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1.
Pharmaceutics ; 15(8)2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37631251

RESUMEN

BACKGROUND: Ursodeoxycholic acid (UDCA) is a therapeutic agent used for the treatment of cholestatic hepatobiliary diseases in pediatric patients. It is a bile acid that presents high lipophilicity, and it belongs to Class II of the Biopharmaceutical Classification System (BCS), which exhibits low water solubility and high intestinal permeability, which leads to poor oral absorption. The objective of this work was to design and optimize UDCA nanosuspensions by means of the precipitation-ultrasonication method to improve the solubility, dissolution, and oral bioavailability of UDCA. METHODS: A three-level, three-factor Box-Behnken design was used to optimize formulation variables and obtain uniform, small-particle-size UDCA nanosuspensions. The independent variables were: stabilizer percentage (X1), amplitude (X2), and sonication time (X3), and the dependent variable was the particle size (Y1). In the precipitation-ultrasonication method, UDCA was dissolved in acetone:PEG 400 (1:1 v/v) and quickly incorporated into the antisolvent (pre-cooled aqueous dispersion of HPMC E-15 0.3%), by means of intense sonication at 50 W for 5 min, controlling temperature through an ice water bath. The lyophilization efficacy was evaluated by means of a cryoprotective efficacy test, working with 10% maltose at -80 °C. The nanosuspensions were characterized by dynamic light scattering (DLS), X-ray diffraction, and scanning electron microscopy (SEM). The physicochemical stability was determined at 25 °C and 4 °C at 7, 14, 30, and 60 days, and the UDCA content was analyzed via HPLC-UV. An in vitro dissolution assay and an oral bioavailability study were performed in male Wistar rats. RESULTS: A significant impact was achieved in the optimized nanosuspension with 0.3% (stabilizer), 50 W (amplitude), and 5 min (sonication time), with a particle size of 352.4 nm, PDI of 0.11, and zeta potential of -4.30 mV. It presented adequate physicochemical stability throughout the study and the UDCA content was between 90% and 110%. In total, 86% of UDCA was dissolved in the in vitro dissolution test. The relative oral bioavailability was similar without significant statistical differences when comparing the lyophilized nanosuspension and the commercial tablet, the latter presenting a more erratic behavior. The pharmacokinetic parameters of the nanosuspension and the commercial tablet were Tmax (1.0 ± 0.9 h vs. 2.0 ± 0.8 h, respectively), Cmax (0.558 ± 0.118 vs. 0.366 ± 0.113 µM, respectively), ΔCmax (0.309 ± 0.099 vs. 0.232 ± 0.056, respectively), AUC (4.326 ± 0.471 vs. 2.188 ± 0.353 µg/mL.h, respectively, p < 0.02), and IAUC0-24h (2.261 ± 0.187 µg/mL.h vs. 1.924 ± 0.440 µg/mL.h, respectively). CONCLUSIONS: The developed nanosuspension presents an appropriate dosage and administration for pediatric patients. On the other hand, it exhibits an adequate absorption and UDCA oral bioavailability.

2.
Int J Pharm ; 634: 122656, 2023 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-36716829

RESUMEN

Supplementation with Coenzyme Q10 (CoQ10), in patients with its deficiency, has greater odds of success if the treatment is carried out early with an appropriate formulation. For neonatal CoQ10 deficiency, infant formula supplementation could be an attractive option. However, solid CoQ10 cannot be solubilized or dispersed in milk matrix leading to an inefficient CoQ10 dosage and poor intestinal absorption. We developed and characterized a high-dose CoQ10 oil-in-water (O/W) nanoemulsion suitable to supplement infant formula without modifying its organoleptic characteristics. CoQ10 powder and soy lecithin were solubilized in an oil phase consisted of Labrasol® and LabrafacTM. The aqueous phase was Tween 80, TPGS, methylparaben and propylparaben. O/W nanoemulsion was prepared by adding dropwise the oil phase to the aqueous phase under stirring to a final concentration of CoQ10 9.5 % w/w followed by ultrasonic homogenization. Pharmacotechnical parameters were determined. This formulation resulted to be easily to be dispersed in milk matrix, stable for at least 90 days, with no cytotoxicity in in vitro assays, and higher bioavailability than CoQ10 powder. CoQ10 nanoemulsion supplementation in the infant formula facilitates the individualized administration for the child with accurate dosage, overcome swallowing difficulties and in turn could increase the treatment adherence and efficacy.


Asunto(s)
Fórmulas Infantiles , Ubiquinona , Humanos , Recién Nacido , Disponibilidad Biológica , Suplementos Dietéticos , Polvos , Lactante
3.
Chem Biodivers ; 19(10): e202200565, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36048575

RESUMEN

Ligaria cuneifolia (Ruiz & Pav.) Tiegh (Loranthaceae) and Phoradendron liga (Gillies ex Hook. & Arn.) Eichler (Santalaceae) are regarded as Argentine mistletoes based on their similarities with the European counterpart, Viscum album L. (Santalaceae). These two species are the most used medicinal plants to treat high blood pressure in the Argentinian population. To provide scientific grounds to their traditional use and therapeutic potential, they were selected as herbal drug candidates. The main findings would support the anti-hypertensive action, the anticholesterolemic and antioxidant features of L. cuneifolia, and immunomodulatory properties for both species. Quercetin-O-glycosides, galloyl glycosides, and proanthocyanidins are present in L. cuneifolia while P. liga shows C-glycosyl flavones and 3-deoxyproanthocyanidins. This review summarizes the phytochemical characterization, medicinal properties and reveals promising results warranting future efforts for further investigation.


Asunto(s)
Flavonas , Loranthaceae , Phoradendron , Proantocianidinas , Santalaceae , Loranthaceae/química , Quercetina , Antioxidantes/farmacología , Antihipertensivos , Extractos Vegetales/química , Glicósidos/farmacología
4.
Pharm Dev Technol ; 26(5): 599-609, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33759695

RESUMEN

Ursodeoxycholic acid (UDCA) is used in the oral therapy of hepatobiliary cholestatic diseases. Due to UDCA low aqueous solubility, two pediatric oral suspensions (25 mg/mL) were formulated with a few excipients, suspension A (SA) and suspension B (SB) with a vehicle, including two suspending agents. Physical, chemical and microbiological stability and a rheological study were performed at three different conditions (5 °C ± 3 °C, 25 °C ± 2 °C/60% RH ± 5% RH and 40 °C ± 2 °C/75% RH ± 5% RH) for 120 days. Moreover, dissolution study, content uniformity, related substances, and a study of relative oral bioavailability were also carried out. Both suspensions were physically, chemically and microbiologically stable throughout the study. SA and SB can be stored at 25 °C and 5 °C for at least 120 days whereas SA can be kept at 40 °C for at least 90 days and SB for 120 days. They both met USP specifications for dissolution, content uniformity, and related substances. SA and SB showed an improved relative oral bioavailability compared to the solid dosage form and they both displayed similar relative oral bioavailability with no significant differences between them. The developed suspensions proved to be safe and adequate and they are ideal for pediatric use for their acceptability, accurate dose administration and treatment adherence.


Asunto(s)
Colagogos y Coleréticos/administración & dosificación , Excipientes/química , Ácido Ursodesoxicólico/administración & dosificación , Administración Oral , Animales , Disponibilidad Biológica , Química Farmacéutica , Colagogos y Coleréticos/química , Colagogos y Coleréticos/farmacocinética , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humedad , Masculino , Ratas , Ratas Sprague-Dawley , Reología , Solubilidad , Suspensiones , Temperatura , Ácido Ursodesoxicólico/química , Ácido Ursodesoxicólico/farmacocinética
5.
Hosp Pharm ; 55(5): 314-322, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32999501

RESUMEN

Objectives: To develop and to study the physicochemical and microbiological stability of omeprazole liquid oral formulations used as therapeutic agent in many acid-related disorders, for pediatric use. Furthermore, to optimize and validate a stability-indicating high-performance liquid chromatography (HPLC) method for the analysis of omeprazole in the studied formulations. Method: Oral liquid suspensions of omeprazole were prepared at 2 mg/mL using crushed omeprazole pellets (formulation A) and pure omeprazole (formulation B) with a complete vehicle including humectant, suspending, sweetening, antioxidant, and flavoring agents. Samples were stored at 4°C and 25°C. Omeprazole content of each formulation was analyzed in triplicate using micro-HPLC at 0, 3, 7, 14, 30, 60, 90, 120, and 150 days. Other parameters were also determined, such as appearance, pH, resuspendibility, and viscosity. Microbiological studies were conducted according to the United Stated Pharmacopeia (USP) guidelines for non-sterile products. Results: Formulation A stayed physicochemical and microbiologically stable at refrigerated (4°C) conditions during at least 150 days and it only stayed stable during 14 days at 25°C. Formulation B was stayed physicochemical and microbiologically stable at refrigerated (4°C) conditions at least 90 days, but it is not recommended to store at 25°C for more than 1 day. Conclusions: Formulation A and formulation B can be stored for at least 150 and 90 days, respectively, at refrigerated conditions. Formulation A can be stored at room temperature for 14 days. Both formulations are perfectly suitable for pediatric patients who are usually notable to swallow solid oral formulations. The proposed analytical method was suitable for the study of stability of different formulations.

6.
Chem Biodivers ; 17(10): e2000302, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32725761

RESUMEN

Ligaria cuneifolia (Ruiz & Pav.) Tiegh. (Loranthaceae), the 'Argentine mistletoe', is a hemiparasite species largely used in folk medicine. The aim of this study was to evaluate the antioxidant activity using in vitro, ex vivo, and in vivo methods. A screening of phenolics was performed by UV spectroscopy on different fractions. The antioxidant capacity was evaluated in vitro by the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH. ) assay on a crude extract (CE), ethyl acetate fraction (EAF), and aqueous fraction (AF). The results suggest that EAF concentrates the antioxidant capacity and was selected for further analysis. Capillary electrophoresis was employed to monitor the individual antioxidant capacity and the potential contributors to this effect. Ex vivo assays showed an efficient inhibition of tert-butyl hydroperoxide-induced rat liver phospholipid oxidation, as well as rat brain autoxidation, and H2 O2 -induced DNA damage in blood monocytes. In vivo, the topical application of EAF significantly decreased skin chemiluminescence in a mice model.


Asunto(s)
Antioxidantes/farmacología , Flavonoides/farmacología , Loranthaceae/química , Fosfolípidos/antagonistas & inhibidores , Extractos Vegetales/farmacología , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Argentina , Compuestos de Bifenilo/antagonistas & inhibidores , Daño del ADN , Femenino , Flavonoides/química , Flavonoides/aislamiento & purificación , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Oxidación-Reducción , Fosfolípidos/metabolismo , Picratos/antagonistas & inhibidores , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas Sprague-Dawley , terc-Butilhidroperóxido/antagonistas & inhibidores , terc-Butilhidroperóxido/farmacología
7.
Eur J Pharmacol ; 882: 173270, 2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-32534074

RESUMEN

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease characterized by pruritus, elevated serum bile acids and abnormal liver function that may be associated with severe adverse pregnancy outcomes. We previously reported that plasma coenzyme Q10 (CoQ10) is decreased in women with ICP as it is its analogue coenzyme Q9 (CoQ9) in rats with ethinyl estradiol (EE)-induced cholestasis. The aim of the present study was to evaluate the possible therapeutic role of CoQ10 in experimental hepatocellular cholestasis and to compare it with ursodeoxycholic acid (UDCA) supplementation. Bile acids, CoQ9, CoQ10, transaminases, alkaline phosphatase, retinol, α-tocopherol, ascorbic acid, thiobarbituric acid reactive substances, carbonyls, glutathione, superoxide dismutase and catalase were assessed in plasma, liver and/or hepatic mitochondria in control and cholestatic rats supplemented with CoQ10 (250 mg/kg) administered alone or combined with UDCA (25 mg/kg). CoQ10 supplementation prevented bile flow decline (P < 0.05) and the increase in serum alkaline phosphatase and bile acids, particularly lithocholic acid (P < 0.05) in cholestatic rats. Furthermore, it also improved oxidative stress parameters in the liver, increased both CoQ10 and CoQ9 plasma levels and partially prevented the fall in α-tocopherol (P < 0.05). UDCA also prevented cholestasis, but it was less efficient than CoQ10 to improve the liver redox environment. Combined administration of CoQ10 and UDCA resulted in additive effects. In conclusion, present findings show that CoQ10 supplementation attenuated EE-induced cholestasis by promoting a favorable redox environment in the liver, and further suggest that it may represent an alternative therapeutic option for ICP.


Asunto(s)
Colestasis Intrahepática/tratamiento farmacológico , Suplementos Dietéticos , Complicaciones del Embarazo/tratamiento farmacológico , Ubiquinona/análogos & derivados , Animales , Catalasa/metabolismo , Colestasis Intrahepática/metabolismo , Femenino , Glutatión/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Embarazo , Complicaciones del Embarazo/metabolismo , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Ubiquinona/farmacología , Ubiquinona/uso terapéutico , Ácido Ursodesoxicólico/uso terapéutico
8.
Int J Pharm ; 582: 119315, 2020 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-32283195

RESUMEN

Coenzyme Q10 (CoQ10) is essential in mitochondrial bioenergetics and is a potent endogenous antioxidant. Low CoQ10 levels are associated with neurodegenerative, metabolic, muscular and cardiovascular disorders. Early treatment with high doses (5-50 mg/kg/day) demonstrated to limit the onset and progression of neuropathology. Recently, we developed an oleogel matrix able to support a high dose of oil-dissolved CoQ10, easy to swallow by CoQ10-deficient patients who suffer from secondary dysphagia. In the present study, we evaluated the bioavailability of oleogel-dissolved CoQ10 and plasma antioxidant status in healthy adults in single-dose and repeated-dose studies. The single-dose study demonstrated that, in terms of CoQ10 bioavailability, 1 g CoQ10/5g oleogel-disk was equivalent to the solid form (1 g CoQ10/three 00-size-capsules), whereas the repeated-dose study (14-days-administration) demonstrated a significantly higher increase in plasma CoQ10 when administered through the oleogel, which could be compatible with the levels necessary to achieve an adequate therapeutic response. Also, a trend to a higher plasma apparent half-life (greater than24 h) was observed for the oleogel-loaded-CoQ10. In conclusion, the oleogel matrix does not compromise the oil-dissolved CoQ10 bioavailability and can prevent the non-adherence to this vital supplementation in patients with high CoQ10 requirements. No significant variation in the plasma antioxidant status (vitamins A, E and C, glutathione and TBARs) was observed.


Asunto(s)
Antioxidantes/administración & dosificación , Portadores de Fármacos , Ubiquinona/análogos & derivados , Administración Oral , Adulto , Antioxidantes/química , Antioxidantes/farmacocinética , Disponibilidad Biológica , Biomarcadores/sangre , Cápsulas , Estudios Cruzados , Composición de Medicamentos , Femenino , Semivida , Humanos , Masculino , Persona de Mediana Edad , Compuestos Orgánicos/química , Ubiquinona/administración & dosificación , Ubiquinona/química , Ubiquinona/farmacocinética
9.
Plant Physiol Biochem ; 151: 411-420, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32283507

RESUMEN

Glycerophospholipids (GPLs) from cell membranes (CM) are a proper source for the synthesis of lipid messengers able to activate signal pathways that will define the plant survival under changing and stressful environmental conditions. Little is known about how GPLs metabolism (GPLsM) is regulated and the effects of phenol treatment on GPLs composition. In this work, we studied the effects of phenol both on GPLs turnover and on the expression of GPLsM-related genes potentially regulated by the circadian clock, using tobacco hairy root cultures (HRC). Phenol decreased the total PC levels and increased PE, PG and CL levels in the dark phase. Different molecular species of PC and PE showed the same trend than the total PC and PE upon phenol treatment. Besides, significant differences in the expression of all studied genes related to GPLsM were found. NtCCT2 expression was affected at all analyzed times while NtPECT1 and NtAAPT1 showed similar expression patterns. NtCDS1, NtPGPS2 and NtCLS genes showed significant and differential expression profiles both in untreated and treated HRC. PECT1 and NtPGPS2 genes seem to conserve a circadian expression profile mainly in untreated HRC. However, phenol was able to modify the GPLs composition and the expression of genes related to GPLs synthesis. The GPLs modification could be explained by the up-regulation of NtPECT1, NtAAPT1 and NtCLS genes during the dark phase, suggesting for being a crucial moment for HRC to trigger an adaptive response against this organic pollutant.


Asunto(s)
Relojes Circadianos , Nicotiana , Fenol , Raíces de Plantas , Relojes Circadianos/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Glicerofosfolípidos/metabolismo , Fenol/toxicidad , Raíces de Plantas/efectos de los fármacos , Nicotiana/efectos de los fármacos
10.
Clin Res Hepatol Gastroenterol ; 44(3): 368-374, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31477533

RESUMEN

AIM: Intrahepatic cholestasis of pregnancy (ICP) is considered a high-risk condition because it may have serious consequences for the fetus health. ICP is characterized by the accumulation of bile acids in maternal serum which contribute to an imbalance between the production of reactive oxygen species and the antioxidant defenses increasing the oxidative stress experienced by the fetus. Previously, it was reported a significant decrease in plasma coenzyme Q10 (CoQ10) in women with ICP. CoQ10 is a redox substance integrated in the mitochondrial respiratory chain and is recognized as a potent antioxidant playing an intrinsic role against oxidative damage. The objective of the present study was to investigate the levels of CoQ10 in umbilical cord blood during normal pregnancy and in those complicated with ICP, all of them compared to the maternal ones. METHODS: CoQ10 levels and bile acid levels in maternal and umbilical cord blood levels during normal pregnancies (n=23) and in those complicated with ICP (n=13), were investigated. RESULTS: A significant decrease in neonate CoQ10 levels corrected by cholesterol (0.105±0.010 vs. 0.069±0.011, P<0.05, normal pregnancy vs. ICP, respectively), together with an increase of total serum bile acids (2.10±0.02 vs. 7.60±2.30, P<0.05, normal pregnancy vs. ICP, respectively) was observed. CONCLUSIONS: A fetus from an ICP mother is exposed to a greater risk derived from oxidative damage. The recognition of CoQ10 deficiency is important since it could be the starting point for a new and safe intervention strategy which can establish CoQ10 as a promising candidate to prevent the risk of oxidative stress.


Asunto(s)
Ataxia/sangre , Ácidos y Sales Biliares/sangre , Colestasis Intrahepática/sangre , Sangre Fetal/química , Enfermedades Mitocondriales/sangre , Debilidad Muscular/sangre , Complicaciones del Embarazo/sangre , Ubiquinona/análogos & derivados , Ubiquinona/deficiencia , Adulto , Ataxia/diagnóstico , Biomarcadores/sangre , Peso al Nacer , Colesterol/sangre , Ácido Cólico/sangre , Estudios Transversales , Femenino , Feto/metabolismo , Edad Gestacional , Humanos , Recién Nacido , Enfermedades Mitocondriales/diagnóstico , Debilidad Muscular/diagnóstico , Oxidación-Reducción , Estrés Oxidativo , Embarazo , Estudios Prospectivos , Especies Reactivas de Oxígeno/metabolismo , Ubiquinona/sangre , Adulto Joven
11.
Future Med Chem ; 11(14): 1791-1810, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31368345

RESUMEN

Dendrimers are synthetic polymers that grow in three dimensions into well-defined structures. Their morphological appearance resembles a number of trees connected by a common point. Dendritic nanoparticles have been studied for a large number of pharmaceutical and biomedical applications including gene and drug delivery, clinical diagnosis and MRI. Despite the application of dendrimers, research is still in its childhood in comparison with liposomes and other nanomaterials. They are now playing a key role in several therapeutic strategies, with dendrimer-based products in clinical trials. The aim of this review is to describe the state-of-the-art of biomedical applications of dendrimers - and dendrimer conjugates - such as drug and gene delivery and antiviral activity.


Asunto(s)
Antivirales/química , Dendrímeros/química , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Animales , Antivirales/farmacología , Técnicas de Transferencia de Gen , Humanos , Virus/efectos de los fármacos
12.
Electrophoresis ; 40(12-13): 1719-1721, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30977529

RESUMEN

A simple and highly sensitive CE-UV method was applied in the determination of l-ctrulline, which was developed from an oral formulation for pediatric use. The novel method was based on the analysis of l-citrulline for direct ultraviolet detection at 198 nm. The BGE consisted of 10 mM sodium tetraborate and 50 mM SDS at pH 9, and the electrophoretic parameters were optimized. The method was validated in terms of specificity, linearity, LOD, LOQ, precision, accuracy, and robustness. The LOD and LOQ obtained were 1.36 and 4.54 µg/mL, respectively. In addition, the method offers higher sensitivity and specificity compared with the results obtained from HPLC method using UV-detectors, in which l-citrulline needs to be derivatizated. Furthermore, low cost and simplicity of the system allowed the rapid and simple quantitation of l-citrulline in the oral formulation for quality control and stability indicated method.


Asunto(s)
Citrulina/análisis , Electroforesis Capilar/métodos , Soluciones Farmacéuticas/análisis , Espectrofotometría Ultravioleta/métodos , Cromatografía Capilar Electrocinética Micelar , Citrulina/química , Límite de Detección , Modelos Lineales , Soluciones Farmacéuticas/química , Reproducibilidad de los Resultados
13.
Artículo en Inglés | MEDLINE | ID: mdl-30953919

RESUMEN

Coenzyme Q10 (CoQ10) is an important cofactor in the mitochondrial respiratory chain and a potent endogenous antioxidant. CoQ10 deficiency is currently associated with numerous diseases like mitochondrial and neurodegenerative pathologies, in which the earliest diagnosis and treatment with CoQ10 supplementation becomes paramount for patient's treatment. Consequently, the determination of CoQ10 levels in different biological matrices positions as a fundamental tool. Urine is an attractive and non-invasive alternative source to tissue, blood or other biofluids for CoQ10 analysis. However, it poses an analytical challenge, as it generally requires a complex sample preparation, with multiple steps. In this work we developed and validated a molecularly imprinted polymer solid phase extraction (MIP-SPE) followed by a HPLC-MS/MS method for the analysis of CoQ10 in urine. The MIP-SPE method developed is simple and fast compared to previously traditional reported methods, with reduced processing time, improved sample cleaning and excellent recovery values, along with its inherent high selectivity. The developed chromatographic method was validated according to FDA guidelines, and demonstrated to be suitable for the analysis of CoQ10 in urine samples with LOQ and LOD values of 0.6 ng/mL and 0.2 ng/mL of CoQ10 in urine respectively. Recovery values at three concentration levels were higher than 90.0%.The proposed method is amenable to be applied in pediatric patients due to the low sample requirement and useful for diagnosis and post-treatment control.


Asunto(s)
Impresión Molecular/métodos , Extracción en Fase Sólida/métodos , Ubiquinona/análogos & derivados , Adolescente , Adulto , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Límite de Detección , Modelos Lineales , Masculino , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem , Ubiquinona/aislamiento & purificación , Ubiquinona/orina , Adulto Joven
14.
Int J Pharm ; 556: 9-20, 2019 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-30529659

RESUMEN

Coenzyme Q10 (CoQ10) is a mitochondrial respiratory cofactor and potent endogenous antioxidant. In CoQ10-deficient patients, early treatment with high-oral doses (5-50 mg/kg/day) can limit the progression of renal disease and the onset of neurological manifestations. Crystalline CoQ10 is lipophilic, water-insoluble, and poorly absorbed in the gut. Here, CoQ10 showed low bulk density, another important disadvantage in solid oral formulations. Thus, we propose the use of oleogels to maintain dissolved a high-dose of CoQ10 in medium-chain triglyceride (MCT) oil, using ethylcellulose (EC) for gelling, and a surfactant (sorbitan monostearate -SMS- or lecithin). "True gels" were only obtained with the surfactant presence. Thermoreversible oleogels with 1 g of dissolved CoQ10 per 5 g-disk were successfully developed with proved stability and solubility for 12 months (25.0 °C). SMS was better than lecithin as a surfactant because it allowed lower syneresis, higher CoQ10 retention for 12 months, and notably higher oxidative-stability of the MCT-oil, best immobilized by its true gel network. Plastic deformation without fracture was determined under compression, emulating the soft deformation behavior inside the mouth. SMS-oleogels allowed loading a maximal solubilized CoQ10 dose with maximal stability, and may be easier to swallow by CoQ10-deficient patients who suffer from secondary dysphagia.


Asunto(s)
Antioxidantes/administración & dosificación , Celulosa/análogos & derivados , Tensoactivos/química , Ubiquinona/análogos & derivados , Administración Oral , Antioxidantes/química , Celulosa/química , Química Farmacéutica/métodos , Relación Dosis-Respuesta a Droga , Estabilidad de Medicamentos , Hexosas/química , Lecitinas/química , Compuestos Orgánicos , Solubilidad , Triglicéridos/química , Ubiquinona/administración & dosificación , Ubiquinona/química
15.
Electrophoresis ; 39(4): 616-619, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29110333

RESUMEN

A simple, highly sensitive, and robust CE method applied to the determination of alendronate (ALN) was developed from matrices for tissue engineering, characterized by being highly complex systems. The novel method was based on the ALN derivatization with o-phthalaldehyde and 2-mercaptoethanol for direct ultraviolet detection at 254 nm. The BGE consisted of 20 mM sodium borate buffer at pH 10, and the electrophoretic parameters were optimized.The method was validated in terms of specificity, linearity, LOD, LOQ, precision, accuracy, and robustness. The LOD and LOQ obtained were 0.8 and 2.7 µg/mL, respectively. In addition, the method offers higher sensitivity and specificity compared to other CE and HPLC methods using UV-detectors, as well as low cost and simplicity that allowed the rapid and simple quantitation of ALN from bone regeneration matrices.


Asunto(s)
Alendronato/análisis , Portadores de Fármacos/química , Electroforesis Capilar/métodos , Espectrofotometría Ultravioleta/métodos , Alendronato/farmacocinética , Materiales Biocompatibles , Límite de Detección , Modelos Lineales , Reproducibilidad de los Resultados
16.
Electrophoresis ; 38(9-10): 1292-1300, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28090664

RESUMEN

The present work deals with the development and validation of a novel dual CD-MEKC system for the systematic flavonoid fingerprinting of Ligaria cuneifolia (R. et P.) Tiegh.-Loranthaceae-extracts. The BGE consisted of 20 mM pH 8.3 borate buffer, 50 mM SDS, a dual CD system based on the combination of 5 mM ß-CD and 2% w/v S-ß-CD, and 10% v/v methanol. The proposed method has been successfully applied to the comparative analysis of extracts from aerial parts and different hosts, geographical areas, and extraction procedures in order to establish the flavonoid fingerprint of L. cuneifolia. The method was validated according to international guidelines. LOD and LOQ, intra and interday precision, and linearity were determined for catechin, epicatechin, procyanidin B2, rutin, quercetin-3-O-glucoside, quercetin-3-O-xyloside, quercetin-3-O-rhamnoside, quercetin-3-O-arabinofuranoside, quercetin-3-O-arabinopyranoside, and quercetin. The CD-MEKC methodology emerges as a suitable alternative to the traditional HPLC for quality control, fingerprinting, and standardization of L. cuneifolia extracts from different sources.


Asunto(s)
Cromatografía Capilar Electrocinética Micelar/métodos , Flavonoides/análisis , Loranthaceae/química , Extractos Vegetales/química , Límite de Detección , Modelos Lineales , Reproducibilidad de los Resultados
17.
J Pharm Pharmacol ; 69(5): 567-573, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27464712

RESUMEN

OBJECTIVES: Conduct a preliminary comparison of the bioavailability between two formulations: commercial grade coenzyme Q10 (CoQ10) powder (solid formulation) and a new oil-in-water liquid emulsion and their effect on other antioxidants. METHODS: Six healthy individuals participated in a randomized, crossover, open, consecutive design, with a 2-week washout period. Pharmacokinetic parameters were assessed after a single and multiple intakes of 250 mg CoQ10 given daily for 1 week. KEY FINDINGS: The differences in the pharmacokinetic parameters of maximum plasma concentration, area under the curve between 0-360 and 0-4 h, elimination half-life were statistically significant with a relative bioavailability of 489% increase over solid CoQ10 formulation. A multiple dose supplementation increased plasma CoQ10 levels in both formulations, liquid emulsion performing better (2.4- vs 3.9-fold for solid and liquid formulation, respectively) without modifications on other antioxidants. Furthermore, the plasma CoQ10 at 7th day was statistically different between formulations (P < 0.05). CONCLUSIONS: The results obtained showed that liquid emulsion improves the bioavailability of CoQ10 respect to solid form which not only facilitates the individualized administration for the child but in turn could increase the therapeutic efficacy, which should be confirmed by further studies.


Asunto(s)
Ubiquinona/análogos & derivados , Adolescente , Adulto , Antioxidantes/farmacocinética , Disponibilidad Biológica , Química Farmacéutica/métodos , Estudios Cruzados , Suplementos Dietéticos , Emulsiones/farmacocinética , Femenino , Semivida , Humanos , Masculino , Medicina de Precisión/métodos , Ubiquinona/metabolismo , Ubiquinona/farmacocinética , Adulto Joven
18.
Biomed Mater ; 11(6): 065003, 2016 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-27767020

RESUMEN

Novel multifunctional nanocomposite scaffolds made of nanobioactive glass and alginate crosslinked with therapeutic ions such as calcium and copper were developed for delivering therapeutic agents, in a highly controlled and sustainable manner, for bone tissue engineering. Alendronate, a well-known antiresorptive agent, was formulated into microspheres under optimized conditions and effectively loaded within the novel multifunctional scaffolds with a high encapsulation percentage. The size of the cation used for the alginate crosslinking impacted directly on porosity and viscoelastic properties, and thus, on the degradation rate and the release profile of copper, calcium and alendronate. According to this, even though highly porous structures were created with suitable pore sizes for cell ingrowth and vascularization in both cases, copper-crosslinked scaffolds showed higher values of porosity, elastic modulus, degradation rate and the amount of copper and alendronate released, when compared with calcium-crosslinked scaffolds. In addition, in all cases, the scaffolds showed bioactivity and mechanical properties close to the endogenous trabecular bone tissue in terms of viscoelasticity. Furthermore, the scaffolds showed osteogenic and angiogenic properties on bone and endothelial cells, respectively, and the extracts of the biomaterials used promoted the formation of blood vessels in an ex vivo model. These new bioactive nanocomposite scaffolds represent an exciting new class of therapeutic cell delivery carrier with tunable mechanical and degradation properties; potentially useful in the controlled and sustainable delivery of therapeutic agents with active roles in bone formation and angiogenesis, as well as in the support of cell proliferation and osteogenesis for bone tissue engineering.


Asunto(s)
Huesos/fisiología , Nanocompuestos/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Alendronato/química , Alginatos/química , Animales , Materiales Biocompatibles/química , Células de la Médula Ósea/citología , Resorción Ósea , Calcio/química , Supervivencia Celular , Membrana Corioalantoides/metabolismo , Fuerza Compresiva , Cobre/química , Coturnix , Reactivos de Enlaces Cruzados/química , Elasticidad , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Células Madre Mesenquimatosas/citología , Microesferas , Osteogénesis , Porosidad , Ratas , Ratas Sprague-Dawley , Estrés Mecánico , Viscosidad
19.
Electrophoresis ; 37(17-18): 2420-8, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27524401

RESUMEN

A stereoselective CD-MEKC system has been developed for the quality control of Montelukast (MK), commercialized as a pure enantiomer. The proposed method is the first one that allows the simultaneous determination of MK, its enantiomeric form, diasteroisomers and its main degradation compound (MK sulphoxide). CD-MEKC system is composed of 10 mM SDS, 10 mM sulfobutylether-ß-CD, 10 mM TM-ß-CD, and 20 mM borate buffer at pH 9.0. Combination of these two CDs allows high baseline enantioresolution between MK and its enantiomeric impurity, but also, between the diasteroisomeric forms. Moreover, a multivariate design was applied to optimize operational parameters. The method was designed to meet with requirements of the official pharmacopoeias and fully validated according to international guidelines. Linearity of MK was demonstrated in the range from 10.0 to 100.0 µg/mL (r(2) = 0.9908) with a LOD and LOQ of 0.30 and 0.90 µg/mL, respectively. Intra and interday precision were evaluated and RSD values were below 2%, and also, accuracy expressed as percentage of recovery was in a range from 99.0 to 101.9 for the three assayed levels. The method allows determining 0.02% w/w of the enantiomeric and diasteroisomeric impurities, and 0.01% w/w of MK sulphoxide. Robustness was evaluated by a Plackett and Burman design. Finally, the CD-MEKC system was successfully applied to the determination of related substances in MK bulk drug and its quantification in two pediatric pharmaceutical dosage forms.


Asunto(s)
Acetatos/análisis , Electroforesis Capilar/métodos , Antagonistas de Leucotrieno/análisis , Quinolinas/análisis , Ciclopropanos , Límite de Detección , Estándares de Referencia , Reproducibilidad de los Resultados , Estereoisomerismo , Sulfuros
20.
J Chromatogr A ; 1456: 1-9, 2016 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-27317007

RESUMEN

Molecularly imprinted polymer nanoparticles (MIPNPs) with the ability to recognize coenzyme Q10 (CoQ10) were synthesised in order to be employed as sorbent in a dispersive micro-solid phase extraction (DMSPE) for the determination of CoQ10 in a liver extract. CoQ10 is a redox-active, lipophilic substance integrated in the mitochondrial respiratory chain which acts as an electron carrier, shuttling electrons from complex I (NADH-ubiquinone oxidoreductase) and II (succinate-ubiquinone oxidoreductase) to complex III (ubiquinol-cytochrome c reductase), for the production of cellular energy. The MIPNPs were synthesised by precipitation polymerization using coenzyme Q0 as the dummy template, methacrylic acid as the functional monomer, an acetonitrile: water mixture as the porogen, ethylene glycol dimethacrylate as the crosslinker and potassium persulfate as initiator. The nanoparticles were characterized by microscopy, capillary electrophoresis, dynamic light scattering, N2 adsorption-desorption isotherms, and infrared spectroscopy. The MIPNPs demonstrated the presence of selective cavities complementary to the quinone nucleus of CoQ10, leading to a specific recognition of CoQ10 compared with related compounds. In the liver extract the relative CoQ10 peak area (CoQ10 area/total peak area) increased from 4.6% to 25.4% after the DMSPE procedure. The recovery percentage of CoQ10 from the liver matrix was between 70.5% and 83.7% quantified against CoQ10 standard processed under the same conditions. The DMSPE procedure allows the elution of almost all the CoQ10 retained (99.4%) in a small volume (200µL), allowing the sample to be concentrated 2.5 times (LOD: 1.1µgg(-1) and LOQ: 3.7µgg(-1) of tissue). The resulted clean up of the sample, the improvement in peak shape and baseline and the reduction of interferences, evidence that the MIPNPs could potentially be applied as sorbent in a DMSPE with satisfactory results and with a minimum amount of sorbent (1mg).


Asunto(s)
Reactivos de Enlaces Cruzados/química , Metacrilatos/química , Ácidos Polimetacrílicos/química , Extracción en Fase Sólida/métodos , Ubiquinona/análogos & derivados , Adsorción , Animales , Bovinos , Hígado/química , Impresión Molecular , Nanopartículas , Polimerizacion , Ácidos Polimetacrílicos/síntesis química , Ubiquinona/química , Ubiquinona/aislamiento & purificación
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