Neurodegenerative Diseases: A Multidisciplinary Approach.

The rapid pattern of population ageing in recent years increases the risk of appearance of associated neurodegenerative diseases. Dementias are one of the most feared disorders, and although not necessarily all elderly people have dementia, the number of people with this disease is increasing rapidly. The causes of dementia are multiple, and the diagnosis of the different types of dementia is complicated since most patients display mixed dementias and symptoms overlapping. Personalized diagnosis and treatments would be desirable, but this requires a deep knowledge of each type of dementia where a multidisciplinary approach would be ideal. Thus, the aim of this review is to summarize the features of the main types of dementia as well as to compilate the more recent findings on this subject, ranging from genetic and molecular studies to animal models, including the use of omics platforms based on powerful hybrid instrumental techniques, and neuroimage techniques. On the other hand, we consider the aspects that can prevent these disorders and depend on modifiable factors, such as diet, among others. Finally, new technologies, such as nanotechnology can provide novel strategies for the administration of effective treatments. In this regard, our purpose is to provide the most updated and complete overview of state of the art about characteristics of these disorders.

Neuroprotective Natural Molecules, From Food to Brain.

The prevalence of neurodegenerative disorders is increasing; however, an effective neuroprotective treatment is still remaining. Nutrition plays an important role in neuroprotection as recently shown by epidemiological and biochemical studies which identified food components as promising therapeutic agents. Neuroprotection includes mechanisms such as activation of specific receptors, changes in enzymatic neuronal activity, and synthesis and secretion of different bioactive molecules. All these mechanisms are focused on preventing neuronal damage and alleviating the consequences of massive cell loss. Some neuropathological disorders selectively affect to particular neuronal populations, thus is important to know their neurochemical and anatomical properties in order to design effective therapies. Although the design of such treatments would be specific to neuronal groups sensible to damage, the effect would have an impact in the whole nervous system. The difficult overcoming of the blood brain barrier has hampered the development of efficient therapies for prevention or protection. This structure is a physical, enzymatic, and influx barrier that efficiently protects the brain from exogenous molecules. Therefore, the development of new strategies, like nanocarriers, that help to promote the access of neuroprotective molecules to the brain, is needed for providing more effective therapies for the disorders of the central nervous system (CNS). In order both to trace the success of these nanoplatforms on the release of the bioactive cargo in the CNS and determinate the concentration at trace levels of targets biomolecules by analytical chemistry and concretely separation instrumental techniques, constitute an essential tool. Currently, these techniques are used for the determination and identification of natural neuroprotective molecules in complex matrixes at different concentration levels. Separation techniques such as chromatography and capillary electrophoresis (CE), using optical and/or mass spectrometry (MS) detectors, provide multiples combinations for the quantitative and qualitative analysis at basal levels or higher concentrations of bioactive analytes in biological samples. Bearing this in mind, the development of food neuroprotective molecules as brain therapeutic agents is a complex task that requires the intimate collaboration and engagement of different disciplines for a successful outcome. In this sense, this work reviews the new advances achieved in the area toward a better understanding of the current state of the art and highlights promising approaches for brain neuroprotection.

Anti-tumor efficacy of chitosan-g-poly(ethylene glycol) nanocapsules containing docetaxel: anti-TMEFF-2 functionalized nanocapsules vs. non-functionalized nanocapsules.

The development and evaluation of PEGylated chitosan (CS) nanocapsules (NCs) conjugated to a monoclonal antibody anti-TMEFF-2 (CS-PEG-anti-TMEFF-2 mAb NCs) for targeted delivery of docetaxel (DCX) is presented. CS-PEG-Biotin NCs, displaying biotin tags at their surface, were obtained and efficiently functionalized with an anti-TMEFF-2 mAb through a convenient avidin-biotin approach. Cell cycle analysis after treatment with different DCX-loaded CS-PEG NC formulations indicated that the encapsulated drug remained fully active, showing a similar functional behavior to free DCX. In vivo efficacy studies using a non-small cell lung carcinoma xenograft revealed that CS-PEG-anti-TMEFF-2 NCs resulted as effective as free DCX (Taxotere®). Interestingly, differences on the pharmacodynamic behavior among the different DCX formulations were observed. Thus, while free DCX exhibited a fast and short effect on tumor volume reduction, CS-PEG-anti-TMEFF-2 mAb NCs showed a delayed and prolonged action, with no significant side effects of treatments.

Highly efficient system to deliver taxanes into tumor cells: docetaxel-loaded chitosan oligomer colloidal carriers.

Chitosan (CS) colloidal carriers, which consist of an oily core and a CS coating, were developed to facilitate a controlled intracellular delivery of docetaxel. The systems presented a particle size of <200 nm and a positive surface charge. As shown by the flow cytometry analysis, fluorescent CS carriers were rapidly internalized by human tumor cells. Fluorescence was observed in more than 80% of MCF7 (human breast adenocarcinoma) and almost 100% of A549 (human lung carcinoma) cells when a 2 h treatment with fluorescent CS carriers was given. A total of 24 h after treatment, docetaxel-loaded CS carriers had an effect on cell proliferation that was significantly greater than that of free docetaxel. These results indicate that docetaxel remains fully active upon its encapsulation into the colloidal carriers and that these systems actively transport docetaxel into cancer cells and, thus, result in a significant increase in its antiproliferative effect.