RESUMO
Understanding the central nervous system (CNS) circuitry and its different neurotransmitters that underlie reward is essential to improve treatment for many common health issues, such as addiction. Here, we concentrate on understanding how the mesolimbic circuitry and neurotransmitters are organized and function, and how drug exposure affects synaptic and structural changes in this circuitry. While the role of some reward circuits, like the cerebral dopamine (DA)/glutamate (Glu)/gamma aminobutyric acid (GABA)ergic pathways, in drug reward, is well known, new research using molecular-based methods has shown functional alterations throughout the reward circuitry that contribute to various aspects of addiction, including craving and relapse. A new understanding of the fundamental connections between brain regions as well as the molecular alterations within these particular microcircuits, such as neurotrophic factor and molecular signaling or distinct receptor function, that underlie synaptic and structural plasticity evoked by drugs of abuse has been made possible by the ability to observe and manipulate neuronal activity within specific cell types and circuits. It is exciting that these discoveries from preclinical animal research are now being applied in the clinic, where therapies for human drug dependence, such as deep brain stimulation and transcranial magnetic stimulation, are being tested. Therefore, this chapter seeks to summarize the current understanding of the important brain regions (especially, mesolimbic circuitry) and neurotransmitters implicated in drug-related behaviors and the molecular mechanisms that contribute to altered connectivity between these areas, with the postulation that increased knowledge of the plasticity within the drug reward circuit will lead to new and improved treatments for addiction.
RESUMO
New formulations of Amphotericin-B (Am-B), the most popular therapeutic drug for many human infections such as parasitic and fungal pathogens, are safe, economical, and effective in the world. Several newly designed carrier systems for Am-B can also be considered orally with sufficient gastrointestinal permeability and good solubility. However, the clinical application of several new formulations of Am-B with organ cytotoxicity, low bioavailability, high costs, and technical problems have caused some issues. Therefore, more attention and scientific design are required to progress safe and effective drug delivery systems. Currently, the application of nano-based technology and nanomaterials in the advancement of drug delivery systems exhibits promising outcomes to cure many human systemic infections. Designing novel drug delivery systems including solid lipid nanostructured materials, lipo-polymersomes, drug conjugates and microneedles, liposomes, polymer and protein-based nanostructured materials, dendrimers, emulsions, mixed micelles, polymeric micelles, cyclodextrins, nanocapsules, and nanocochleate for Am-B has many advantages to reducing several related issues. The unique properties of nanostructured particles such as proper morphology, small size, surface coatings, and, electrical charge, permit scientists to design new nanocomposite materials against microorganisms for application in various human diseases. These features have made these nanoparticles an ideal candidate for drug delivery systems in clinical approaches to cure a number of human disorders and currently, several therapeutic nanostructured material formulations are under different stages of clinical tests. Hence, this scientific paper mainly discussed the advances in new formulations of Am-B for the treatment of human systemic infections and related clinical tests.