RESUMEN

Population aging is a global reality driven by increased life expectancy. This demographic phenomenon is intrinsically linked to the epidemic of cognitive disorders such as dementia and Alzheimer's disease, posing challenges for elderly and their families. In this context, the search for new therapeutic strategies to prevent or minimize cognitive impairments becomes urgent, as these deficits are primarily associated with oxidative damage and increased neuroinflammation. Ferulic acid (FA), a natural and potent antioxidant compound, is proposed to be nanoencapsulated to target the central nervous system effectively with lower doses and an extended duration of action. Here, we evaluated the effects of the nanoencapsulated FA on d-galactose (d-Gal)- induced memory impairments. Male Wistar adult rats were treated with ferulic acid-loaded nanocapsules (FA-Nc) or non-encapsulated ferulic acid (D-FA) for 8 weeks concurrently with d-Gal (150 mg/kg s.c.) injection. As expected, our findings showed that d-Gal injection impaired memory processes and increased anxiety behavior, whereas FA-Nc treatment ameliorated these behavioral impairments associated with the aging process induced by d-Gal. At the molecular level, nanoencapsulated ferulic acid (FA-Nc) ameliorated the decrease in ACh and glutamate induced by d-galactose (d-Gal), and also increased GABA levels in the dorsal hippocampus, indicating its therapeutic superiority. Additional studies are needed to elucidate the mechanisms underlying our current promising outcomes. Nanoscience applied to pharmacology can reduce drug dosage, thereby minimizing adverse effects while enhancing therapeutic response, particularly in neurodegenerative diseases associated with aging. Therefore, the strategy of brain-targeted drug delivery through nanoencapsulation can be effective in mitigating aging-related factors that may lead to cognitive deficits.

RESUMEN

This work investigated the impact of formulation including in vitro release profile, repeated dosing, and nail poration on the ex vivo nail delivery performance of antifungal formulations. Chitosan coated and uncoated tioconazole-loaded nanocapsules and a nano-based film-forming vehicle were assessed via in vitro release and in vitro permeation tests using an artificial membrane and human nail clippings, respectively. The later involved single and daily dosing experiments with intact and porated nails. Additional experiments with Nile Red-loaded formulations evaluated the depth of penetration of the fluorescent marker into the nail by laser scanning confocal microscopy. The nanocapsule formulations prolonged release of tioconazole for longer than the control solutions and this ability was related to an enhanced nail penetration of the drug. Further, the new film-forming formulation delivered its drug payload more efficiently than a marketed product. Daily dosing of the formulations doubled the amount of drug recovered from the nails. Porating the nails enhanced tioconazole delivery in single dose experiments only. The depth of penetration of Nile Red into the nails clippings ranged between 90-160 µm. This research suggests that ensuring prolonged release of a drug is fundamental to develop efficacious topical nail formulations.

Asunto(s)

RESUMEN

Dithranol is a very effective drug for the topical treatment of psoriasis. However, it has some adverse effects such as irritation and stain in the skin that make its application and patient adherence to treatment difficult. The aims of this work were to prepare and characterize dithranol-loaded nanocapsules as well as to evaluate the photostability and the irritation potential of these nanocarriers. Lipid-core nanocapsules containing dithranol (0.5 mg/mL) were prepared by interfacial deposition of preformed polymer. EDTA (0.05%) or ascorbic acid (0.02%) was used as antioxidants. After preparation, dithranol-loaded lipid-core nanocapsules showed satisfactory characteristics: drug content close to the theoretical concentration, encapsulation efficiency of about 100%, nanometric mean size (230-250 nm), polydispersity index below 0.25, negative zeta potential, and pH values from 4.3 to 5.6. In the photodegradation study against UVA light, we observed a higher stability of the dithranol-loaded lipid-core nanocapsules comparing to the solution containing the free drug (half-life times around 4 and 1h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing EDTA, respectively; half-life times around 17 and 7h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing ascorbic acid, respectively). Irritation test by HET-CAM method was conducted to evaluate the safety of the formulations. From the results it was found that the nanoencapsulation of the drug decreased its toxicity compared to the effects observed for the free drug.

Asunto(s)