Neuroprotective-Neurorestorative Effects Induced by Progesterone on Global Cerebral Ischemia: A Narrative Review.

Progesterone (P4) is a neuroactive hormone having pleiotropic effects, supporting its pharmacological potential to treat global (cardiac-arrest-related) cerebral ischemia, a condition associated with an elevated risk of dementia. This review examines the current biochemical, morphological, and functional evidence showing the neuroprotective/neurorestorative effects of P4 against global cerebral ischemia (GCI). Experimental findings show that P4 may counteract pathophysiological mechanisms and/or regulate endogenous mechanisms of plasticity induced by GCI. According to this, P4 treatment consistently improves the performance of cognitive functions, such as learning and memory, impaired by GCI. This functional recovery is related to the significant morphological preservation of brain structures vulnerable to ischemia when the hormone is administered before and/or after a moderate ischemic episode; and with long-term adaptive plastic restoration processes of altered brain morphology when treatment is given after an episode of severe ischemia. The insights presented here may be a guide for future basic research, including the study of P4 administration schemes that focus on promoting its post-ischemia neurorestorative effect. Furthermore, considering that functional recovery is a desired endpoint of pharmacological strategies in the clinic, they could support the study of P4 treatment for decreasing dementia in patients who have suffered an episode of GCI.

Targeted delivery of temozolomide by nanocarriers based on folic acid-hollow TiO2 -nanospheres for the treatment of glioblastoma.

Glioblastoma multiforme (GBM) is a highly malignant brain tumor. Its standard treatment includes a combination of surgery, radiation, and chemotherapy. The last involves the oral delivery of free drug molecules to GBM such as Temozolomide (TMZ). However, this treatment has limited effectiveness owing to the drugs premature degradation, lack of cell selectivity, and poor control of pharmacokinetics. In this work, the development of a nanocarrier based on hollow titanium dioxide (HT) nanospheres functionalized with folic acid (HT-FA) for the targeted delivery of temozolomide (HT-TMZ-FA) is reported. This approach has the potential benefits of prolonging TMZ degradation, targeting GBM cells, and increasing TMZ circulation time. The HT surface properties were studied, and the nanocarrier surface was functionalized with folic acid as a potential targeting agent against GBM. The loading capacity, protection from degradation, and drug retention time were investigated. Cell viability was performed to assess the cytotoxicity of HT against LN18, U87, U251, and M059K GBM cell lines. The cell internalization of HT configurations (HT, HT-FA, HT-TMZ-FA) was evaluated to study targeting capabilities against GBM cancer. Results show that HT nanocarriers have a high loading capacity, retain and protect TMZ for at least 48 h. Folic acid-functionalized HT nanocarriers successfully delivered and internalized TMZ to glioblastoma cancer cells with high cytotoxicity through autophagic and apoptotic cellular mechanisms. Thus, HT-FA nanocarriers could be a promising targeted delivery platform for chemotherapeutic drugs for the treatment of GBM cancer.

Synthesis and characterization of V2O5-Ga2O3 photocatalysts and their application on the photocatalytic reduction of CO2.

The photocatalytic reduction of carbon dioxide (CO2) to produce methanol (CH3OH) is a promising strategy for producing clean energy. The catalyst, the aqueous medium, and the UV light are key parameters for the formation of the most relevant pair (e-/h+) and the specific selectivity towards the desired product (methanol). The use of Ga2O3 and V2O5 in the photocatalytic reduction of CO2 to produce methanol has been little studied. However, the combination of these oxides is important to generate synergies and decrease the band energy, enhancing the photocatalytic activity in CO2 reduction. In this work, V2O5-Ga2O3 combined photocatalysts have been prepared and investigated for the photocatalytic reduction of CO2. These photocatalysts were characterized by spectroscopic and microscopic techniques. The results showed that textural properties such as surface area and morphology do not influence the photocatalytic activity. However, species such as Ga2p3/2 and Ga2p1/2 identified by XPS enhanced the photocatalytic activity, most likely due to the formation of vacancies and the reduction of the bandgap in the combined oxides, as compared to single oxides. The contribution of these factors in pair interactions (e-/h+) with CO2 to generate methanol is demonstrated.

Amyloid ß, Lipid Metabolism, Basal Cholinergic System, and Therapeutics in Alzheimer's Disease.

The presence of insoluble aggregates of amyloid ß (Aß) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aß peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each presenting different levels of toxicity. Aß peptides can be internalized by particular receptors and trigger changes from Tau phosphorylation to alterations in cognitive function, through dysfunction of the cholinergic system. The goal of this review is to summarize the current knowledge on the role of lipids in Alzheimer's disease and their relationship with the basal cholinergic system, as well as potential disease-modifying therapies.

Lactate-Loaded Nanoparticles Induce Glioma Cytotoxicity and Increase the Survival of Rats Bearing Malignant Glioma Brain Tumor.

A glioblastoma is an aggressive form of a malignant glial-derived tumor with a poor prognosis despite multimodal therapy approaches. Lactate has a preponderant role in the tumor microenvironment, playing an immunoregulatory role as well as being a carbon source for tumor growth. Lactate homeostasis depends on the proper functioning of intracellular lactate regulation systems, such as transporters and enzymes involved in its synthesis and degradation, with evidence that an intracellular lactate overload generates metabolic stress on tumor cells and tumor cell death. We propose that the delivery of a lactate overload carried in nanoparticles, allowing the intracellular release of lactate, would compromise the survival of tumor cells. We synthesized and characterized silica and titania nanoparticles loaded with lactate to evaluate the cellular uptake, metabolic activity, pH modification, and cytotoxicity on C6 cells under normoxia and chemical hypoxia, and, finally, determined the survival of an orthotopic malignant glioma model after in situ administration. A dose-dependent reduction in metabolic activity of treated cells under normoxia was found, but not under hypoxia, independent of glucose concentration. Lactated-loaded silica nanoparticles were highly cytotoxic (58.1% of dead cells) and generated significant supernatant acidification. In vivo, lactate-loaded silica nanoparticles significantly increased the median survival time of malignant glioma-bearing rats (p = 0.005) when administered in situ. These findings indicate that lactate-loaded silica nanoparticles are cytotoxic on glioma cells in vitro and in vivo.

Cytotoxic Activity of Cu/TiO2 Nanoparticles on Uterine-Cervical Cancer Cells.

Nanoparticles based on metal oxides serve as carrier matrices for molecules of biological interest. In this work, we used different copper complexes that were coupled to TiO2 nanoparticles. Nanoparticles were prepared with the sol-gel method. The Cu/TiO2 nanoparticles were characterized through ultraviolet-visible and Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, nitrogen physisorption analysis, and scanning electron microscopy. Their biological activity was determined through DNA degradation and their cytotoxic effect on HeLa cells. The Cu/TiO2 nanoparticles presented a pore size between 2 and 6 nm, the size of nanoparticles agglomerates was between 100 and 500 nm. The nanoparticles of Cu/TiO2 degraded DNA starting at 15 min. The half maximal inhibitory concentration in HeLa cells depends on the used cooper complexes, the kinetics of cell death is of first order. Results revealed that these nanoparticles could be applied in uterine-cervical cancer treatment.

Preparation and characterisation of silica-based nanoparticles for cisplatin release on cancer brain cells.

In the present work, the preparation, characterisation, and efficiency of two different silica nanostructures as release vehicles of Cisplatin are reported. The 1-hexadeciltrimethyl-ammonium bromide templating agent was used to obtain mesoporous silica nanoparticles which were later loaded with Cisplatin. While sol-gel silica was very fast prepared using an excess of acetic acid during the hydrolysis-condensation reactions of tetraethylorthosilicate and at the same time the Cisplatin was added. Several physicochemical techniques including spectroscopies, electronic microscopy, X-ray diffraction, N2 adsorption-desorption were used to characterise the silica nanostructures. An in vitro Cisplatin release test was carried out using artificial cerebrospinal fluid. Finally, the toxicity of all silica nanostructures was tested using the C6 cancer cell line. The spectroscopic results showed the suitable stabilisation of Cisplatin into the two different silica nanostructures. A large surface area was obtained for the mesoporous silica nanoparticles, while low areas were obtained in the silica nanoparticles. Cisplatin was released faster from mesoporous silica channels than from inside of aggregates nanoparticles silica. Cisplatin alone, as well as, cisplatin released from both silica nanostructures exerted a toxic effect on cancer cells. In contrast, both silica structures without the drug did not exert any toxic effect.

Nanobiomaterials' applications in neurodegenerative diseases.

The blood-brain barrier is the interface between the blood and brain, impeding the passage of most circulating cells and molecules, protecting the latter from foreign substances, and maintaining central nervous system homeostasis. However, its restrictive nature constitutes an obstacle, preventing therapeutic drugs from entering the brain. Usually, a large systemic dose is required to achieve pharmacological therapeutic levels in the brain, leading to adverse effects in the body. As a consequence, various strategies are being developed to enhance the amount and concentration of therapeutic compounds in the brain. One such tool is nanotechnology, in which nanostructures that are 1-100 nm are designed to deliver drugs to the brain. In this review, we examine many nanotechnology-based approaches to the treatment of neurodegenerative diseases. The review begins with a brief history of nanotechnology, followed by a discussion of its definition, the properties of most reported nanomaterials, their biocompatibility, the mechanisms of cell-material interactions, and the current status of nanotechnology in treating Alzheimer's, Parkinson's diseases, and amyotrophic lateral sclerosis. Of all strategies to deliver drug to the brain that are used in nanotechnology, drug release systems are the most frequently reported.

Catalytic nanomedicine technology: copper complexes loaded on titania nanomaterials as cytotoxic agents of cancer cell.

The anticancer properties of pure copper (II) acetate and copper (II) acetylacetonate, alone and loaded on functionalized sol-gel titania (TiO(2)), were determined in four different cancer cell lines (C6, RG2, B16, and U373), using increasing concentrations of these compounds. The copper complexes were loaded onto the TiO(2) network during its preparation by the solgel process. Once copper-TiO(2) materials were obtained, these were characterized by several physical-chemical techniques. An in vitro copper complex-release test was developed in an aqueous medium at room temperature and monitored by ultraviolet spectroscopy. The toxic effect of the copper complexes, alone and loaded on TiO(2), was determined using a cell viability 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, when cancer cells were treated with increasing concentrations (15.75-1000 mg/mL) of these. Characterization studies revealed that the addition of copper complexes to the TiO(2) sol-gel network during its preparation, did not generate changes in the molecular structure of the complexes. The surface area, pore volume, and pore diameter were affected by the copper complex additions and by the crystalline phases obtained. The kinetic profiles of both copper complexes released indicated two different stages of release: The first one was governed by first-order kinetics and the second was governed by zero-order kinetics. The cell viability assay revealed a cytotoxic effect of copper complexes, copper-TiO(2), and cisplatin in a dose-dependent response for all the cell lines; however, the copper complexes exhibited a better cytotoxic effect than the cisplatin compound. TiO(2) alone presented a minor cytotoxicity for C6 and B16 cells; however, it did not cause any toxic effect on the RG2 and U373 cells, which indicates its high biocompatibility with these cells.

Treatment of Parkinson's disease: nanostructured sol-gel silica-dopamine reservoirs for controlled drug release in the central nervous system.

INTRODUCTION: We have evaluated the use of silica-dopamine reservoirs synthesized by the sol-gel approach with the aim of using them in the treatment of Parkinson's disease, specifically as a device for the controlled release of dopamine in the striatum. Theoretical calculations illustrate that dopamine is expected to assume a planar structure and exhibit weak interactions with the silica surface. METHODS: Several samples were prepared by varying the wt% of dopamine added during the hydrolysis of tetraethyl orthosilicate. The silica-dopamine reservoirs were characterized by N(2) adsorption, scanning and transmission electron microscopy, and Fourier transform infrared spectroscopy. The in vitro release profiles were determined using ultraviolet visible absorbance spectroscopy. The textural analyses showed a maximum value for the surface area of 620 m(2)/g nanostructured silica materials. The stability of dopamine in the silica network was confirmed by infrared and (13)C-nuclear magnetic resonance spectroscopy. The reservoirs were evaluated by means of apomorphine-induced rotation behavior in hemiparkisonian rats. RESULTS: The in vitro dopamine delivery profiles indicate two regimes of release, a fast and sustained dopamine delivery was observed up to 24 hours, and after this time the rate of delivery became constant. Histologic analysis of formalin-fixed brains performed 24-32 weeks after reservoir implantation revealed that silica-dopamine implants had a reddish-brown color, suggesting the presence of oxidized dopamine, likely caused by the fixation procedure, while implants without dopamine were always translucent. CONCLUSION: The major finding of the study was that intrastriatal silica-dopamine implants reversed the rotational asymmetry induced by apomorphine, a dopamine agonist, in hemiparkinsonian rats. No dyskinesias or other motor abnormalities were observed in animals implanted with silica or silica-dopamine.

Room temperature olefins oligomerization over sulfated titania.

Oligomerization reaction was carried out at room temperature using sulfated titania as catalyst. Total isobutene conversion was obtained with high stability for a long period of time. In case of deactivation, total reactivation of the catalyst was reached.