Asunto(s)
Humanos , Masculino , Adolescente , Enfermedades Autoinmunes/inducido químicamente , Azatioprina/efectos adversos , Hepatitis Autoinmune , Dermatosis Bullosa IgA Lineal/inducido químicamente , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológicoRESUMEN
Topical glucocorticoids (TG) such as dexamethasone (DEX) have been used for decades for the treatment of skin diseases. However, TG present well-documented side effects and their delivery to the skin is often insufficient. Therefore, many efforts have been undergone to improve the amount of drug delivered to the skin and to reduce side effects at the same time. In this work, the feasibility of DEX-submicron polymeric particles (SP) prepared by vibrational spray-drying as an approach to overcome the challenges associated with the topical administration of this drug class was evaluated. DEX was homogeneously dispersed in the SP matrix, according to confocal Raman microscopy analysis. Drug-loaded SP were incorporated into the oil phase of oil-in-water emulsions (creams). The formulation containing polymeric submicron particles (C-SP) showed controlled drug release kinetics and a significant drug accumulation in skin compared to formulations containing non-polymeric particles or free drug. DEX accumulation in the stratum corneum was evaluated by tape stripping and a depot effect over time was observed for C-SP, while the formulation containing the free drug showed a decrease over time. Similarly, C-SP presented higher drug retention in epidermis and dermis in skin penetration studies performed on pig skin in Franz diffusion cells, while drug permeation into the receptor compartment was negligible. It was demonstrated, for the first time, the advantageous application of submicron polymeric particles obtained by vibrational spray-drying in semisolid formulations for cutaneous administration to overcome challenges related to the therapy with TG such as DEX.
Asunto(s)
Dexametasona/administración & dosificación , Portadores de Fármacos/química , Glucocorticoides/administración & dosificación , Polímeros/química , Absorción Cutánea , Piel/metabolismo , Animales , Dexametasona/farmacocinética , Composición de Medicamentos/métodos , Liberación de Fármacos , Emulsiones , Glucocorticoides/farmacocinética , Técnicas In Vitro , Microscopía Confocal , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Piel/efectos de los fármacos , Propiedades de Superficie , Sus scrofa , Distribución Tisular , VibraciónRESUMEN
We developed a dermatological nanomedicine containing clobetasol propionate-loaded nanocapsules and evaluated its efficacy in a model of contact dermatitis after topical administration in rats. Hydrogels containing clobetasol propionate-loaded lipid-core nanocapsules or nanoemulsion (HG-CP-NC and HG-CP-NE, respectively) were prepared to evaluate the influence of the polymeric wall. They presented adequate pH values (5.50-6.50) and drug content (0.5 mg g(-1)) and their rheograms exhibited a non-Newtonian pseudoplastic behavior. The best in vitro drug release control was obtained for HG-CP-NC (1.03±0.11 µg cm(-2) h) compared to the HG-CP-NE (1.65±0.19 µg cm(-2) h) and the hydrogels containing nonencapsulated drug (HG-CP) (2.79±0.22 µg cm(-2) h). A significant increase in NTPDase activity was observed in lymphocytes for the group treated with 0.05% HG-CP-NC every other day compared to the group treated with 0.05% HG-CP every day using the in vivo model of contact dermatitis. The nanoencapsulation of clobetasol in nanocapsules led to a better control of the drug release from the semisolid nanomedicine and provided better in vivo dermatological efficacy.
Asunto(s)
Clobetasol/administración & dosificación , Clobetasol/química , Dermatitis por Contacto/tratamiento farmacológico , Nanocápsulas/administración & dosificación , Nanocápsulas/química , Administración Tópica , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Femenino , Hidrogeles/administración & dosificación , Hidrogeles/química , Concentración de Iones de Hidrógeno , Linfocitos/efectos de los fármacos , Nanomedicina/métodos , Tamaño de la Partícula , Ratas , Ratas WistarRESUMEN
The aim of the present work was to evaluate the feasibility to convert drug-loaded nanocapsule suspensions in a solid dosage form (tablets). Dexamethasone was used as a model drug due to its low aqueous solubility and fast drug release from conventional tablets. Granules containing dexamethasone-loaded nanocapsules were obtained by a wet granulation process using a dispersion of polyvinylpirrolidone/nanocapsules as a binder system. Granules were compressed in an eccentric compression machine (D-NC-T). A control formulation (tablets without nanocapsules) was also prepared (D-T). Tablets were characterized by means of mean weight, hardness, friability, diameter, thickness, disintegration time, drug content, morphological analysis by scanning electron microscopy (SEM), and in vitro drug release studies. D-NC-T showed adequate physicochemical characteristics according to the pharmacopeial requirements in terms of mean weight, hardness, friability, disintegration time and drug content. Intact nanocapsules in tablets were observed by SEM. In vitro drug release studies showed a slower release of dexamethasone from these tablets (D-NC-T) compared to the control formulation (D-T). Results showed that these tablets represent an interesting platform to the development of oral drug delivery systems containing polymeric nanocapsules.
Asunto(s)
Nanocápsulas/química , Comprimidos/química , Administración Oral , Química Farmacéutica/métodos , Dexametasona/administración & dosificación , Dexametasona/farmacocinética , Sistemas de Liberación de Medicamentos , Humanos , Técnicas In Vitro , Microscopía Electrónica de Rastreo , Nanocápsulas/ultraestructura , Nanotecnología , Polímeros/química , Povidona/químicaRESUMEN
CONTEXT: Our group previously reported the development of dexamethasone-loaded polymeric nanocapsules as an alternative for topical dermatological treatments. OBJECTIVE: Our study aimed to prepare and characterize a hydrogel containing this system to improve the effectiveness of the glucocorticoid for cutaneous disorders. METHODS: For the antiproliferative activity assay, a dexamethasone solution and D-NC were tested on Allium cepa root meristem model. D-NC were prepared by the interfacial deposition of preformed polymer. Hydrogels were prepared using Carbopol Ultrez 10 NF, as polymer, and characterized according to the following characteristics: pH, drug content, spreadability, viscosity, and in vitro drug release. RESULTS AND DISCUSSION: Nanocapsules showed mean particle size and zeta potential of 201 +/- 6 and -5.73 +/- 0.42 nm, respectively. They demonstrated a lower mitotic index (4.62%) compared to free dexamethasone (8.60%). Semisolid formulations presented acidic pH values and adequate drug content (between 5.4% and 6.1% and 100% and 105%, respectively). The presence of nanocapsules in hydrogels led to a decrease in their spreadability factor. Intact nanoparticles were demonstrated by TEM as well as by dynamic light scattering (mean particle size < 300 nm). In vitro studies showed a controlled dexamethasone release from hydrogels containing the drug associated to the nanocapsules following the Higuchi's squared root model (k = 20.21 +/- 2.96 mg/cm(2)/h(1/2)) compared to the hydrogels containing the free drug (k = 26.65 +/- 2.09 mg/cm(2)/h(1/2)). CONCLUSION: Taking all these results together, the hydrogel containing D-NC represent a promising approach to treat antiproliferative-related dermatological disorders.
Asunto(s)
Dexametasona/administración & dosificación , Dexametasona/química , Portadores de Fármacos/administración & dosificación , Hidrogeles/química , Hidrogeles/síntesis química , Nanocápsulas/administración & dosificación , Nanocápsulas/química , Administración Cutánea , Antiinflamatorios/administración & dosificación , Antiinflamatorios/análisis , Antiinflamatorios/química , Antiinflamatorios/farmacología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fenómenos Químicos , Dexametasona/análisis , Dexametasona/farmacología , Difusión , Portadores de Fármacos/análisis , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Composición de Medicamentos/métodos , Concentración de Iones de Hidrógeno , Inmunosupresores/administración & dosificación , Inmunosupresores/análisis , Inmunosupresores/química , Inmunosupresores/farmacología , Meristema/citología , Meristema/efectos de los fármacos , Mitosis/efectos de los fármacos , Cebollas/efectos de los fármacos , Tamaño de la Partícula , Raíces de Plantas/citología , Raíces de Plantas/efectos de los fármacos , Solubilidad , SuspensionesRESUMEN
The industrial development of polymeric nanoparticle suspensions is still limited due to their low physicochemical stability. In this paper, we evaluated the wet granulation process as an alternative method to dry polymeric nanocapsules using dexamethasone as drug model. Nanocapsule suspensions were used as granulating liquid as well as a drug-loaded-nanocarrier in the wet granulation process. Granules were evaluated regarding their drug content, mean particle size, yield, moisture content, flow properties, stability on storage, recovery studies after water redispersion and morphological characteristics (SEM). Granules containing dexamethasone-loaded polymeric nanocapsules presented good drug content (approximately 94%) and were stable for 6 months at room temperature. Morphological analyses showed nanostructures on their surface and the nanoparticles were recovered after redispersing the granules in water. These results suggest that wet granulation can be an interesting alternative to dry drug-loaded nanocapsule suspensions.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Nanocápsulas/química , Polímeros/química , Análisis de Varianza , Dexametasona/química , Estabilidad de Medicamentos , Microscopía Electrónica de Rastreo , Nanocápsulas/ultraestructura , Tamaño de la Partícula , Suspensiones/químicaRESUMEN
The influence of the polymeric amorphous materials on the physicochemical and drug release properties of drug-loaded nanocapsules as well as their role on the protection of the entrapped drug against the degradation induced by UV radiation was evaluated. Nanocapsules were prepared by interfacial deposition of preformed polymer (PLA, PLGA 50:50, and PLGA 85:15) using clobetasol propionate as the drug model. In vitro drug release was evaluated by the dialysis bag method. Photochemical stability was studied under UVA radiation. After preparation, all formulations presented nanometric mean size (180-200 nm), polydispersity index below 0.20, acid pH, negative zeta potential, and encapsulation efficiency close to 100%. Clobetasol propionate-loaded PLGA nanocapsules presented a lower physicochemical stability, showing a high drug leakage during 3 months of storage. In vitro studies showed biphasic drug release from all nanocapsules (according to an anomalous transport) and no influence of the hydrophilic characteristics of the amorphous polymeric material on the release rate. The photostability of clobetasol propionate under UVA radiation was improved by its incorporation into PLA and PLGA nanocapsules showing that besides semicrystalline polymers, amorphous polymers could also efficiently protect nanoencapsulated drugs against UV radiation.
Asunto(s)
Clobetasol/química , Cristalización/métodos , Portadores de Fármacos/química , Nanocápsulas/química , Nanocápsulas/ultraestructura , Nanomedicina/métodos , Poliésteres/química , Absorción , Clobetasol/administración & dosificación , Difusión , Portadores de Fármacos/efectos de la radiación , Estabilidad de Medicamentos , Luz , Sustancias Macromoleculares/química , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Transición de Fase , Propiedades de SuperficieRESUMEN
The aim of this study was to prepare and to evaluate the physicochemical and in vitro drug release characteristics of different nanostructured systems containing clobetasol propionate (CP): CP-loaded polymeric nanoparticles (nanocapsules and nanospheres) and CP-loaded nanoemulsion. Physicochemical characteristics of the formulations were monitored up to 9 months after preparation by means of drug content, encapsulation efficiency, mean size, polydispersity index, pH, and zeta potential. In vitro drug release studies were carried out using the dialysis bag method. Photostability of CP-loaded nanoparticles was evaluated by their exposition to UVA radiation. All formulations presented nanometric mean size (140-220 nm), polydispersity index below 0.25, neutral pH values, negative zeta potential and encapsulation efficiency close to 100%. All these parameters, except pH, remained unchangeable up to 9 months of storage at room temperature for CP-loaded nanocapsules. On the other hand, CP-loaded nanospheres and nanoemulsion showed an increase in their mean size, as well as in polydispersity index under storage (after 3 and 6 months, respectively). In vitro drug release studies showed a controlled release of CP from nanoparticles (nanocapsules > nanospheres > nanoemulsion) with a low burst release. Photostability of CP under UVA radiation was improved by its incorporation into nanoparticles (nanocapsules > nanoemulsions > nanospheres).