RESUMEN
Despite significant technological advances, rheumatoid arthritis remains an incurable disease with great impact on the life quality of patients. We studied the encapsulation of tacrolimus in lipidcore nanocapsules (TAC-LNC) as a strategy to enhance its systemic anti-arthritic properties. TAC-LNC presented unimodal distribution of particles with z-average diameter of 212 +/- 11, drug content close to the theoretical value (0.80 mg mL(-1)), and 99.43% of encapsulation efficiency. An in vitro sustained release was determined for TAC-LNC with anomalous transport mechanism (n = 0.61). In vivo studies using an arthritis model induced by Complete Freund's Adjuvant demonstrated that the animals treated with TAC-LNC presented a significantly greater inhibition of paw oedema after intraperitoneal administration. Furthermore, the encapsulation of TAC in lipid-core nanocapsules was potentially able to prevent hyperglycemia in the animals. In conclusion, TAC-LNC was prepared with 100% yield of nanoscopic particles having satisfactory characteristics for systemic use. This formulation represents a promising strategy to the treatment of rheumatoid arthritis in the near future.
Asunto(s)
Artritis Experimental/tratamiento farmacológico , Inmunosupresores , Lípidos , Nanocápsulas/química , Tacrolimus , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/metabolismo , Artritis Experimental/patología , Inmunosupresores/química , Inmunosupresores/farmacología , Lípidos/química , Lípidos/farmacología , Masculino , Tamaño de la Partícula , Ratas , Ratas Wistar , Tacrolimus/química , Tacrolimus/farmacologíaRESUMEN
Resveratrol and curcumin are two natural polyphenols extensively used due to their remarkable anti-inflammatory activity. The present work presents an inedited study of the in vivo antioedematogenic activity of these polyphenols co-encapsulated in lipid-core nanocapsules on Complete Freund's adjuvant (CFA)-induced arthritis in rats. Lipid-core nanocapsules were prepared by interfacial deposition of preformed polymer. Animals received a single subplantar injection of CFA in the right paw. Fourteen days after arthritis induction, they were treated with resveratrol, curcumin, or both in solution or loaded in lipid-core nanocapsules (1.75 mg/kg/twice daily, i.p.), for 8 days. At the doses used, the polyphenols in solution were not able to decrease paw oedema. However, nanoencapsulation improved the antioedematogenic activity of polyphenols at the same doses. In addition, the treatment with co-encapsulated polyphenols showed the most pronounced effects, where an inhibition of 37-55% was observed between day 16 and 22 after arthritis induction. This treatment minimized most of the histological changes observed, like fibrosis in synovial tissue, cartilage and bone loss. In addition, unlike conventionally arthritis treatment, resveratrol and curcumin co-encapsulated in lipid-core nanocapsules did not alter important hepatic biochemical markers (ALP, AST, and ALT). In conclusion, the strategy of co-encapsulating resveratrol and curcumin in lipid-core nanocapsules improves their efficacy as oedematogenic agents, with no evidence of hepatotoxic effects. This is a promising strategy for the development of new schemes for treatment of chronic inflammation diseases, like arthritis.
Asunto(s)
Antiinflamatorios/administración & dosificación , Artritis Experimental/tratamiento farmacológico , Curcumina/administración & dosificación , Portadores de Fármacos/administración & dosificación , Nanocápsulas/administración & dosificación , Estilbenos/administración & dosificación , Animales , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Artritis Experimental/patología , Curcumina/química , Curcumina/uso terapéutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapéutico , Articulaciones del Pie/patología , Extracto de Semillas de Uva/química , Hexosas/química , Inyecciones Intraperitoneales , Masculino , Nanocápsulas/química , Nanocápsulas/uso terapéutico , Poliésteres/química , Polisorbatos/química , Ratas Wistar , Resveratrol , Estilbenos/química , Estilbenos/uso terapéutico , Resultado del TratamientoRESUMEN
Polyphenols, which are secondary plant metabolites, gain increasing research interest due to their therapeutic potential. Among them, resveratrol and curcumin are two agents showing antioxidant, anti-inflammatory, antimicrobial as well as anticarcinogenic effects. In addition to their individual therapeutic effect, increased activity was reported upon co-delivery of the two compounds. However, due to the poor water solubility of resveratrol and curcumin, their clinical application is currently limited. In this context, lipid-core nanocapsules (LNC) composed of an oily core surrounded by a polymeric shell were introduced as drug carrier systems with the potential to overcome this obstacle. Furthermore, the encapsulation of polyphenols into LNC can increase their photostability. As the attributes of the polyphenols make them excellent candidates for skin treatment, the aim of this study was to investigate the effect of co-delivery of resveratrol and curcumin by LNC upon topical application on excised human skin. In contrast to the formulation with one polyphenol, resveratrol penetrated into deeper skin layers when the co-formulation was applied. Based on vibrational spectroscopy analysis, these effects are most likely due to interactions of curcumin and the stratum corneum, facilitating the skin absorption of the co-administered resveratrol. Furthermore, the interaction of LNC with primary human skin cells was analyzed encountering a cellular uptake within 24h potentially leading to intracellular effects of the polyphenols. Thus, the simultaneous delivery of resveratrol and curcumin by LNC provides an intelligent way for immediate and sustained polyphenol delivery for skin disease treatment.
Asunto(s)
Curcumina/administración & dosificación , Portadores de Fármacos/administración & dosificación , Nanocápsulas/administración & dosificación , Absorción Cutánea , Estilbenos/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Curcumina/química , Portadores de Fármacos/química , Liberación de Fármacos , Fibroblastos/efectos de los fármacos , Extracto de Semillas de Uva/administración & dosificación , Extracto de Semillas de Uva/química , Hexosas/administración & dosificación , Hexosas/química , Humanos , Técnicas In Vitro , Nanocápsulas/química , Aceites/administración & dosificación , Aceites/química , Poliésteres/administración & dosificación , Poliésteres/química , Polifenoles/administración & dosificación , Polifenoles/química , Resveratrol , Estilbenos/químicaRESUMEN
Olanzapine is an atypical antipsychotic drug, whose chronic use has been associated with the development of potential adverse effects such as weight gain and cardio-metabolic disorders like hypercholesterolemia and diabetes. To circumvent these side effects, the controlled release of olanzapine is a promising approach to improve adhesion of schizophrenic patients to the treatment. An innovative strategy to prolong drug release consists of loading the drug into biodegradable polymeric lipid-core nanocapsules. In this study, particle size, polydispersity, pH, zeta potential and drug loading of olanzapine-loaded lipid-core nanocapsules were analyzed. Weight gain, biochemical parameters and antipsychotic activity were evaluated in male Wistar rats. The lipid-core nanocapsules had a mean diameter of 156 +/- 13 nm, a polydispersity index lower than 0.1, a pH value of 6.12 +/- 0.14, zeta potential of -17 +/- 2.40 mV and encapsulation efficiency close to 100%. The animals treated with olanzapine-loaded lipid-core nanocapsules showed significantly lower weight gain (63.4 +/- 19.6 g) and total cholesterol levels (66.2 +/- 3.5 g x dl(-1)), compared to those administered with free olanzapine (112.6 +/- 10.3 g and 90.4 +/- 2.4 g x dl(-1)), respectively. Additionally, a more prolonged antipsychotic action was observed in the stereotyped behavior animal model induced by D,L-amphetamine, which affords to conclude that nanoencapsulation is a promising alternative to treat schizophrenic patients.