ABSTRACT
The blood-brain barrier (BBB) restricts the access of therapeutic agents to the brain, complicating the treatment of neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), glioma, etc. To overcome this limitation and improve drug delivery to the central nervous system (CNS), the potential of nanocarriers, including lipid-based nanosystems, has been explored. Through active targeting, the surface of the nanocarriers can be modified with ligands that interact with the BBB, enhancing their uptake and penetration across the brain endothelium by different physiological mechanisms, such as receptor- or transporter-mediated transcytosis. This review seeks to provide an overview of active targeting in brain delivery, while highlighting the potential of functionalized lipid nanocarriers to treat brain diseases. Therefore, in the first sections, we discuss the importance of active targeting in CNS drug delivery, present the different ligands commonly used for functionalization, as well as summarize the state of the art of the most recent and relevant studies of surface-modified lipid nanosystems developed for neurological disorders. Lastly, challenges hindering clinical translation are discussed, and critical insights and future perspectives outlined. Although some limitations have been identified, it is expected that in the upcoming years these nanosystems will be an established approach.
Subject(s)
Alzheimer Disease , Nanoparticles , Humans , Blood-Brain Barrier , Ligands , LipidsABSTRACT
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood-brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94-98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 µM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain.
ABSTRACT
Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these disorders and create new and better strategies to improve bioavailability and therapeutic efficiency, such as nanocarriers. Microfluidics is an intersectional field with many applications. Microfluidic systems can be an invaluable tool to accurately simulate the BBB microenvironment, as well as develop, in a reproducible manner, drug delivery systems with well-defined physicochemical characteristics. This review provides an overview of the most recent advances on microfluidic devices for CNS-targeted studies. Firstly, the importance of the BBB will be addressed, and different experimental BBB models will be briefly discussed. Subsequently, microfluidic-integrated BBB models (BBB/brain-on-a-chip) are introduced and the state of the art reviewed, with special emphasis on their use to study NDs. Additionally, the microfluidic preparation of nanocarriers and other compounds for CNS delivery has been covered. The last section focuses on current challenges and future perspectives of microfluidic experimentation.
ABSTRACT
Different colored jasper samples from Brazilian mines were powdered and mixed with teflon (composites jasper-teflonTM). This paper describes a preliminary study of a thermoluminescent method (TL) to verify the possibility of their use as high dose dosimeters or irradiation indicators in industrial areas. The jasper samples were exposed to different radiation doses, using the gamma-cell 220 system (60Co) of IPEN. The TL emission curves of samples presented two peaks at 130 °C and 190 °C. Calibration curves were obtained for the jasper samples between 50 Gy and 20 kGy. All five types of jasper samples showed their usefulness as irradiation indicators and as high-dose dosimeters.
ABSTRACT
The dosimeter characteristics of jade samples were studied for application in high-dose dosimetry. Jade is the common denomination of two silicates: jadeite and actinolite. The EPR spectra of different jade samples were obtained after irradiation with absorbed doses of 100 Gy up to 20 kGy. The jade samples present signals that increase with the absorbed dose (g-factors around 2.00); they can be attributed to electron centers. The EPR spectra obtained for the USA jade samples and their main dosimetric properties as reproducibility, calibration curves and energy dependence were investigated.
Subject(s)
Electron Spin Resonance Spectroscopy/methods , Radiometry/methods , Silicates/analysis , Silicates/chemistry , Materials TestingABSTRACT
The dosimetric properties of sand from Brazilian beaches have shown to be useful for high-dose dosimetry. The thermoluminescent (TL) and electron paramagnetic resonance (EPR) techniques were utilised, and the sand samples were recently studied in relation to their main dosimetric properties. The EPR signal at g = 1.999 grows significantly in function of the absorbed dose, and the TL peaks appear at 110 and 170 degrees C. However, these sand samples present a post-irradiation thermal decay at room temperature, which is a problem for dosimetric procedures. In this study, sand samples have been studied in relation to different thermal treatments. Post-irradiation treatments were performed at 50 degrees C up to 230 degrees C.
Subject(s)
Silicon Dioxide/chemistry , Silicon Dioxide/radiation effects , Thermoluminescent Dosimetry/instrumentation , Thermoluminescent Dosimetry/methods , Dose-Response Relationship, Radiation , Equipment Design , Equipment Failure Analysis , Hot Temperature , Materials Testing , Radiation Dosage , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The electronic paramagnetic resonance (EPR) technique was utilized to study sand samples from different Brazilian beaches for high-dose dosimetry. Sand also contains concentrations of heavy minerals. Sand samples were studied in relation to their main dosimetric properties: response reproducibility, reutilization, batch uniformity, detection range and dose response. The EPR signal grows significantly as a function of absorbed dose for g=1.999. All studied sand samples can be used as EPR dosimeters for different applications in medical, agricultural and industrial areas.
ABSTRACT
Commercial transparent and colored (bronze, brown, and green) glasses were studied as possible dosimeters for high gamma doses using electronic paramagnetic resonance (EPR). All EPR spectra showed the characteristic Fe3+ signals, g=4.27 and 2.01. The signal at g=2.01 presented a more useable behavior for the calibration curve. All samples showed their usefulness as high dose dosimeters.
ABSTRACT
Coloured glasses produced commercially by Cebracê, São Paulo, were analysed by the thermoluminescent (TL) method, to verify the possibility of their use as high-dose dosemeters or irradiation indicators in industrial areas, due to their easy handling and their low cost. The samples were exposed to different radiation doses, using the Gamma-Cell 220 system (60Co) of IPEN. The TL emission curves presented main peaks at 135, 150 and 145 degrees C in the bronze, brown and green glass samples, respectively. Calibration curves were obtained for the glasses between 50 Gy and 360 kGy. Reproducibility of TL response and the lower detection doses were determined for each kind of glass. All tested glasses showed their usefulness as irradiation indicators and as high-dose dosemeters.
Subject(s)
Gamma Rays , Glass/radiation effects , Thermoluminescent Dosimetry/instrumentation , Calibration , Cobalt Radioisotopes , Color , Dose-Response Relationship, Radiation , Glass/chemistry , Hot Temperature , Materials Testing , Neutron Activation Analysis , Radiation Dosage , Reproducibility of ResultsABSTRACT
Brazilian commercial glasses of various colors (bronze, brown and green) have been studied to evaluate their potential as radiation-sensitive materials in gamma high-dose dosimetry. Characteristics of their optical absorption responses (reproducibility, room temperature stability, and calibration curves) have been obtained using a spectrophotometer and a simple densitometer specially designed for glass samples. The glass spectra feature a decay at room temperature that has to be taken into consideration. The results show that the colored glasses can be used in dosimetry; the upper limit of the dose range depends on the glass type.
