RESUMEN
Capsaicin (CAP) is a secondary metabolite with high therapeutic potential. It displays several bioactive properties including hypolipidemic, antioxidant, anti-inflammatory and analgesic effects. However, CAP presents toxicity to healthy cells and poor pharmacokinetic profile, which is characterized by toxic metabolites and short half-life. In this study, CAP-loaded albumin nanoparticles were obtained by the desolvation-coacervation method. The preparation process was optimized by the application of a factorial design. Nanoparticles presented diameter of about 200â¯nm, quasi-spherical morphology, encapsulation efficiency of 98.3⯱â¯7.4%, and negative zeta potential. The in vitro release assay demonstrated a biphasic profile, characterized by a fast release over 12â¯h followed by a prolonged release rate. Nanoencapsulated CAP showed significant antioxidant activity in an in vitro assay which was concentration - and time-dependent. In addition, the in vivo study demonstrated for the first time that both free and nanoencapsulated drug reduced TNF-alpha concentrations in the absence of inflammatory stimuli model. These novel findings indicate that albumin nanoparticles are potential CAP carriers and that this new drug formulation may be useful in several conditions, including cancer, inflammation, and neuropathic pain.
Asunto(s)
Capsaicina , Nanocápsulas , Albúmina Sérica Bovina , Animales , Capsaicina/química , Capsaicina/farmacocinética , Capsaicina/farmacología , Bovinos , Masculino , Nanocápsulas/química , Nanocápsulas/uso terapéutico , Ratas , Ratas Wistar , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/farmacocinética , Albúmina Sérica Bovina/farmacologíaRESUMEN
Pneumocystis carinii is typically a non-pathogenic fungus found in the respiratory tract of healthy humans. However, it may cause P. carinii pneumonia (PCP) in people with immune deficiency, affecting mainly premature babies, cancer patients and transplant recipients, and people with acquired immunodeficiency syndrome (AIDS). In the latter group, PCP occurs in approximately 80% of patients, a major cause of death. Currently, there are many available therapies to treat PCP patients, including P. carinii dihydrofolate reductase (PcDHFR) inhibitors, such as trimetrexate (TMX), piritrexim (PTX), trimethoprim (TMP), and pyrimethamine (PMT). Nevertheless, the high percentage of adverse side effects and the limited therapeutic success of the current drug therapy justify the search for new drugs rationally planned against PCP. This work focuses on the study of pyrimidine inhibitors of PcDHFR, using both CoMFA and CoMSIA 3D-QSAR methods.
Asunto(s)
Antagonistas del Ácido Fólico/química , Antagonistas del Ácido Fólico/farmacología , Pneumocystis carinii/enzimología , Pirimidinas/química , Pirimidinas/farmacología , Relación Estructura-Actividad Cuantitativa , Tetrahidrofolato Deshidrogenasa/metabolismo , Dominio Catalítico , Humanos , Concentración 50 Inhibidora , Modelos Moleculares , Electricidad EstáticaRESUMEN
This paper describes CoMFA and CoMSIA studies for affinity and selectivity of a series of indole ligands to cannabinoid CB1 and CB2 receptors. The developed models have proven to be predictive, with average q(2) of 0.675 and average r(2) of 0.855, demonstrating a good statistical validation. The obtained results have helped us to understand the structural motifs that are responsible for the affinity and selectivity of some of these derivatives towards each subtype of cannabinoid receptor and have demonstrated that the exploited 3D-QSAR methods could be useful tools for the design of new safer analogues presenting better affinity and selectivity profiles.