Anti-amyloidogenic amphipathic arginine-dehydrophenylalanine spheres capped selenium nanoparticles as potent therapeutic moieties for Alzheimer's disease.

Aggregation of both amyloid beta (Aß) peptide and hyperphosphorylated tau proteins is the major pathological hallmark of Alzheimer's disease (AD). Moieties that carry anti-amyloidogenic potency against both of the aggregating entities are considered to be promising drug candidatures for the disease. In the current work, we have synthesized amphipathic dipeptide vesicle-templated selenium nanoparticles (RΔF-SeNPs) as potential entities to combat AD. We have investigated and established their anti-amyloidogenic activity against different peptide-based amyloid models, such as the reductionist model based on the dipeptide phenylalanine-phenylalanine (FF) derived from Aß; a model based on the hexapeptide Ac-PHF6 (306VQIVYK311) derived from tau protein; and the full-length Aß42 polypeptide-based model. We also evaluated the neuroprotective characteristics of RΔF-SeNPs against FF, Ac-PHF6, and Aß42 fibril-induced toxicity in neuroblastoma, SH-SY5Y cells. RΔF-SeNPs further exhibited neuroprotective effects in streptozotocin (STZ) treated neuronal (N2a) cells carrying AD-like features. In addition, studies conducted in an intra-cerebroventricular STZ-instigated rat model of dementia revealed that RΔF-SeNP-treated animals showed improved cognitive activity and reduced Aß42 aggregate burden in brain tissues as compared with the STZ-treated group. Moreover, in vivo brain distribution studies conducted in animal models additionally demonstrated the brain-homing ability of RΔF-SeNPs. All together, these studies supported the potency of RΔF-SeNPs as efficient and propitious disease-modifying therapeutic agents for combating AD.

Preparation and evaluation of dermal delivery system of griseofulvin containing vitamin E-TPGS as penetration enhancer.

Griseofulvin, an antifungal agent, is a BCS class II drug slowly, erratically, and incompletely absorbed from the gastrointestinal tract in humans. The clinical failure of the conventional oral therapy of griseofulvin is most likely attributed to its poor solubility and appreciable inter- and intra-subject variation in bioavailability from different commercial products. Moreover, the conventional oral therapy is associated with numerous adverse effects and interactions with other drugs. The purpose of the study was to formulate a topical application of griseofulvin which would deliver the drug locally in a therapeutically effective concentration. Griseofulvin was solubilized in ethanol, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and combinations of ethanol with varying amounts of TPGS; then, it was incorporated in the Carbopol (980 NF) base. The formulations were characterized and evaluated ex vivo using Laca mice skin, microbiologically against Microsporum gypseum and Microsporum canis and clinically in a small group of patients. The current study suggested that TPGS and ethanol synergistically enhanced the drug permeation and drug retention in the skin. The selected formulation F VII was found to be effective against M. gypseum and M. canis, non-sensitizing, histopathologically safe, stable at 4°C, 25°C, and 40°C with respect to percent drug content, permeation characteristics, pH, transparency, feel, viscosity, and clinically effective in a small group of subjects. The proposed topical formulation of griseofulvin may be an effective and convenient alternative to the currently available oral therapy for the treatment of superficial fungal infections.