Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases

Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) comprise a category of versatile drug delivery systems that have been used in the biomedical field for > 25 years. SLNs and NLCs have been used for the treatment of various diseases including cardiovascular and cerebrovascular, and are considered a standard treatment for the latter, due to their inherent ability to cross the blood brain barrier (BBB). In this review, a presentation of the most important brain diseases (brain cancer, ischemic stroke, Alzheimer's disease, Parkinson's disease and multiple sclerosis) is approached, followed by the basic fabrication techniques of SLNs and NLCs. A detailed description of the reported studies of the last seven years, of active and passive targeting SLNs and NLCs for the treatment of glioblastoma multiforme and of other brain cancers, as well as for the treatment of neurodegenerative diseases is also carried out. Finally, a brief description of the advantages, the disadvantages, and the future perspectives in the use of these nanocarriers is reported, aiming at giving an insight of the limitations that have to be overcome in order to result in a delivery system with high therapeutic efficacy and without the limitations of the existing nano-systems

Natural Antioxidant Compounds as Potential Pharmaceutical Tools against Neurodegenerative Diseases

Natural antioxidants are a very large diversified family of molecules classified by activity (enzymatic or nonenzymatic), chemical-physical properties (e.g., hydrophilic or lipophilic), and chemical structure (e.g., vitamins, polyphenols, etc.). Research on natural antioxidants in various fields, such as pharmaceutics, nutraceutics, and cosmetics, is among the biggest challenges for industry and science. From a biomedical point of view, the scavenging activity of reactive oxygen species (ROS) makes them a potential tool for the treatment of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, dementia, and amyotrophic lateral sclerosis (ALS). In addition to the purified phytochemical compounds, a variety of natural extracts characterized by a complex mixture of antioxidants and anti-inflammatory molecules have been successfully exploited to rescue preclinical models of these diseases. Extracts derived from Ginkgo biloba, grape, oregano, curcumin, tea, and ginseng show multitherapeutic effects by synergically acting on different biochemical pathways. Furthermore, the reduced toxicity associated with many of these compounds limits the occurrence of side effects. The support of nanotechnology for improving brain delivery, controlling release, and preventing rapid degradation and excretion of these compounds is of fundamental importance. This review reports on the most promising results obtained on in vitro systems, in vivo models, and in clinical trials, by exploiting natural-derived antioxidant compounds and extracts, in their free form or encapsulated in nanocarriers

Biomolecular Corona Associated with Nanostructures: The Potentially Disruptive Role of Raman Microscopy

AbstractWhen nanostructures and other materials are exposed to biological fluids, they are immediately covered by a layer of biological molecules, which is typically referred to as a "biomolecular corona" (BC). This represents the first component of a material that interacts with biological systems, so characterizing the composition and the dynamic evolution of BC is essential for predicting the interactions of materials and living organisms. This review provides an analysis of current BC characterization techniques, with particular attention to nanostructures involved in biomedical applications. The influence on cell–nanostructure interactions is assessed and the advantages and limitations of each technique are discussed and compared. An in‐depth analysis of Raman microscopy, a relatively unexploited tool with great potential in the characterization of BC, is then conducted. Raman microscopy can be used to analyze a vast amount of specimens without the need for staining, and can provide analysis on a spatial scale of hundreds of nanometers: it may thus represent a potentially disruptive tool for the characterization of BC, as it overcomes many of the limitations posed by current techniques

Innovative nanotechnology tools for the functional control and tracking of human stem cells

The precise control of stem cell behavior, including differentiation, transdifferentiation, and reprog-ramming, is fundamental for safely and efficiently using human stem cells in regenerative medicine. Thanks to recent innovations and developments in the field of nanomedicine, as well as its integration with advanced molecular biology approaches, the possibility of engineering and restoring functions of complex tissues become reality. Multifunctional nanotechnological tools allow to finely control the release of growth factors, mRNA, and other molecules, to promote cell fate conversion, and to perform long-term tracking in vivo. Furthermore, stimulation approaches based on smart and biocompatible nanotransducers promise to remotely modulate the stem cell activity, paving the way for the actual exploitation of these technologies in the internal tissues of large-sized animals. In this review, the most innovative nanotechnology tools applied to stem cell-based regenerative medicine are presented, and their implications for future research and clinics are discussed.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

Ultrasound-Activated Piezoelectric Nanoparticles Inhibit Proliferation of Breast Cancer Cells

Abstract A nanotechnology-based approach for the inhibition of breast cancer cell proliferation is proposed. The innovative solution consists in a platform based on biocompatible piezoelectric nanoparticles able to target and remotely stimulate HER2-positive breast cancer cells. The anti-proliferative effects of the ultrasound-driven piezoelectric nanoparticle-assisted stimulation significantly reduced the proliferation by inducing the cell cycle arrest. Similarly to a low-intensity alternating electric field, chronic piezoelectric stimulation resulted able to inhibit cancer cell proliferation by upregulating the expression of the gene encoding Kir3.2 inward rectifier potassium channels, by interfering on Ca2+ homeostasis, and by affecting the organization of mitotic spindles during mitosis. The proposed platform, even if specific for HER2-positive cells, shows huge potential and versatility for the treatment of different type of cancers

Clinical significance of inflammatory markers of bacterial infection in critically ill patients with COVID-19 after treatment with anti-inflammatory and immunomodulatory drugs: a complex new scenario.

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CeO2 Nanoparticles-Loaded pH-Responsive Microparticles with Antitumoral Properties as Therapeutic Modulators for Osteosarcoma

Osteosarcoma is an aggressive form of bone cancer mostly affecting young people. To date, the most effective strategy for the treatment of osteosarcoma is the surgical removal of the tumor with or without combinational chemotherapy. In this study, we present the development of a pH-sensitive drug-delivery system in the form of microparticles, with increased chemotherapeutic action against the osteosarcoma cell line SAOS-2, and with reduced toxicity against the heart myoblastic cell line H9C2. The delivery system is composed of calcium carbonate and collagen type I, and is loaded with cerium dioxide (CeO2) nanoparticles (<25 nm) and the anticancer drug doxorubicin. The fabricated microparticles were fully characterized morphologically and physicochemically, and their ability to induce or inhibit apoptosis/necrosis was assessed using in vitro functional assays and flow cytometry. The results presented in this study show that the highest concentration (250 μg/mL) of the therapeutic microparticles (CaCO3-based therapeutic modulators (C-TherMods)), which corresponds to 6.4 μg/mL of encapsulated doxorubicin, can protect the H9C2 cells even after 120 h, since the percentage of viable cells at this time point is 65%. On the contrary, when H9C2 cells are treated with 0.5 μg/mL of free doxorubicin, 75% of the cells are dead only after 24 h. When SAOS-2 cells are treated with the same concentration of C-TherMods (250 μg/mL), the viability of SAOS-2 cells is 80% after 24 h, while it reduces to 50% after 120 h. At pH 6.0, the synergic effect of the pro-oxidant CeO2nanoparticles and of the encapsulated doxorubicin leads to almost 100% of cell death, even at the lowest concentration of C-TherMods (50 μg/mL)

A 3D Real-Scale, Biomimetic, and Biohybrid Model of the Blood-Brain Barrier Fabricated through Two-Photon Lithography

The investigation of the crossing of exogenous substances through the blood-brain barrier (BBB) is object of intensive research in biomedicine, and one of the main obstacles for reliable in vitro evaluations is represented by the difficulties at the base of developing realistic models of the barrier, which could resemble as most accurately as possible the in vivo environment. Here, for the first time, a 1:1 scale, biomimetic, and biohybrid BBB model is proposed. Microtubes inspired to the brain capillaries were fabricated through two-photon lithography and used as scaffolds for the co-culturing of endothelial-like bEnd.3 and U87 glioblastoma cells. The constructs show the maturation of tight junctions, good performances in terms of hindering dextran diffusion through the barrier, and a satisfactory trans-endothelial electrical resistance. Moreover, a mathematical model is developed, which assists in both the design of the 3D microfluidic chip and its characterization. Overall, these results show the effective formation of a bioinspired cellular barrier based on microtubes reproducing brain microcapillaries to scale. This system will be exploited as a realistic in vitro model for the investigation of BBB crossing of nanomaterials and drugs, envisaging therapeutic and diagnostic applications for several brain pathologies, including brain cancer