RESUMEN
Wound healing is known to be a complicated and intricate process and commonly classified as chronic or acute. Patients with chronic wounds are of public health concern, and require more attention onto skin lesions, including atopic dermatitis. Despite being a natural process, healing can be impaired by existing chronic de diseases such as diabetes, for example. Recently, wound dressings based in nanotechnology systems have emerged as a viable option to improve the healing process. Current advances in nanotechnology-based systems to release growth factors and bioactive agents represent a great opportunity to develop new therapies for wound treatments. It is essential that healthcare professionals understand the key processes involved in the healing cascade, to maximize care with these patients and minimize the undesirable outcomes of non-healing wounds. Therefore, this review aims to summarize the healing process phases and provide a general overview of dressings based in nanotechnology using biomaterials for the release of active agents in wound site.
RESUMEN
Curcumin (CUR) is a phenolic compound present in some herbs, including Curcuma longa Linn. (turmeric rhizome), with a high bioactive capacity and characteristic yellow color. It is mainly used as a spice, although it has been found that CUR has interesting pharmaceutical properties, acting as a natural antioxidant, anti-inflammatory, antimicrobial, and antitumoral agent. Nonetheless, CUR is a hydrophobic compound with low water solubility, poor chemical stability, and fast metabolism, limiting its use as a pharmacological compound. Smart drug delivery systems (DDS) have been used to overcome its low bioavailability and improve its stability. The current work overviews the literature from the past 10 years on the encapsulation of CUR in nanostructured systems, such as micelles, liposomes, niosomes, nanoemulsions, hydrogels, and nanocomplexes, emphasizing its use and ability in cancer therapy. The studies highlighted in this review have shown that these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged CUR release, and reduced side effects, among other interesting advantages.
Asunto(s)
Curcumina , Nanoestructuras , Neoplasias , Disponibilidad Biológica , Humanos , Micelas , Neoplasias/tratamiento farmacológicoRESUMEN
We generated stable amphiphilic copolymer-based polymeric micelles (PMs) with temperature-responsive properties utilizing Pluronic® L35 and a variety of ionic liquids (ILs) to generate different aqueous two-phase micellar systems (ATPMSs). The partitioning of the hydrophobic model compound curcumin (CCM) into the PM-rich phase and the drug delivery capabilities of the PMs were investigated. ATPMSs formed using more hydrophobic ILs (i.e., [Ch][Hex] ≈ [Ch][But] > [Ch][Pro] > [Ch][Ac] ≈ [Ch]Cl) were the most effective in partitioning (KCCM) and recovering (RECRich) CCM into the PM-rich phase (15.2 < KCCM < 22.0 and 90% < RECRich < 95%, respectively). Moreover, using 1.2 M [Ch][But] and 0.2 M [Ch][Hex] ILs yielded higher encapsulation efficiency (EE) (94.1 and 96.0%, respectively) and drug loading (DL) capacity (14.8 and 16.2%, respectively), together with an increase in the average hydrodynamic diameter of the PMs (DH) (42.5 and 45.6 nm, respectively). The CCM-PM formulations were stable at 4.0, 25.0, and 37.0 °C and the release of CCM was faster with the less hydrophobic ILs (i.e., [Ch]Cl and [Ch][Ac]). Furthermore, due to the lower critical solution temperature properties of Pluronic® L35, the PMs exhibit temperature responsiveness at 37.0 °C. In vitro cytotoxicity assays were also performed to determine the potency of CCM-PM formulations, and a 1.8-fold decrease in IC50 values was observed between the CCM-PMs/[Ch][Hex] and CCM-PMs/[Ch]Cl formulations for PC3 cells. The lower IC50 value for the [Ch][Hex] version corresponded to a greater potency compared to the [Ch]Cl version, since a lower concentration of CCM was required to achieve the same therapeutic effect. The ATPMSs investigated in this study serve as a novel platform for Pluronic® L35/PBS buffer (pH 7.4) + IL-based ATPMS development. The unique properties reported here may be useful in applications such as controlled-release drug delivery systems (DDS), encapsulation, and bioseparations.
Asunto(s)
Líquidos Iónicos , Micelas , Portadores de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , PolímerosRESUMEN
The protective antioxidant activity of acetylcysteine (NAC) against toxicity due to cisplatin has been reported in experimental models; however, its efficacy in patients has not been elucidated. The aim of this study was to investigate the possible protective effect of NAC on cisplatin-induced toxicity and the effect of NAC on clinical response and oxidative stress in patients treated for head and neck cancer. This was a randomized, double-blind, placebo-controlled trial conducted in patients receiving high-dose cisplatin chemotherapy concomitant to radiotherapy. Patients were randomly assigned to groups and received: (a) 600 mg NAC syrup, orally once daily at night for 7 consecutive days or (b) placebo, administered similarly to NAC. Nephro-, oto-, hepato-, myelo-, and gastrointestinal toxicities, clinical responses, and plasma and cellular markers of oxidative stress were evaluated. Fifty-seven patients were included (n = 28, NAC arm; and n = 29, placebo arm). A high prevalence of most types of toxicities was observed after cisplatin chemotherapy; however, the parameters were similar between the two groups. There was a predominance of partial response to treatment. In the cellular and plasmatic oxidative stress analyses, minor differences were observed. Overall, there was no statistically significant difference between the groups for all outcomes. These findings show that low-dose oral NAC does not protect patients with head and neck cancer from cisplatin-induced toxicities and oxidative stress. The antitumor efficacy of cisplatin was apparently not impaired by NAC.
Asunto(s)
Acetilcisteína/administración & dosificación , Cisplatino/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Neoplasias de Cabeza y Cuello/terapia , Estrés Oxidativo/efectos de los fármacos , Acetilcisteína/farmacología , Administración Oral , Anciano , Quimioradioterapia/efectos adversos , Cisplatino/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of this study was to report number, type and severity of prescribing errors and pharmacist interventions in high-risk pregnant and postpartum women. DESIGN: A prospective cross-sectional, observational study. SETTING: A high-risk obstetric inpatient unit of a Women's Hospital in Brazil. PARTICIPANTS: About 1826 electronic prescriptions for 549 women in the high-risk obstetrics inpatient unit were included. INTERVENTIONS: When the pharmacist detected potential prescribing errors, interventions were suggested. MAIN OUTCOME MEASURES: Prescriptions were evaluated by clinical pharmacist to identify the type, frequency and severity of prescribing errors and rate of clinical pharmacist intervention acceptance in a high-risk obstetric inpatient. RESULTS: A total of 1826 prescriptions were reviewed with 128 errors (7.0%). The most frequent errors were drug interaction (43.8%), incorrect frequency (21.5%) and improper dose (13.1%). One-hundred and sixty-eight interventions were made by pharmacists, 98.8% of which were accepted by prescribers. Higher maternal age (OR 1.0 (95%CI 1.0-1.1)), higher number of prescribed medications (OR 1.2 (95%CI 1.1-1.3)), obstetric conditions (OR 2.2 (95%CI 1.4-3.3)) and non-breastfeeding postpartum women (OR 3.9 (95% CI 2.5-6.1)) were the independent factors associated with prescribing errors identified through multivariate analysis. CONCLUSIONS: The most common prescription errors related to drug interactions, incorrect frequency and higher number of prescribed medications. The rate of pharmacist acceptance intervention was high.
Asunto(s)
Errores de Medicación/prevención & control , Servicio de Farmacia en Hospital/métodos , Periodo Posparto/efectos de los fármacos , Embarazo de Alto Riesgo/efectos de los fármacos , Factores de Edad , Brasil , Estudios Transversales , Femenino , Hospitales de Enseñanza , Humanos , Pacientes Internos , Farmacéuticos , Embarazo , Estudios ProspectivosAsunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Células Escamosas/terapia , Cisplatino/efectos adversos , Neoplasias de Cabeza y Cuello/terapia , Peróxidos Lipídicos/orina , Malondialdehído/orina , Nitritos/orina , Estrés Oxidativo/efectos de los fármacos , Radioterapia/métodos , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Biomarcadores/orina , Carcinoma de Células Escamosas/orina , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Neoplasias de Cabeza y Cuello/orina , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/efectos de la radiación , Estudios ProspectivosRESUMEN
This works reports the purification of bromelain extracted from Ananas comosus industrial residues by ethanol purification, its partial characterization from the crude extract as well as the ethanol purified enzyme, and its application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels. Bromelain was recovered within the 30-70 % ethanol fraction, which achieved a purification factor of 3.12-fold, and yielded more than 90 % of its initial activity. The resulting purified bromelain contained more than 360 U · mg(-1), with a maximum working temperature of 60â°C and pH of 8.0. Poly(N-isopropylacrylamide)-co-acrylamide hydrogels presented a swelling rate of 125 %, which was capable of loading 56 % of bromelain from the solution, and was able to release up to 91 % of the retained bromelain. Ethanol precipitation is suitable for bromelain recovery and application onto poly(N-isopropylacrylamide)-co-acrylamide hydrogels based on its processing time and the applied ethanol prices.
Asunto(s)
Acrilamida , Resinas Acrílicas , Ananas/química , Bromelaínas/administración & dosificación , Preparaciones de Acción Retardada , Hidrogeles , Bromelaínas/química , Bromelaínas/aislamiento & purificación , Hidrogeles/químicaRESUMEN
BACKGROUND: Caryocar brasiliense Camb (Pequi) is a typical Brazilian Cerrado fruit tree. Its fruit is used as a vitamin source for culinary purposes and as a source of oil for the manufacture of cosmetics. C. brasiliense supercritical CO2 extracts exhibit antimicrobial activity against the bacteria Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and also possess antioxidant activity. This study was designed to evaluate the in vitro cytotoxicity and phototoxicity of the supercritical CO2 extract obtained from the leaves of this species. METHODS: In vitro cytotoxicity and phototoxicity of C. brasiliense supercritical CO2 extracts were assessed using a tetrazolium-based colorimetric assay (XTT) and Neutral Red methods. RESULTS: We found that the C. brasiliense (Pequi) extract obtained by supercritical CO2 extraction did not present cytotoxic and phototoxic hazards. CONCLUSIONS: This finding suggests that the extract may be useful for the development of cosmetic and/or pharmaceutical products.
Asunto(s)
Antibacterianos/efectos adversos , Ericales/efectos adversos , Fibroblastos/efectos de los fármacos , Extractos Vegetales/efectos adversos , Hojas de la Planta , Células 3T3 , Animales , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Brasil , Frutas , Ratones , Extractos Vegetales/farmacologíaRESUMEN
BACKGROUND: The cosmetic and pharmaceutical industries have an increasing interest in replacing synthetic antimicrobials in dermatological products due to increased microbial resistance to conventional antimicrobial agents. Pequi (Caryocar brasiliense) is a native fruit tree of the Brazilian Cerrado, specifically used in cosmetics, in the food industry, and for medicinal purposes. Leishmanicidal and antifungal activities have been reported previously. This study was designed to evaluate the antimicrobial and antioxidant activities of a C. brasiliense extract obtained by supercritical CO2 extraction. METHODS: The minimum inhibitory concentrations (MICs) against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were determined by the classical microdilution method. Antiseptic activity against these organisms was evaluated by the plate diffusion method. The antioxidant potential of the extract was evaluated using a method based on the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The extract's chemical profile was analyzed for the presence of alkaloids, saponins, anthraquinones, steroids, tannins, flavonoids, and phenolic compounds according to standard colorimetric methods. RESULTS: The C. brasiliense supercritical CO2 extract exhibits antimicrobial activity against all bacteria tested. It also possesses antioxidant activity, when compared to a vitamin E standard. CONCLUSIONS: The C. brasiliense supercritical CO2 extract may be useful for the development of personal care products, primarily for antiseptic skin products that inactivate, reduce, prevent, or arrest the growth of microorganisms with the inherent intent to mitigate or prevent disease as well as products that minimize damage caused by free radicals.
Asunto(s)
Antibacterianos/farmacología , Antioxidantes/farmacología , Ericales/química , Escherichia coli/efectos de los fármacos , Extractos Vegetales/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/análisis , Antioxidantes/análisis , Benzotiazoles/metabolismo , Brasil , Cosméticos , Humanos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Ácidos Sulfónicos/metabolismoRESUMEN
Protein structure and function can be regulated by no specific interactions, such as ionic interactions in the presence of salts. Green fluorescent protein (GFP) shows remarkable structural stability and high fluorescence; its stability can be directly related to its fluorescence output, among other characteristics. GFP is stable under increasing temperatures, and its thermal denaturation is highly reproducible. The aim of this study was to evaluate the thermal stability of GFP in the presence of different salts at several concentrations and exposed to constant temperatures, in a range of 70-95°C. Thermal stability was expressed in decimal reduction time. It was observed that the D-values obtained were higher in the presence of citrate and phosphate, when compared with that obtained in their absence, indicating that these salts stabilized the protein against thermal denaturation.
Asunto(s)
Citratos/química , Proteínas Fluorescentes Verdes/química , Fosfatos/química , Calor , Desnaturalización ProteicaRESUMEN
In biotechnology, endotoxin (LPS) removal from recombinant proteins is a critical and challenging step in the preparation of injectable therapeutics, as endotoxin is a natural component of bacterial expression systems widely used to manufacture therapeutic proteins. The viability of large-scale industrial production of recombinant biomolecules of pharmaceutical interest significantly depends on the separation and purification techniques used. The aim of this work was to evaluate the use of aqueous two-phase micellar system (ATPMS) for endotoxin removal from preparations containing recombinant proteins of pharmaceutical interest, such as green fluorescent protein (GFPuv). Partition assays were carried out initially using pure LPS, and afterwards in the presence of E. coli cell lysate. The ATPMS technology proved to be effective in GFPuv recovery, preferentially into the micelle-poor phase (K(GFPuv) < 1.00), and LPS removal into the micelle-rich phase (%REM(LPS) > 98.00%). Therefore, this system can be exploited as the first step for purification in biotechnology processes for removal of higher LPS concentrations.
Asunto(s)
Biotecnología , Fraccionamiento Químico/métodos , Escherichia coli/metabolismo , Fermentación , Lipopolisacáridos/aislamiento & purificación , Escherichia coli/química , Escherichia coli/citología , Proteínas Fluorescentes Verdes/química , Lipopolisacáridos/química , Lipopolisacáridos/metabolismo , Micelas , Agua/químicaRESUMEN
Green fluorescent protein (GFP) shows remarkable structural stability and high fluorescence; its stability can be directly related to its fluorescence output, among other characteristics. GFP is stable under increasing temperatures, and its thermal denaturation is highly reproducible. Some polymers, such as polyethylene glycol, are often used as modifiers of characteristics of biological macromolecules, to improve the biochemical activity and stability of proteins or drug bioavailability. The aim of this study was to evaluate the thermal stability of GFP in the presence of different PEG molar weights at several concentrations and exposed to constant temperatures, in a range of 70-95 degrees C. Thermal stability was expressed in decimal reduction time. It was observed that the D-values obtained were almost constant for temperatures of 85, 90, and 95 degrees C, despite the PEG concentration or molar weight studied. Even though PEG can stabilize proteins, only at 75 degrees C, PEG 600 and 4,000 g/mol stabilized GFP.
Asunto(s)
Proteínas Fluorescentes Verdes/química , Polietilenglicoles/química , Temperatura , Peso Molecular , Estabilidad ProteicaRESUMEN
Green fluorescent protein (GFP) is an excellent biosensor as a result of its ability to be easily monitored in a wide variety of applications. Enzymes and proteins have been used as biological indicators to evaluate the immediate efficacy of industrial procedures, such as blanching, pasteurization, and disinfection treatments, as well as to monitor the satisfactory preservation of a product subjected to disinfection or sterilization. The purpose of this work was to study GFP stability in chlorinated water for injection (WFI) and chlorinated buffered solutions at various pH ranges, with and without agitation, to evaluate the exposure time required for chlorine to decrease 90% of its fluorescence intensity (decimal reduction time, D-value, min, 25 degrees C). Fluorescence intensity (Ex/Emmax = 394/509 nm) was measured immediately after the addition of GFP (8.0-9.0 microg/mL) into buffered or unbuffered chlorine solutions with or without constant stirring. With solutions constantly stirred, GFP fluorescence decreased abruptly on contact with chlorine in concentrations greater than 150 ppm, with D-values between 1.3 min (147 ppm chlorine) and 1.7 min (183 ppm chlorine). In phosphate buffered chlorine solutions (pH = 7.15 +/- 0.08), GFP retained its structure between 52 and 94 ppm, but protein stability decreased 10-fold when exposed to 110 ppm chlorine. The recovery of GFP fluorescence intensity due to renaturation was observed between 30 and 100 ppm chlorine in WFI (final pH = 11.01 +/- 0.23) without stirring. Stirring enhanced the contact between GFP and chlorine throughout the assay and provided a more accurate D-value evaluation. GFP performed as a suitable fluorescent marker for monitoring disinfection effectiveness.
Asunto(s)
Cloro/química , Proteínas Fluorescentes Verdes/química , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , SolucionesRESUMEN
BACKGROUND: Purified water for pharmaceutical purposes must be free of microbial contamination and pyrogens. Even with the additional sanitary and disinfecting treatments applied to the system (sequential operational stages), Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas alcaligenes, Pseudomonas picketti, Flavobacterium aureum, Acinetobacter lowffi and Pseudomonas diminuta were isolated and identified from a thirteen-stage purification system. To evaluate the efficacy of the chemical agents used in the disinfecting process along with those used to adjust chemical characteristics of the system, over the identified bacteria, the kinetic parameter of killing time (D-value) necessary to inactivate 90% of the initial bioburden (decimal reduction time) was experimentally determined. METHODS: Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas alcaligenes, Pseudomonas picketti, Flavobacterium aureum, Acinetobacter lowffi and Pseudomonas diminuta were called in house (wild) bacteria. Pseudomonas diminuta ATCC 11568, Pseudomonas alcaligenes INCQS , Pseudomonas aeruginosa ATCC 15442, Pseudomonas fluorescens ATCC 3178, Pseudomonas picketti ATCC 5031, Bacillus subtilis ATCC 937 and Escherichia coli ATCC 25922 were used as 'standard' bacteria to evaluate resistance at 25 degrees C against either 0.5% citric acid, 0.5% hydrochloric acid, 70% ethanol, 0.5% sodium bisulfite, 0.4% sodium hydroxide, 0.5% sodium hypochlorite, or a mixture of 2.2% hydrogen peroxide (H2O2) and 0.45% peracetic acid. RESULTS: The efficacy of the sanitizers varied with concentration and contact time to reduce decimal logarithmic (log10) population (n cycles). To kill 90% of the initial population (or one log10 cycle), the necessary time (D-value) was for P. aeruginosa into: (i) 0.5% citric acid, D = 3.8 min; (ii) 0.5% hydrochloric acid, D = 6.9 min; (iii) 70% ethanol, D = 9.7 min; (iv) 0.5% sodium bisulfite, D = 5.3 min; (v) 0.4% sodium hydroxide, D = 14.2 min; (vi) 0.5% sodium hypochlorite, D = 7.9 min; (vii) mixture of hydrogen peroxide (2.2%) plus peracetic acid (0.45%), D = 5.5 min. CONCLUSION: The contact time of 180 min of the system with the mixture of H2O2+ peracetic acid, a total theoretical reduction of 6 log10 cycles was attained in the water purified storage tank and distribution loop. The contact time between the water purification system (WPS) and the sanitary agents should be reviewed to reach sufficient bioburden reduction (over 6 log10).