Neuroprotective effects of curcumin lipid-core nanocapsules in a model Alzheimer's disease induced by ß-amyloid 1-42 peptide in aged female mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of dementia, representing about 60-70% of cases. Curcumin is a natural compound extracted from Curcuma longa Linn, widely used in cooking, presenting several biological activities, including neuroprotection. However, it has low solubility and consequently its bioavailability is limited. In recent years, researchers have focused their attention on delivery systems based on nanotechnology because of their promising potential and advantages over conventional approaches. This study investigated the neuroprotective effects of curcumin loaded lipid-core nanocapsules (LNC) in a model of Alzheimer's disease (AD) induced by intracerebroventricular injections of ß-amyloid1-42 (Aß1-42) peptide in aged female mice, and compared these effects with those from free curcumin. Aged female mice received curcumin, free (50 mg/kg, p.o.) or loaded nanocapsules (10 or 1 mg/kg, p.o.) for 14 days after Aß1-42 administration. Aß1-42 induced significant cognitive deficit (Morris Water Maze test), as well as caused increased the levels of inflammatory cytokines in prefrontal cortex, hippocampus and serum of mice. LNC displayed significant neuroprotection against Aß1-42-induced behavioral and neurochemical changes in a model of AD. These results provide insights into the neuroprotective actions of curcumin and its nanoencapsulation as a promising approach for application as an neuroprotective agent in the prevention of AD.

Cationic and anionic unloaded polymeric nanocapsules: Toxicological evaluation in rats shows low toxicity.

The experimental design aiming at evaluating the performance of drugs nanoencapsulated involves inclusion of a formulation without drug (unloaded). This formulation has sometimes presented per se effect. In this sense, we sought to evaluate the toxicity of unloaded polymeric nanocapsules (NCs) with different surfaces (cationic and anionic) in male Wistar rats in male Wistar rats. The physicochemical characterization of NCs with different surfaces: polysorbate 80 (P80), polyethylene glycol (PEG), eudragit ®RS 100 (EUD) and chitosan (CS) was performed. Rats were treated with unloaded NCs (P80, PEG, EUD and CS surfaces) daily for 14 days per oral route. 24 h of last treatment, animals were euthanized and organs were removed and weighted. After, biochemical determinations were performed. In general, NCs-surfaces did not cause alterations in body weight, weight of organs and histopathological analysis. PEG-surface NCs did not generate hepatotoxicity. In investigation of lipid profile, the surface with P80 changed TC and HDL-C levels. Besides that, all NCs did not alter oxidative stress markers in organs studied (TBARS and Reactive Species) and CS-surface presented antioxidant activity in kidney. This study demonstrated that NCs-surfaces depending on their physicochemical characteristics had low or no toxicity.

Leishmanicidal candidate LASSBio-1736, a cysteine protease inhibitor with favorable pharmacokinetics: low clearance and good distribution.

1. LASSBio-1736 ((E)-1-4(trifluoromethyl) benzylidene)-5-(2-4-dichlorozoyl) carbonylhydrazine) is proposed to be an oral cysteine protease leishmanicidal inhibitor. 2. This work aimed to investigate plasma pharmacokinetics, protein binding and tissue distribution of LASSBio-1736 in male Wistar rats. 3. LASSBio-1736 was administered to male Wistar rats at doses of 3.2 mg/kg intravenously and 12.6 mg/kg oral and intraperitoneal. The individual plasma-concentration profiles were determined by HPLC-UV and evaluated by non-compartmental and population pharmacokinetic analysis (Monolix 2016R1, Lixoft). Tissue distribution was evaluated after iv injection of 3.2 mg/kg drug by non-compartmental approach. 4. After intravenous administration, Vdss (1.79 L/kg), t ½ (23.1 h) and CLtot (56.1 mL/h/kg) were determined, and they were statistically similar (α =0.05) to oral and intraperitoneal pharmacokinetic parameters. The plasma profiles obtained after intravenous, oral and intraperitoneal administration of the compound were best fitted to a three-compartment and one-compartment open model with first-order absorption. 5. The intraperitoneal and oral bioavailability were around 40 and 15%, respectively. 6. Liver, spleen and skin tissues showed penetration of 340, 130 and 40%, respectively, with t ½ like plasma values. 7. LASSBio-1736 protein binding was 95 ± 2%. 8. The t ½, CLtot and tissue distribution of the compound agreed with the desired drug characteristics for leishmanicidal activity.