nm, the polydispersity index close to 0.2 and a zeta potential around -40 mV, which indicates greater stability to the AgNPs. The images obtained by SEM show semicircular structures for AgNPs and well-defined spherical shape for LAgNPs. The percentage of encapsulation was between 51.81 to 58.83%. These results showed that LAgNPs were obtained with adequate physicochemical characteristics as a release system.

Preparation and characterization of a novel antimicrobial film dressing for wound healing application

Antibacterial activity and good mechanical properties are some of the characteristics required for an appropriate film dressing. A novel polymer blend was developed for wound healing application. Twenty-four formulations using the polymers chitosan, poly(vinyl alcohol) and/or ɛ-Polylysine and the plasticizer glycerol were designed using factorial design and then the films were prepared by the casting/solvent evaporation method. Seventeen films were obtained among the twenty-four proposed formulations that were characterized by Field Emission Scanning Electron Microscopy (FE-SEM) and Fourier Transform Infrared Spectroscopy (FTIR). Mechanical properties, such as tensile strength (σ), elongation at break (ɛ) and Young's modulus (Y) as well as antibacterial properties were determined. The best candidate was then further analyzed with regard to porosity, Water Vapor Transmission Rate (WVTR), swelling and cytotoxicity experiments. The results showed a film with semi-occlusive characteristics, good mechanical properties and no toxic. Incorporation of ɛ-Polylysine increased antibacterial activity against gram-negative (Escherichia coli) and gram-positive (Staphylococcus aureus) bacteria

Liposomal anesthetic gel for pain control during periodontal therapy in adults: a placebo-controlled RCT

Abstract Periodontal therapy usually requires local anesthesia. If effective, a non-invasive, liposomal anesthetic gel could increase the levels of acceptance of patients in relation to periodontal therapy. Objective: This study investigated the efficacy of liposomal anesthetic gel for pain control during periodontal therapy. Methodology: Forty volunteers with moderate to severe chronic periodontitis were recruited, of which at least three sextants required periodontal therapy. At least one of the selected teeth had one site with a probing depth of ≥4 mm. The volunteers received the following three gels: a placebo, lidocaine/prilocaine (Oraqix®), or a liposomal lidocaine/prilocaine, which were applied to different sextants. Pain frequency was registered during treatment and the volunteers received a digital counter to register any painful or uncomfortable experiences. At the end of each session, the volunteers indicated their pain intensity using rating scales (NRS-101 and VRS-4). The volunteers had their hemodynamic parameters measured by a non-invasive digital monitor. Results: Pain frequency/intensity did not show statistical difference between intervention groups. The tested gels did not interfere with the hemodynamic indices. Dental anxiety, suppuration and probing depth could influence pain during periodontal therapy. Conclusion: Our results suggest limited indications for the use of non-invasive anesthesia when used for scaling and root planing. Intra-pocket anesthetic gel could be a good option for anxious patients, or those who have a fear of needles.

Long-lasting anti-platelet activity of cilostazol from poly(ε-caprolactone)-poly(ethylene glycol) blend nanocapsules.

Cilostazol (CLZ) acts as a vasodilator and antiplatelet agent and is the main drug for the treatment of intermittent claudication (IC) related to peripheral arterial disease (PAD). The usual oral dose is 100 mg twice a day, which represents a disadvantage in treatment compliance. CLZ presents several side effects, such as headache, runny nose, and dizziness. This paper aimed to obtain novel polymeric nanocapsules prepared from poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) blend containing CLZ. Nanocapsules showed pH values between 6.1 and 6.3, average size lower than 137 nm, low polydispersity index (<0.22) and negative zeta potential. These nanoformulations demonstrated spherical shape with smooth surface. Results achieved by X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated drug amorphization compared to pure CLZ. Fourier-transformed infrared spectroscopy (FTIR) showed no chemical bonds between drug and polymers. Formulations presented suitable stability for physical parameters. The in vitro drug release demonstrated prolonged release with no burst effect. Drug release was controlled by both mechanisms of polymer relaxation/degradation and Fickian diffusion. Moreover, chosen CLZ-loaded nanocapsules provided an in vivo prolonged antiplatelet effect for CLZ statistically similar to aspirin. These formulations can be further used as a feasible oral drug delivery carrier for controlled release of CLZ in order to treat PAD and IC events.

Characterization and Cytotoxic Evaluation of Silver and Gold Nanoparticles Produced with Aqueous Extract of Lavandula dentata L. in Relation to K-562 Cell Line

Abstract Metallic nanoparticles have great potential as a chemotherapeutic agent. The aim of this study was to develop and characterize silver and gold nanoparticles using a simple method, as well as evaluating the potential cytotoxic activity in relation to the K-562 cell line. For the synthesis, a solution containing the metallic ions was subjected to magnetic stirring with the aqueous extract of Lavandula dentata L. and a change of colour was observed. With the data obtained from the analyses we concluded that the nanoparticles were successfully obtained by a simple and green method using the aqueous extract of L. dentata. The obtained nanoparticles presented a reduced size, a low level of polydispersion, and a homogenous spherical shape. The nanoparticles presented intense and characteristic diffraction peaks, which could be correlated to the planes of the centred cubic structure of the silver and gold. The two formulations presented predominantly crystalline characteristics. The infrared analysis suggested that the amides and alcohols present in the samples may have been responsible for the reduction and limitation of the size and dispersion of the silver and gold nanoparticles. The cytotoxic assay showed that the nanoparticles demonstrated great potential to reduce the cell viability of the K-562 cell line, especially the gold nanoparticles.