Secondary Metabolites with Antioxidant Activities for the Putative Treatment of Amyotrophic Lateral Sclerosis (ALS): "Experimental Evidences".

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that is characterized by progressive loss of the upper and lower motor neurons at the spinal or bulbar level. Oxidative stress (OS) associated with mitochondrial dysfunction and the deterioration of the electron transport chain are factors that contribute to neurodegeneration and perform a potential role in the pathogenesis of ALS. Natural antioxidant molecules have been proposed as an alternative form of treatment for the prevention of age-related neurological diseases, in which ALS is included. Researches support that regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in this disease, and antioxidant drugs are aimed at a promising pathway to treatment. Among the strategies used for obtaining new drugs, we can highlight the isolation of secondary metabolite compounds from natural sources that, along with semisynthetic derivatives, correspond to approximately 40% of the drugs found on the market. Among these compounds, we emphasize oxygenated and nitrogenous compounds, such as flavonoids, coumarins, and alkaloids, in addition to the fatty acids, that already stand out in the literature for their antioxidant properties, consisting in a part of the diets of millions of people worldwide. Therefore, this review is aimed at presenting and summarizing the main articles published within the last years, which represent the therapeutic potential of antioxidant compounds of natural origin for the treatment of ALS.

Bemotrizinol-Loaded Carnauba Wax-Based Nanostructured Lipid Carriers for Sunscreen: Optimization, Characterization, and In vitro Evaluation.

Nanostructured lipid carriers (NLC) are aqueous dispersions of nanoparticles formed by solid and liquid lipids. In this study, NLC containing an organic UV filter, bemotrizinol, were developed for sunscreen formulation using carnauba wax and caprylic/capric triglycerides through ultrasonication technique. A Box-Behnken design was used to evaluate the influence of three variables on the particle size with the purpose of choosing the best system for further characterization. The particle size decreased as the surfactant concentration increased, reaching an average size of 122.4 ± 0.3 nm at 30 days of storage. Scanning electron microscopy showed intact and spherical particles. Thermal analysis and Fourier-transform infrared spectroscopy suggest that bemotrizinol was incorporated into the NLC. The X-ray diffraction showed a reduction in the crystallinity of the NLC. In vitro analysis indicated an improvement in the photoprotective activity of bemotrizinol when incorporated into NLC. These findings suggest a promising, stable, and biocompatible system.

Advances in the use of MOFs for Cancer Diagnosis and Treatment: An Overview.

Nanoparticles as drug delivery systems and diagnostic agents have gained much attention in recent years, especially for cancer treatment. Nanocarriers improve the therapeutic efficiency and bioavailability of antitumor drugs, besides providing preferential accumulation at the target site. Among different types of nanocarriers for drug delivery assays, metal-organic frameworks (MOFs) have attracted increasing interest in the academic community. MOFs are an emerging class of coordination polymers constructed of metal nodes or clusters and organic linkers that show the capacity to combine a porous structure with high drug loading through distinct kinds of interactions, overcoming the limitations of traditional drug carriers explored up to date. Despite the rational design and synthesis of MOFs, structural aspects and some applications of these materials like gas adsorption have already been comprehensively described in recent years; it is time to demonstrate their potential applications in biomedicine. In this context, MOFs can be used as drug delivery systems and theranostic platforms due to their ability to release drugs and accommodate imaging agents. This review describes the intrinsic characteristics of nanocarriers used in cancer therapy and highlights the latest advances in MOFs as anticancer drug delivery systems and diagnostic agents.

Physicochemical Characterization of Bioactive Compounds in Nanocarriers.

The encapsulation of bioactive compounds is an emerging technique for finding new medicines since it provides protection against ambient degradation factors before reaching the target site. Nanotechnology provides new methods for encapsulating bioactive compounds and for drug carrier development. Nanocarriers satisfactorily impact the absorption, distribution, metabolism, and excretion rate when compared to conventional carriers. The nanocarrier material needs to be compatible and bind to the drug and be bio-resorbable. In this context, the physicochemical characterization of encapsulated bioactive compounds is fundamental to guarantee the quality, reproducibility, and safety of the final pharmaceutical product. In this review, we present the physicochemical techniques most used today by researchers to characterize bioactive compounds in nanocarriers and the main information provided by each technique, such as morphology, size, degree of crystallinity, long-term stability, the efficacy of drug encapsulation, and the amount released as a function of time.

Therapeutic Potential of Melaleuca alternifolia Essential Oil in New Drug Delivery Systems.

Medicinal plants produce secondary metabolites with special biological activities, which may be used as new therapeutic alternatives. For instance, tea tree essential oil (TTO) was shown to exert antimicrobial, antifungal, anthelmintic, antiviral, anti-tumor and anti-inflammatory activities. Due to their thermal instability, active principles can be easily degraded by physicochemical processes; therefore, they must be protected to increase their time of action and improve their controlled release. The aim of this review is to discuss formulations incorporating encapsulated TTO as the active ingredient. Micro and nanoencapsulated systems proved to be more thermostable than TTO and to exert better antimicrobial, antifungal, antiparasitic and larvicidal effects. Nanoencapsulation also reduced oil toxicity. Emulsified and hybrid systems developed by various methods showed improved repellent, antibacterial, antifungal and anti-inflammatory activities, thereby proving promising for the pharmaceutical industry. Liposomal formulations produced by hydration of lipid films exhibited constant rate of terpinen-4-ol release. In addition, their incorporation into biomaterials, such as sponges, nanofibers and films, showed great potential for treating infections. Mainly due to the advantages of their incorporation into new drug delivery systems over conventional formulations, there is an interest in the development of systems containing TTO as a pharmaceutical ingredient of plant origin.

Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy.

Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ±â€¯0.58% and 27.7 ±â€¯3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 µM of PS present non-toxic with >80 ±â€¯6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ±â€¯4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer.

Stimuli-responsive Drug Delivery Nanocarriers in the Treatment of Breast Cancer.

Stimuli-responsive drug-delivery nanocarriers (DDNs) have been increasingly reported in the literature as an alternative for breast cancer therapy. Stimuli-responsive DDNs are developed with materials that present a drastic change in response to intrinsic/chemical stimuli (pH, redox and enzyme) and extrinsic/physical stimuli (ultrasound, Near-infrared (NIR) light, magnetic field and electric current). In addition, they can be developed using different strategies, such as functionalization with signaling molecules, leading to several advantages, such as (a) improved pharmaceutical properties of liposoluble drugs, (b) selectivity with the tumor tissue decreasing systemic toxic effects, (c) controlled release upon different stimuli, which are all fundamental to improving the therapeutic effectiveness of breast cancer treatment. Therefore, this review summarizes the use of stimuli-responsive DDNs in the treatment of breast cancer. We have divided the discussions into intrinsic and extrinsic stimuli and have separately detailed them regarding their definitions and applications. Finally, we aim to address the ability of these stimuli-responsive DDNs to control the drug release in vitro and the influence on breast cancer therapy, evaluated in vivo in breast cancer models.

Plant Extracts Loaded in Nanostructured Drug Delivery Systems for Treating Parasitic and Antimicrobial Diseases.

BACKGROUND: Plant extracts loaded in nanostructured drug delivery systems (NDDSs) have been reported as an alternative to current therapies for treating parasitic and antimicrobial diseases. Among their advantages, plant extracts in NDSSs increase the stability of the drugs against environmental factors by promoting protection against oxygen, humidity, and light, among other factors; improve the solubility of hydrophobic compounds; enhance the low absorption of the active components of the extracts (i.e., biopharmaceutical classification II), which results in greater bioavailability; and control the release rate of the substances, which is fundamental to improving the therapeutic effectiveness. In this review, we present the most recent data on NDDSs using plant extracts and report results obtained from studies related to in vitro and in vivo biological activities.

Nanostructured lipid carriers for incorporation of copper(II) complexes to be used against Mycobacterium tuberculosis.

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. Cessation of treatment before the recommended conclusion may lead to the emergence of multidrug-resistant strains. The aim of this study was to develop nanostructured lipid carriers (NLCs) for use in the treatment of M. tuberculosis. The NLCs comprised the following lipid phase: 2.07% polyoxyethylene 40 stearate, 2.05% caprylic/capric triglyceride, and 0.88% polyoxyl 40 hydrogenated castor oil; the following aqueous phase: 3.50% poloxamer 407 (F1-F6), and 0.50% cetyltrimethylammonium bromide (F7-F12); and incorporated the copper(II) complexes [CuCl2(INH)2]·H2O (1), [Cu(NCS)2(INH)2]·5H2O (2), and [Cu(NCO)2(INH)2]·4H2O (3) to form compounds F11.1, F11.2, and F11.3, respectively. The mean diameter of F11, F11.1, F11.2, and F11.3 ranged from 111.27±21.86 to 134.25±22.72 nm, 90.27±12.97 to 116.46±9.17 nm, 112.4±10.22 to 149.3±15.82 nm, and 78.65±6.00 to 122.00±8.70 nm, respectively. The polydispersity index values for the NLCs ranged from 0.13±0.01 to 0.30±0.09. The NLCs showed significant changes in zeta potential, except for F11.2, with F11, F11.1, F11.2, and F11.3 ranging from 18.87±4.04 to 23.25±1.13 mV, 17.03±1.77 to 21.42±1.87 mV, 20.51±1.88 to 22.60±3.44 mV, and 17.80±1.96 to 25.25±7.78 mV, respectively. Atomic force microscopy confirmed the formation of nanoscale spherical particle dispersions by the NLCs. Differential scanning calorimetry determined the melting points of the constituents of the NLCs. The in vitro activity of copper(II) complex-loaded NLCs against M. tuberculosis H37Rv showed an improvement in the anti-TB activity of 55.4, 27.1, and 41.1 times the activity for complexes 1, 2, and 3, respectively. An in vivo acute toxicity study of complex-loaded NLCs demonstrated their reduced toxicity. The results suggest that NLCs may be a powerful tool to optimize the activity of copper(II) complexes against M. tuberculosis.