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INTRODUCTION: This review aimed at investigating the impact of bundle components on the prevention of ventilator-associated pneumonia (VAP) in adults and the elderly. METHODOLOGY: The databases consulted were PubMed, EBSCO, and Scielo. The terms Bundle and Pneumonia were searched in combination. The original articles were selected in Spanish and English; published between January 2008 and December 2017. After eliminating the duplicate papers, an analysis of the titles and the abstracts was performed in order to select the assessed articles. A total of 18 articles were included in this review that were evaluated according to the following criteria: research reference, country of data collection, type of study, characteristics of the studied patients, analysis and intervention performed, bundle items investigated and their results, and research outcome. RESULTS: Four bundle items were presented in all the investigated papers. 61% of those works were considered from seven to eight bundle items. Daily evaluation of sedation interruption and daily assessment for verifying extubation condition, head-of-bed elevation at 30 degrees, cuff pressure monitoring, coagulation prophylaxis, and oral hygiene were the most reported bundle items. One study described the increased mortality of patients under mechanical ventilation when omitted the bundle items of oral hygiene and stress ulcer prophylaxis. Head-of-bed elevation at 30 degrees was the item reported in 100% of the studied papers. CONCLUSIONS: Existing research demonstrated that VAP reduction occurred when bundle items were performed for adults and the elderly. Four works showed the relevance of team education as a central approach to the event reduction related to the ventilator.
Assuntos
Úlcera Péptica , Pneumonia Associada à Ventilação Mecânica , Adulto , Humanos , Idoso , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Unidades de Terapia Intensiva , Respiração Artificial , Ventiladores MecânicosRESUMO
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.
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BACKGROUND: Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug. METHODS: Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed. RESULTS: TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticulate systems presented a spherical shape with a smooth and regular surface, adequate diameter (226 to 250 nm), polydispersity index below 0.3, and suitable electrical stability (-38 to -42 mV). X-ray diffraction confirmed that the encapsulation method provided mainly the drug molecular dispersion in the nanocapsule oily core. Fourier-transform infrared spectra suggested that nanoencapsulation did not result in chemical bonds between drug and polymer. In vitro drug dissolution experiments showed a controlled release with a slight initial burst. The release kinetics showed zero-order kinetics. As per the Korsmeyer-Peppas model, anomalous transport features were observed. TAC-loaded PCL nanocapsules exhibited excellent anti-inflammatory activity when compared to the free drug. CONCLUSIONS: TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.
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In this study, the preparation and characterization of three hydroxyapatite-based bioactive scaffolds, including hydroxyapatite microspheres (HAps), amoxicillin-hydroxyapatite composite (Amx-HAp), and collagen-hydroxyapatite composite (Col-HAp) were performed. In addition, their behavior in human dental pulp mesenchymal stem cell (hDPSC) culture was investigated. HAps were synthesized through the following methods: microwave hydrothermal, hydrothermal reactor, and precipitation, respectively. hDPSCs were obtained from samples of third molars and characterized by immunophenotypic analysis. Cells were cultured on scaffolds with osteogenic differentiation medium and maintained for 21 days. Cytotoxicity analysis and migration assay of hDPSCs were evaluated. After 21 days of induction, no differences in genes expression were observed. hDPSCs highly expressed the collagen IA and the osteonectin at the mRNA. The cytotoxicity assay using hDPSCs demonstrated that the Col-HAp group presented non-viable cells statistically lower than the control group (p = 0.03). In the migration assay, after 24 h HAps revealed the same migration behavior for hDPSCs observed compared to the positive control. Col-HAp also provided a statistically significant higher migration of hDPSCs than HAps (p = 0.02). Migration results after 48 h for HAps was intermediate from those achieved by the control groups. There was no statistical difference between the positive control and Col-HAp. Specifically, this study demonstrated that hydroxyapatite-based bioactive scaffolds, especially Col-Hap, enhanced the dynamic parameters of cell viability and cell migration capacities for hDPSCs, resulting in suitable adhesion, proliferation, and differentiation of this osteogenic lineage. These data presented are of high clinical importance and hold promise for application in therapeutic areas, because Col-HAp can be used in ridge preservation, minor bone augmentation, and periodontal regeneration. The development of novel hydroxyapatite-based bioactive scaffolds with clinical safety for bone formation from hDPSCs is an important yet challenging task both in biomaterials and cell biology.
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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.
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Pneumonia Associada à Ventilação Mecânica , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Respiração Artificial/efeitos adversos , Estudos RetrospectivosRESUMO
The aim of this paper was to use chromatographic tools for validating an analytical method for the tacrolimus (TAC) determination in polymeric nanocapsules and for identifying the drug degradation products after alkaline stress. A rapid Ultra-High-Performance Liquid Chromatography coupled with photo-diode array (UHPLC-PDA) method was successfully performed using the following chromatographic conditions: the Shimadzu Shim-pack XR-ODS III C18 column (100 mm×2.00 mm, 2.2 µm), the mobile phase consisting of methanol and acidified ultrapure water (89:11 v/v), the flow rate of 0.55 mL·min-1, and the ultraviolet (UV) detection at 235 nm. This method was validated as per International Council for Harmonisation (ICH) guidelines. In addition, a TAC forced degradation assay was carried out after alkaline stress and its degradation products were investigated using Liquid Chromatography coupled tandem mass spectroscopy (LC-MS/MS). The calibration curve was linear in the range of 100.0-300.0 µg·mL-1 (r >0.9999). Accuracy was confirmed by the TAC recovery of 96.55 to 98.19%. Precision (intraday and interday) were demonstrated by relative standard deviation lower than 0.89% and 3.25%, respectively. Selectivity and robustness were also proved. The method developed it was successfully applied to quantify TAC from polymeric nanocapsules, showing a high loading efficiency rate (>96.47%). The main drug degradation product observed in a multiple reaction monitoring (MRM) experiment was m/z 844, confirming the susceptibility of TAC under alkaline conditions; this finding was first time described.
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Nanocápsulas , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Poliésteres , Reprodutibilidade dos Testes , Tacrolimo , Espectrometria de Massas em TandemRESUMO
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.
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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(Æ-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.
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Antineoplásicos/administração & dosagem , Derivados de Benzeno/administração & dosagem , Materiais Biocompatíveis , Glioma/tratamento farmacológico , Nanocápsulas/química , Compostos Organosselênicos/administração & dosagem , Polietilenoglicóis/química , Animais , Antineoplásicos/química , Astrócitos/efeitos dos fármacos , Derivados de Benzeno/química , Compostos Organosselênicos/química , SolubilidadeRESUMO
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.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Celulose/análogos & derivados , Portadores de Fármacos/química , Indóis/administração & dosagem , Dor/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Cápsulas , Celulose/química , Indóis/uso terapêutico , Masculino , CamundongosRESUMO
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.
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Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Portadores de Fármacos , Metotrexato/administração & dosagem , Nanocápsulas , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Fenômenos Químicos , Combinação de Medicamentos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Polietilenoglicóis/química , Análise EspectralRESUMO
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.
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Animais , Camundongos , Curcumina/farmacologia , Células-Tronco Embrionárias/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Testes de Toxicidade , Nanotecnologia , Células NIH 3T3 , Embrião de Mamíferos/citologia , NanocápsulasRESUMO
This study aimed to characterize the physicochemical properties of 3,3'-diindolylmethane (DIM)-loaded nanocapsules (NCs) as well as the antinociceptive effect using distinct animal models (hot plate test, formalin-induced nociception and complete Freud's adjuvant induced paw inflammation). The DIM-loaded NCs (composed by primula oil and ethylcellulose) were characterized using differential scanning calorimetry, thermogravimetric analysis, Fourier-transformed infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. The physicochemical characterization demonstrated that DIM could be molecularly dispersed into the NCs, whose size was nanometric with a spherical shape. An improvement in DIM thermal stability was achieved by its encapsulation and there were no interactions among the formula components. For the nociceptive evaluation, male adult Swiss mice were pretreated with the NCs or free DIM by the intragastric route at the dose of 10â¯mg/Kg (time-response curve), 5 or 2.5â¯mg/Kg (dose-response curve). The behavioral tests were performed over an experimental period of 0.5-8â¯h. Both free and nanoencapsulated DIM reduced the mechanical hypernociception induced by CFA, mitigated nociceptive behavior of formalin-induced neurogenic and inflammatory pain and increased paw withdrawal latency assessed by the hot-plate test. Importantly, the DIM nanoencapsulation promoted a rapid initiation and prolonged the bioactive antinociceptive action (up to 8â¯h) as well as reduced the effective dose in comparison to its free form. In summary, this study reported that the NCs had adequate nanometric size, increased DIM stability and its antinociceptive action in different animal models, suggesting that the formulation may be a possible therapeutic alternative to the management of pain and inflammatory-related pathologies.
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Analgésicos/farmacologia , Edema/tratamento farmacológico , Indóis/farmacologia , Inflamação/tratamento farmacológico , Nanocápsulas/química , Analgésicos/química , Animais , Físico-Química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Formaldeído , Adjuvante de Freund , Indóis/química , Inflamação/induzido quimicamente , Masculino , Camundongos , Medição da Dor , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Adapalene (ADAP) is an important drug widely used in the topical treatment of acne. It is a third-generation retinoid and provides keratolytic, anti-inflammatory, and antiseborrhoic action. However, some topical adverse effects such as erythema, dryness, and scaling have been reported with its commercial formula. In this sense, the microencapsulation of this drug using polyesters can circumvent its topical side effects and can lead to the enhancement of drug delivery into sebaceous glands. The goal of this work was to obtain ADAP-loaded poly(ε-caprolactone) (PCL) microparticles prepared by a simple emulsion/solvent evaporation method. Formulations containing 10 and 20% of ADAP were successfully obtained and characterized by morphological, spectroscopic, and thermal studies. Microparticles presented encapsulation efficiency of ADAP above 98% and showed a smooth surface and spherical shape. Fourier transform infrared spectroscopy (FTIR) results presented no drug-polymer chemical bond, and a differential scanning calorimetry (DSC) technique showed a partial amorphization of the drug. ADAP permeation in the Strat-M membrane for transdermal diffusion testing was evaluated by photoacoustic spectroscopy (PAS) in the spectral region between 225 and 400 nm after 15 min and 3 h from the application of ADAP-loaded PCL formulations. PAS was successfully used for investigating the penetration of polymeric microparticles. In addition, microencapsulation decreased the in vitro transmembrane diffusion of ADAP.
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Adapaleno/administração & dosagem , Portadores de Fármacos , Microesferas , Poliésteres/química , Adapaleno/química , Varredura Diferencial de Calorimetria , Difusão , Sistemas de Liberação de Medicamentos , Emulsões , Membranas Artificiais , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Técnicas Fotoacústicas , Solventes/química , Espectrofotometria , Espectroscopia de Infravermelho com Transformada de Fourier , ÁguaRESUMO
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 100â¯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 137â¯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.
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Cilostazol/farmacologia , Nanocápsulas/química , Inibidores da Agregação Plaquetária/farmacologia , Poliésteres/química , Polietilenoglicóis/química , Animais , Varredura Diferencial de Calorimetria , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Masculino , Nanocápsulas/ultraestrutura , Tamanho da Partícula , Agregação Plaquetária/efeitos dos fármacos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XAssuntos
Antineoplásicos/química , Derivados de Benzeno/química , Nanocápsulas/química , Compostos Organosselênicos/química , Poliésteres/química , Antineoplásicos/farmacologia , Varredura Diferencial de Calorimetria , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Nanocápsulas/toxicidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
This study aimed the development of nanocapsules (NCs) for oral indole-3-carbinol (I3C) administration and evaluation of antinociceptive potential of this compound in its two forms, free and nanoencapsulated, using acute pain models. NCs showed adequate physicochemical characteristics and protected the I3C against UVC radiation exposure. It was observed no chemical bond between I3C and polymer by FTIR. Besides, X-ray and DSC analysis suggested that I3C was molecularly dispersed in NCs. The dialysis bag technique showed that almost 100% of the compound was released from NCs at 360min. Mathematical modeling demonstrated that this release occurred in two rates, with an initial burst effect followed by a slower release of I3C. Regarding the in vivo analysis, time-response curve showed that both forms of I3C caused an inhibition in inflammatory phase of nociception induced by formalin and increased the latency response in hot plate test. Interestingly, NCs were able to prolong the I3C effect in both tests. Furthermore, in dose-response curve, only I3C in its nanoencapsulated form presented effect on inflammatory phase of the formalin test. In conclusion, NCs to I3C incorporation presented adequate nanometric characteristics and prolonged its antinociceptive action in acute pain models tested.
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Analgésicos/administração & dosagem , Portadores de Fármacos/química , Indóis/administração & dosagem , Nanocápsulas/química , Dor/tratamento farmacológico , Raios Ultravioleta , Analgésicos/efeitos da radiação , Analgésicos/uso terapêutico , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Indóis/efeitos da radiação , Indóis/uso terapêutico , Inflamação , Masculino , Camundongos , Dor/imunologia , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
ABSTRACT Ferulic acid (FA) is a phenolic compound with well-known antioxidant potential that can be used as a promising anti-inflammatory and anti-cancer molecule. Furthermore, it has been reported to have neuroprotective activity. One of the main problems, which limit its clinical use, is its low bioavailability when administered orally. This limitation can be circumvented by changes in their structure and/or for preparing lipid-based formulations. The aim of this study was to synthesize a derivative of FA, the hexadecyl ferulate (HF). This compound would be more susceptible to pass through blood-brain barrier (BBB) due to its lipophilic character. The HF was obtained by Steglich esterification and yielded 76.77 ± 1.35%. Its structural characterization was performed by spectroscopic methods of Fourier-transformed infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). FTIR spectrum of HF presented two typical bands of ester group, a C=O ester stretching band at 1725 cm-1 and a C-O stretching band at 1159 cm-1. The 1H and 13C spectral data confirmed the chemical structure of HF. Regarding the 13C NMR spectrum, HF showed a chemical shift at δ 167.39 ppm which corresponded to the carbonyl carbon of the ester group. Concerning the in vitro antioxidant potential, HF had equivalent or improved scavenger activity than FA leading to IC50 values of 0.083 ± 0.009 nmol.mL-1 and 0.027 ± 0.002 nmol.mL-1 in DPPH radical scavenging and ABTS radical cation decolorization assays, respectively. Further studies are required in order to investigate the antioxidant effect of HF in biological media.
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ABSTRACT Skin aging causes changes such as wrinkles and flaccidity leading to a large demand for aesthetic procedures, including dermal filling. A key agent in dermal filling is hyaluronic acid (HA), which is a naturally occurring glycosaminoglycan. However, it is a hydrophilic macromolecule that experiences great difficulty in crossing the skin barrier causing most commercial formulations containing it to be injectable, which in turn brings risks since they involve an invasive technique. In that sense, the aim of this study was to develop and characterize nanoparticles obtained from ionic interaction between HA and lysine (Lys) for use as a potential agent of dermal filling for topical application, increasing and improving its applicability and safety. To this end, nanoparticles were obtained by dripping of Lys over HA under magnetic stirring. A nanometric size was confirmed and a suitable surface charge was obtained by zeta potential. Nanoparticles were almost spherical in shape with a smooth surface. Interaction between raw materials for preparing nanoparticles was studied by FTIR and NMR spectroscopy and an ionic interaction was confirmed. These physicochemical features suggest that obtained nanoparticles can be further used as a topical dermal filling.
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Envelhecimento da Pele/genética , Nanotecnologia/classificação , Ácido Hialurônico/análise , Lisina/análise , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Preenchedores Dérmicos/efeitos adversosRESUMO
This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3µm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects.
Assuntos
Acrilatos , Citoproteção/efeitos dos fármacos , Portadores de Fármacos , Inibidores da Agregação Plaquetária , Polímeros , Acrilatos/química , Acrilatos/farmacocinética , Acrilatos/farmacologia , Linhagem Celular , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacocinética , Ácidos Cumáricos/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Polímeros/química , Polímeros/farmacocinética , Polímeros/farmacologiaRESUMO
A simple stability-indicating HPLC-DAD method was validated for the determination of ferulic acid (FA) in polymeric microparticles. Chromatographic conditions consisted of a RP C18 column (250 mm × 4.60 mm, 5 µm, 110 Å) using a mixture of methanol and water pH 3.0 (48 : 52 v/v) as mobile phase at a flow rate of 1.0 mL/min with UV detection at 320 nm. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of quantification, limit of detection, accuracy, precision, and robustness provided suitable results regarding all parameters investigated. The calibration curve was linear in the concentration range of 10.0-70.0 µg/mL with a correlation coefficient >0.999. Precision (intraday and interday) was demonstrated by a relative standard deviation lower than 2.0%. Accuracy was assessed by the recovery test of FA from polymeric microparticles (99.02% to 100.73%). Specificity showed no interference from the components of polymeric microparticles or from the degradation products derived from acidic, basic, and photolytic conditions. In conclusion, the method is suitable to be applied to assay FA as bulk drug and into polymeric microparticles and can be used for studying its stability and degradation kinetics.