The pharmacological properties of many drugs can be improved by drug delivery systems able to drive therapeutic agents to target regions. The use of carriers, in fact, may reduce possible cytotoxic effects of drugs and increase their bioavailability at the site of action, thus improving the efficacy and the safety of treatments. Therefore, we have developed an erythrocyte-based drug delivery system (erythro-magneto-HA virosome), which has the potential to be magnetically guided to specific sites and to fuse with target cells. These engineered erythrocytes have demonstrated in previous work a very high in vitro capability to release anticancer drugs directly inside target cells. Because the erythro-magneto-HA virosomes (EMHVs) proved to be promising carriers, we decided to investigate in more details the effectiveness and safety of this erythrocyte-based drug delivery system.

We evaluated the ability of the EMHVs to be specifically localized in vivo to desired sites by means of an external magnetic field and to protect an anticancer drug such as 5-Aza-2’-deoxycytidine from degradation. Additionally we have assessed the ability of the EMHVs to act as bioreactors and to convert the pro-drug 5-Aza-2’-deoxycytidine into an active drug. Finally, we have studied the interaction of the EMHVs with the host immune system.

The pro-drug 5-Aza-2’-deoxycytidine has short half-life when systemically injected and needs to be phosphorylated to become an active drug. We found that when inside the engineered erythrocytes it is protected by degradation and is transformed in its active form thus becoming readily available for uptake by the targeted cells. Moreover, we have observed that the EMHVs used didn’t cause either a cell-mediated or a humoral immune response in host mice having the same haplotype of the donors.

These findings suggest that erythro-magneto-HA virosomes are a safe and useful drug delivery system that may offer numerous advantages for several clinical applications.

Human α-Lactalbumin Made Lethal to Tumors (HAMLET) or its bovine counterpart BAMLET is an α-Lactalbumin (α-LA)-oleic acid (OA) complex which induces death to tumor cells, selectively. Although HAMLET or its bovine counterpart BAMLET is prepared chromatographically, it has also been reported that HAMLET or BAMLET-like complexes can be formed by direct mixing of the two components. In this study, we prepare BAMLET-like complexes with reference to the literature, characterize and benchmark these with respect to cytotoxicity, ability to disrupt the integrity of artificial membranes, as well as spectroscopic and physicochemical properties. We show that mixing bovine α-Lactalbumin (BLA) with pure OA (liquid form), followed by incubation and shaking at 37°C is the most attractive choice for preparing BLA-OA complexes (resulting complex referred to as BLAOA (pure)). Pre-dissolving OA in methanol or ethanol and then mixing with BLA also produces a complex (referred to as BLAOA (methanol) or BLAOA (ethanol)) with similar activities as BAMLET. BLA mixed with OA pre-dispersed in phosphate buffer forms little of the active complex.

This study aimed to evaluate the oral acute and sub chronic toxicity of Quassia amara (Q. amara) extract.
For the acute toxicity study, six male and six female rats received 2000 and 5000 mg/kg Q. amara extract. Rats were observed for 14 days; after sacrifice, liver, kidneys, lung, spleen and heart were submitted to macroscopic analysis. No death occurred and just the liver presented significant difference compared to the control group. For subchronic toxicity, eight groups of 6 male and 6 female rats received 200, 400 and 800 μg/mL of extract of Q. amara. Prothrombin time, bilirubin, urea, creatinine and gamma glutamyl transpeptidase (γ-GT), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were used as markers of renal and hepatobiliary function, respectively. The male showed a slight rise in serum bilirubin and creatinine and the female slight rise of AST, ALT and ALP activities. The urinalyses (pH, density, glucose and leukocytes) showed no change relative to the control. The NOAEL of 35 mg/kg and RfD 0.35 mg/kg/day encourage us to isolate the active principles in order to discover which molecules of this extract showed better antimycobacterial activity.

The multiple lines of evidence demonstrate that melatonin exerts powerful antioxidant actions by preventing and
scavenging free radicals in a direct and indirect manner. Importantly, melatonin reduced post-ischemic oxidative/
nitrosative damage to the afflicted neurovascular units and improved the preservation of blood-brain barrier
permeability in various brain diseases. The information compiled here will serve as a comprehensive reference
for the neurovascular protective actions of melatonin to date, and will hopefully help to design further experimental research and expand melatonin as neurovascular protective agent in neurovascular diseases.

A fast, efficient and green microwave-assisted synthesis of ultra-small, superparamagnetic iron oxide nanoparticles is reported. By controlling the temperature and heating mode of a polyol reduction using triethylene glycol (TREG) as a green, high-boiling solvent, ultra-small nanoparticles (2-4 nm) exhibiting robust superparamagnetic behavior were obtained. The sizes of the nanoparticles were determined by TEM and DLS measurements. Using a ligand exchange process, the TREG molecules on the surface of the smallest nanoparticles (2 nm) were successfully replaced with Alendronate, an anti-cancer drug molecule, effectively transforming the nanoparticles into a potential theranostic agent.