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The blood-brain barrier (BBB) is a barrier that separates the blood from the brain tissue and possesses unique characteristics that make the delivery of drugs to the brain a great challenge. To achieve this purpose, it is necessary to design strategies to allow BBB passage, in order to reach the brain and target the desired anatomic region. The use of nanomedicine has great potential to overcome this problem, since one can modify nanoparticles with strategic molecules that can interact with the BBB and induce uptake through the brain endothelial cells and consequently reach the brain tissue. This review addresses the potential of nanomedicines to treat neurological diseases by using nanoparticles specially developed to cross the BBB.

Breast cancer is the leading cause of cancer-related deaths among women worldwide. The conventional chemotherapeutic regimens used in the treatment of this disease often lead to severe side-effects and reduced efficacy. In this study, a novel drug delivery system for the chemotherapeutic drug mitoxantrone (Mito) was developed using solid lipid nanoparticles (SLN). The production of the SLN was carried out using an organic-solvent-free, low-cost method and optimized using a Box-Behnken design. SLN presented adequate size for cancer-related applications, more than 90% of EE% and remained stable for at least 6 months. A much higher drug release was obtained at acidic pH (mimicking the endosomal compartment) than plasmatic pH, highlighting the potential of the nanosystem for tumor drug delivery. Additionally, SLN were non-hemolytic and cytocompatible, even at high concentrations of lipid. A significantly higher anti-cancer efficacy was obtained for Mito-loaded SLN comparing to the free drug at different concentrations in MCF-7 2D models. Finally, the nanoformulation was evaluated in heterotypic breast cancer spheroids showing capacity to penetrate the tridimensional structure and ability to induce a high anti-tumoral effect, similarly to the free drug. Overall, these results support that the developed SLN are effective Mito nanocarriers for the treatment of breast cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Curcumin is an anti-inflammatory and antioxidant compound with potent neuroprotective activity. Due to its poor water solubility, low bioavailability, rapid elimination and the challenges for crossing and transposing the blood-brain barrier (BBB), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with curcumin were successfully produced and functionalized with transferrin, in order to mediate the transport of these particles through the BBB endothelium to the brain. The nanosystems revealed Z-averages under 200 nm, polydispersity index below 0.2 and zeta potential around -30 mV. Curcumin encapsulation around 65 % for SLNs and 80 % for NLCs was accomplished, while the functionalized nanoparticles presented a value around 70-75 %. A stability study revealed these characteristics remained unchanged for at least 3 months. hCMEC/D3 cells viability was firstly analysed by MTT and LDH assays, respectively, and a concentration of 10 μM of curcumin-loaded nanoparticles were then selected for the subsequent permeability assay. The permeability study was conducted using transwell devices with hCMEC/D3 cells monolayers and a 1.5-fold higher permeation of curcumin through the BBB was verified. Both SLNs and NLCs are promising for curcumin brain delivery, protecting the incorporated curcumin and targeting to the brain by the addition of transferrin to the nanoparticles surface., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This work proposes the development and characterization of solid lipid nanoparticles (SLNs) loaded with rifampicin (RIF) aiming to enhance mucoadhesion of the SLNs and consequently internalization by the alveolar macrophages (AMs). The lipid nanoparticles (NPs) were characterized and the results showed that the NPs obtained present a spherical or a starry shape with diameter around 250-500 nm, a monodisperse population, with zeta potential between -31 mV for uncoated SLNs and +33 mV for coated SLNs. The drug EE was approximately 90 % and the loading capacity (LC) 4.5 %. The SLNs coated with chitosan by the association method (aC-SLNs) show an effective mucoadhesive profile, verified by the turdimetry and surface loading method, corroborated with the cellular assays. The presence of chitosan in the aC-SLNs promotes higher mucoadhesive properties to the NPs and permeability in A549, suggesting that the safe aC-SLNs-RIF can be used as a promising drug delivery system for improving tuberculosis treatment., (Copyright © 2020. Published by Elsevier Ltd.)

Quercetin was encapsulated in lipid nanoparticles (SLN and NLC) to take advantage of its neuroprotective properties in Alzheimer's disease. The nanoparticles were functionalized with transferrin to facilitate the passage across the blood-brain barrier through the transferrin receptors overexpressed in brain endothelial cells. NMR and FTIR confirmed the functionalization of the nanoparticles with transferrin. TEM results showed all nanoparticles presented spherical morphology. Nanoparticles exhibited size around 200 nm and zeta potential values higher than -30 mV. Quercetin entrapment efficiency was around 80-90%. LDH cytotoxicity assays in hCMEC/D3 cell line demonstrated that even for the highest concentration (30 μM) nanoparticles did not reveal cytotoxicity after 4 h of incubation. Permeability studies across hCMEC/D3 cell monolayers showed NLC permeate more the blood-brain barrier, while amyloid-beta studies demonstrated NLC-transferrin have the capacity to inhibit fibril formation. Nanoparticles seem to be suitable for brain applications, mainly for Alzheimer's disease due to inhibition of amyloid-beta aggregation., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Taking into consideration the potential mucoadhesion properties of systems in lung delivery, this paper describes the preparation and characterization of chitosan-coated solid lipid nanoparticles (C-SLNs) loaded with rifampicin (RIF) as anti-tuberculosis (anti-TB) drug. The process of development and characterization of the NPs in terms of size, surface charge, encapsulation efficiency (EE), morphology, in vitro drug release, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), in vitro assessment of mucoadhesive property, cell viability and permeability studies are documented. Results showed that the SLNs had a smooth spherical shape with a size of ca. 245-344 nm and with a zeta potential around -30 mV for SLNs and +40 mV for C-SLNs. The surface charge variation from negative to positive charge and FTIR analysis demonstrated the successful process of coating the nanoparticles (NPs) surface with chitosan. The DSC thermograms were in agreement with the nanostructure of the SLNs. The EE of drug was found to be higher than 90% and the loading capacity (LC) around 4.5%. C-SLNs show higher in vitro muchoadesive properties and a higher permeability in alveolar epithelial cells A549 than uncoated SLNs, indicating that the developed C-SLNs can be used as a promising carrier for sasfer and efficient management of TB., (Copyright © 2017. Published by Elsevier B.V.)

Tuberculosis (TB) is still a devastating disease and more people have died of TB than any other infectious diseases throughout the history. The current therapy consists of a multidrug combination in a long-term treatment, being associated with the appearance of several adverse effects. Thus, solid lipid nanoparticles (SLNs) were developed using mannose as a lectin receptor ligand conjugate for macrophage targeting and to increase the therapeutic index of rifampicin (RIF). The developed SLNs were studied in terms of diameter, polydispersity index, zeta potential, encapsulation efficiency (EE) and loading capacity (LC). Morphology, in vitro drug release and differential scanning calorimetry studies, macrophage uptake studies, cell viability and storage stability studies were also performed. The diameter of the SLNs obtained was within the range of 160-250 nm and drug EE was above 75%. The biocompatibility of M-SLNs was verified and the internalization in macrophages was improved with the mannosylation. The overall results suggested that the developed mannosylated formulations are safe and a promising tool for TB therapy targeted for macrophages.

Aim: This work aims to develop a mannosylated nanostructured lipid carrier (NLC) loaded with rifampicin to improve tuberculosis treatment., Materials & Methods: An active targeting strategy was used and the nanoparticles were characterized. Effects on cell viability and the antimycobacterial activity of the nanoformulations were evaluated., Results: The nanoparticles developed exhibited a size of about 315 nm and polydispersity <0.2. The drug encapsulation efficiency was higher than 90% and its release was sensitive to pH. The mannosylated NLCs showed efficient uptake by bone marrow derived macrophages. Further, rifampicin-loaded mannosylated NLCs were more efficient in inducing a decrease of intracellular growth of mycobacteria., Conclusion: The NLCs developed can be used as a promising carrier for safer and efficient management of tuberculosis.

We tested the efficiency of 2 different antibiotics, rifampicin and oxolinic acid, against an established infection caused by fish pathogen Francisella noatunensis ssp. orientalis (F.n.o.) in zebrafish. The drugs were tested in the free form as well as encapsulated into biodegradable nanoparticles, either polylactic-co-glycolic acid (PLGA) nanoparticles or nanostructured lipid carriers. The most promising therapies were PLGA-rifampicin nanoparticles and free oxolinic acid; the PLGA nanoparticles significantly delayed embryo mortality while free oxolinic acid prevented it. Encapsulation of rifampicin in both PLGA and nanostructured lipid carriers enhanced its efficiency against F.n.o. infection relative to the free drug. We propose that the zebrafish model is a robust, rapid system for initial testing of different treatments of bacterial diseases important for aquaculture.

Nowadays, the society is facing a large health problem with the rising of new diseases, including cancer, heart diseases, diabetes, neurodegenerative diseases, and obesity. Thus, it is important to invest in substances that enhance the health of the population. In this context, epigallocatechin gallate (EGCG) is a flavonoid found in many plants, especially in tea. Several studies support the notion that EGCG has several benefits in fighting cancer, heart diseases, diabetes, and obesity, among others. Nevertheless, the poor intestinal absorbance and instability of EGCG constitute the main drawback to use this molecule in prevention and therapy. The encapsulation of EGCG in nanocarriers leads to its enhanced stability and higher therapeutic effects. A comprehensive review of studies currently available on the encapsulation of EGCG by means of nanocarriers will be addressed.

Green tea is manufactured from the leaves of Camellia sinensis and has been shown to possess, among other properties, anticancer, antiobesity, antiatherosclerotic, antidiabetic, antibacterial, and antiviral effects. The beneficial effects of green tea are related to the activities of (-)-epigallocatechin gallate (EGCG). This catechin is very unstable, undergoing degradation and epimerization, which is responsible for the loss of its health benefits. Encapsulation in nanoparticles (NPs) is an effective method to protect EGCG from adverse environmental conditions. In this work, solid lipid NPs (SLN) and nanostructured lipid carriers (NLC) were successfully developed to be used as biocompatible nanocarriers, enhancing the stability of EGCG. The mean diameter of the NPs was found to be around 300-400 nm, which is suitable for oral administration. Moreover, EGCG was effectively encapsulated with a remarkable efficiency of encapsulation of 80% and 90% for SLN and NLC, respectively. In addition, high storage stability of the formulations is expected as they maintain the initial characteristics for 3 months. Limited release of EGCG from the NPs was observed in simulated gastric and intestinal fluids. MTT and lactate dehydrogenase (LDH) assays demonstrated that NPs possess low toxicity, and so have potential to be used for preventive and therapeutic EGCG supplementation., Competing Interests: The authors report no conflicts of interest in this work.

This work aimed to design, develop, and characterize a lipid nanocarrier system for the selective delivery of rifabutin (RFB) to alveolar macrophages. Lipid nanoparticles, specifically nanostructured lipid carriers (NLC), were synthetized by the high-shear homogenization and ultrasonication techniques. These nanoparticles were designed to exhibit both passive and active targeting strategies to be efficiently internalized by the alveolar macrophages, traffic to the acidified phagosomes and phagolysosomes, and release bactericidal concentrations of the antituberculosis drug intracellularly. NLC that could entrap RFB were prepared, characterized, and further functionalized with mannose. Particles' diameter, zeta potential, morphology, drug% entrapping efficiency, and drug release kinetics were evaluated. The mannose coating process was confirmed by Fourier transform infrared. Further, the cytotoxicity of the formulations was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay in A549, Calu-3, and Raw 264.7 cells. The diameter of NLC formulations was found to be in the range of 175-213 nm, and drug entrapping efficiency was found to be above 80%. In addition, high storage stability for the formulations was expected since they maintained the initial characteristics for 6 months. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. These results pose a strong argument that the developed nanocarrier can be explored as a promising carrier for safer and more efficient management of tuberculosis by exploiting the pulmonary route of administration.

The aim of the present work was to develop and optimize surface-functionalized solid lipid nanoparticles (SLNs) for improvement of the therapeutic index of dapsone (DAP), with the application of a design of experiments. The formulation was designed to target intestinal microfold (M-cells) as a strategy to increase internalization of the drug by the infected macrophages. DAP-loaded SLNs and mannosylated SLNs (M-SLNs) were successfully developed by hot ultrasonication method employing a three-level, three-factor Box-Behnken design, after the preformulation study was carried out with different lipids. All the formulations were systematically characterized regarding their diameter, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and loading capacity. They were also subjected to morphological studies using transmission electron microscopy, in vitro release study, infrared analysis (Fourier transform infrared spectroscopy), calorimetry studies (differential scanning calorimetry), and stability studies. The diameter of SLNs, SLN-DAP, M-SLNs, and M-SLN-DAP was approximately 300 nm and the obtained PDI was <0.2, confirming uniform populations. Entrapment efficiency and loading capacity were approximately 50% and 12%, respectively. Transmission electron microscopy showed spherical shape and nonaggregated nanoparticles. Fourier transform infrared spectroscopy was used to confirm the success of mannose coating process though Schiff's base formation. The variation of the ZP between uncoated (approximately -30 mV) and mannosylated formulations (approximately +60 mV) also confirmed the successful coating process. A decrease in the enthalpy and broadening of the lipid melting peaks of the differential scanning calorimetry thermograms are consistent with the nanostructure of the SLNs. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. Storage stability for the formulations for at least 8 weeks is expected, since they maintain the original characteristics of diameter, PDI, and ZP. These results pose a strong argument that the developed formulations can be explored as a promising carrier for treating leprosy with an innovative approach to target DAP directly to M-cells.

Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (-)-Epigallocatechin-3-gallate (EGCG) is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG's properties and potentiate its anti-tumoral activity.

Purpose: Lipid nanoparticles (SLN and NLC) were functionalized with the RVG29 peptide in order to target the brain and increase the neuronal uptake through the nicotinic acetylcholine receptors. These nanosystems were loaded with quercetin to take advantage of its neuroprotective properties mainly for Alzheimer's disease. Methods: The functionalization of nanoparticles with RVG29 peptide was confirmed by NMR and FTIR. Their morphology was assessed by transmission electron microscopy and nanoparticles size, polydispersity and zeta potential were determined by dynamic light scattering. The in vitro validation tests were conducted in hCMEC/D3 cells, a human blood-brain barrier model and thioflavin T binding assay was conducted to assess the process of amyloid-beta peptide fibrillation typical of Alzheimer's disease. Results: RVG29-nanoparticles displayed spherical morphology and size below 250 nm, which is compatible with brain applications. Zeta potential values were between −20 and −25 mV. Quercetin entrapment efficiency was generally higher than 80% and NLC nanoparticles were able to encapsulate up to 90%. The LDH assay showed that there is no cytotoxicity in hCMEC/D3 cell line and RVG29-nanoparticles clearly increased in 1.5-fold the permeability across the in vitro model of blood-brain barrier after 4 h of incubation compared with non-functionalized nanoparticles. Finally, this nanosystem was capable of inhibiting amyloid-beta aggregation in thioflavin T binding assay, suggesting its great potential for neuroprotection. Conclusions: RVG29-nanoparticles that simultaneously target the blood-brain barrier and induce neurons protection against amyloid-beta fibrillation proved to be an efficient way of quercetin delivery and a promising strategy for future approaches in Alzheimer's disease. [ABSTRACT FROM AUTHOR]