Background. Sickle cell anaemia (SCA) is the most prevalent monogenic disease in Brazil. In SCA, haemoglobin S (HbS) is formed, which modifies red blood cell morphology. Intravascular haemolysis occurs, in which free Hb and free radicals degrade nitric oxide (NO) and release arginase, which reduces arginine levels. Because arginine is a substrate for NO formation, this decrease leads to reduced NO (vasodilator) synthesis. SCA treatment uses hydroxyurea (HU) to maintain high foetal haemoglobin (HbF) levels and reduces HbS to avoid haemolytic episodes. Objective. To analyse the efficacy of L-arginine as an adjuvant in the treatment of SCA patients. Setting. The State Blood Centre of Ceará, Brazil. Methods. This was a randomized double-blind clinical study of adults with SCA with continuous use of HU at the State Blood Centre of Ceará. The clinical study enrolled 25 patients receiving HU + L-arginine (500 mg) and 25 patients receiving HU + placebo. The treatment was carried out over four months. Laboratory tests were performed to determine the levels of the following: (1) complete blood count; (2) nitrite + nitrate; (3) HbF; and (4) reticulocytes. The clinical experiments were performed by a haematologist. The main outcome measures were nitrite and pain. Results. Statistical analysis showed that the levels of NO were increased in the study group, and there was also a reduction in pain frequency using a pain frequency scale by day, week, and month. The levels of nitrite plus nitrate in the group receiving placebo plus HU did not change among the times evaluated (38.27 ± 17.27 mg/L, 39.49 ± 12.84 mg/L, 34.45 ± 11.25 mg/L, p >0.05), but in the patients who received supplementation with L-arginine plus HU, a significant increase in nitrite plus nitrate levels was observed between M0 and M4 (36.55 ± 20.23 mg/L versus 48.64 ± 20.63 mg/L, p =0.001) and M2 and M4 (35.71 ± 15.11 mg/L versus 48.64 ± 20.63 mg/L, p <0.001). It is important to note that the increase in nitrite plus nitrate levels occurred only in the fourth month of follow-up of patients in the treatment group, showing that at least 4 months of supplementation with L-arginine is necessary to show an increase in these metabolites in the serum. Conclusion. The use of L-arginine as a coadjuvant in the treatment of sickle cell anaemia may function as a potential tool for pain relief, consequently improving the life of patients.
TiO is a common inorganic filter used in sunscreens due to its photoprotective effect on the skin against UV radiation. However, the use of this kind of material in cosmetics is limited by its inherent photocatalytic activity. It is known that coating on TiO surface can improve some features. Although, many of the methodologies used for this purpose are still laborious and time-consuming. Thus, this work reports a novel, easy, cheap and fast strategy to coat TiO particles by using a sonochemistry approach, aiming to decrease photocatalytic activity and to enhance colloidal stability. For this proposal, SiO, AlO, ZrO and sodium polyacrylate (PAANa) were used to tune the surface of commercial TiO particles and they were applied in a sunscreen formulation. The samples were characterized by XRPD, FT-IR, DLS, EDS, SEM and TEM. The photocatalytic activity and UV-shielding ability were also evaluated. The sunscreen formulations were prepared and characterized by zeta potential, DLS, and Sun Protection Factor (SPF). FT-IR, EDS, and charge surface of the particles confirmed the success of the sonochemistry coating. Additionally, TiO@AlO, TiO@SiO and TiO@PAANa show a lower photocatalytic activity than original TiO with similar UV-shielding ability. The sunscreens produced with the coated TiO have similar SPF to the one with commercial TiO. Specifically, the sunscreen with TiO@PAANa shows an increase in colloidal stability. Herein, the incorporation of the sonochemical-coated TiO particles in sunscreen formulations may produce sunscreens with better aesthetic appearance and a greater health security due to its lower free radicals production.
PREPARATION, PHYSICOCHEMICAL CHARACTERIZATION AND CONTROLLED RELEASE OF GALACTOMANNAN MICROPARTICLES CONTAINING ALLANTOIN. In this work, the allantoin was encapsulated with galactomannan extruded from Delonyx regia, by the spray drying technique. The microparticles obtained were structurally characterized by infrared spectroscopy (IR), thermal analysis, scanning electron microscopy (SEM) and the controlled release profile was evaluated. The results of IR suggested the formation of the polymeric wall of the microcapsules and SEM revealed spherical particles with an average size range of 2.84 ± 0.41 μm. X-ray diffraction showed the loss of crystallinity of the active after encapsulation and differential explanatory calorimetry exhibited the loss of its peak melt. The encapsulation efficiency for the microparticles was approximately 84% for the different environmental conditions. The coating of allantoin with the biopolymer promoted a gradual release of the drug over a period of 6 hours and these results are in accordance with the Brazilian Pharmacopoeia. The set of results obtained in this work is relevant and accredits the system developed as a possible alternative for the formation of encapsulated natural drugs destined to possible treatments of cutaneous cellular regeneration.
Plant phenolic extracts are widely recognized as an important source of natural antioxidant substances and potential compounds for cosmetic formulations. This study aimed to evaluate the chemical profile, photoprotective and antioxidant activities of stem bark extract of Spondias purpurea L. (ciriguela) and its application in photoprotective formulations. Thirty phenolic constituents were annotated by ultra-performance liquid chromatography coupled with an electrospray ionization quadrupole time-of-flight mass spectrometry in mode negative (UPLC‑QTOF-MS2). The stem bark extract antioxidant and chelation potential, expressed in half maximal inhibitory concentration (IC50), showed 6.25 and 352.22 μg mL−1, respectively. The phenolic extract was used as an active ingredient in six sunscreen formulations, with concentrations ranging from 0.2 to 10%. The ultraviolet (UV) protection properties of the formulations were evaluated by sun protection factor (SPF) values obtained in 0.2 mg mL−1 (0.495 to 2.27) and 2.0 mg mL−1 (2.29 to 15.87). The SPF value for the extract (14.37 and 26.16) was high, but there was a reduction in the base formulation. However, these results suggested that the bioactive extracted of stem bark of Spondias purpurea L. has interesting potential to reduce the damage caused by UV radiation and may be utilized as an active ingredient in a sunscreen formulation.
Venom-derived peptides display diverse biological and pharmacological activities, making them useful in drug discovery platforms and for a wide range of applications in medicine and pharmaceutical biotechnology. Due to their target specificities, venom peptides have the potential to be developed into biopharmaceuticals to treat various health conditions such as diabetes mellitus, hypertension, and chronic pain. Despite the high potential for drug development, several limitations preclude the direct use of peptides as therapeutics and hamper the process of converting venom peptides into pharmaceuticals. These limitations include, for instance, chemical instability, poor oral absorption, short halflife, and off-target cytotoxicity. One strategy to overcome these disadvantages relies on the formulation of bioactive peptides with nanocarriers. A range of biocompatible materials are now available that can serve as nanocarriers and can improve the bioavailability of therapeutic and venom-derived peptides for clinical and diagnostic application. Examples of isolated venom peptides and crude animal venoms that have been encapsulated and formulated with different types of nanomaterials with promising results are increasingly reported. Based on the current data, a wealth of information can be collected regarding the utilization of nanocarriers to encapsulate venom peptides and render them bioavailable for pharmaceutical use. Overall, nanomaterials arise as essential components in the preparation of biopharmaceuticals that are based on biological and pharmacological active venom-derived peptides.
This work describes the development and characterization of triglyceride-based magnetic nanocomposites for application in magnetic hyperthermia and controlled drug delivery. The magnetic solid lipid nanocomposites (MSLN) constituted by mixtures of trilaurin-tricaprylin and trilaurin-tricaprin have been successfully obtained by emulsification-solvent evaporation method. The developed MSLNs were subjected to an external oscillating magnetic field and showed significant hyperthermia. The samples were exposed to frequencies of 688 and 869 kHz causing, respectively, a temperature increase of 15.5 and 22.7 °C (trilaurin-tricaprylin) and 17.3 and 26.1 °C (trilaurin-tricaprin). Also, in vitro assays in the absence of magnetic field showed that the triglyceride-based formulations were able first to encapsulate and then to sustained release an antitumoural hydrophobic drug. After 72 h of assay trilaurin-tricaprylin and trilaurin-tricaprin released 73 and 55% of their cargo, respectively. In addition, MSLN exhibited low in vitro cytotoxic activity against human neutrophils.Keywords: lipid mixture, magnetic hyperthermia, drug delivery, oncocalyxone-A IntroductionNanotechnology is an expanding sector and the use of superparamagnetic iron oxide nanoparticles (SPIONs) is attracting increasing attention in several areas. SPIONs are widely employed for biotechnological applications through the development of magnetic systems for use in: cell separation, as contrast agents for magnetic resonance imaging (MRI), magnetic hyperthermia, targeted bioactive compounds delivery and biosensors. [1][2][3][4] Such applications explore the biggest advantages of using SPIONs: biocompatibility and satisfactory magnetic response at applied magnetic field (superparamagnetic character). 5,6 The surface of the magnetic nanoparticles should be modified, not only in order to prevent oxidation and aggregation, but also to provide colloidal stability, reduced magnetic susceptibility, as well as to expand the effectiveness of cellular uptake and biodistribution. The hydroxyl groups present on the surface of nanoparticles can function as an anchor point for various types of compounds such as oleic acid, which is commonly used in the synthesis of magnetic ferrofluids. The criteria adopted to select the appropriate coating of magnetic nanoparticles depends mainly on the intended application. In the case of this research, magnetic nanoparticles made of iron oxide were coated with oleic acid (Fe 3 O 4 @OA) for subsequent incorporation into lipid carriers. 7-9The lipid carriers have been widely used as they also possess excellent characteristics such as biocompatibility Preliminary Evaluation of Novel Triglyceride-Based Nanocomposites for Biomedical Applications J. Braz. Chem. Soc. 1548 and versatility, and they have been proposed for the delivery of bioactive compounds by oral, intravenous, topical and parenteral routes. 10,11The solid lipid nanoparticles (SLNs) emerged in the early 90's and currently are alternative encapsulation systems and carriers o...
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