Genotoxicity Assessment of Metal-Based Nanocomposites Applied in Drug Delivery

Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for several applications in the biomedical field, from therapeutics to diagnostics. Green nanocomposites stand for nanoparticles of biocompatible, biodegradable and non-toxic profiles. When using metal nanoparticles for drug delivery, the question of how hazardous these “virus-sized particles” can be is posed, due to their nanometer size range with enhanced reactivity compared to their respective bulk counterparts. These structures exhibit a high risk of being internalized by cells and interacting with the genetic material, with the possibility of inducing DNA damage. The Comet Assay, or Single-Cell Gel Electrophoresis (SCGE), stands out for its capacity to detect DNA strand breaks in eukaryotic cells. It has huge potential in the genotoxicity assessment of nanoparticles and respective cells’ interactions. In this review, the Comet assay is described, discussing several examples of its application in the genotoxicity evaluation of nanoparticles commonly administered in a set of routes (oral, skin, inhaled, ocular and parenteral administration). In the nanoparticles boom era, where guidelines for their evaluation are still very limited, it is urgent to ensure their safety, alongside their quality and efficacy. Comet assay or SCGE can be considered an essential tool and a reliable source to achieve a better nanotoxicology assessment of metal nanoparticles used in drug delivery.

Lipid Nanoparticles Loaded with Iridoid Glycosides: Development and Optimization Using Experimental Factorial Design

Lipid nanoparticles based on multiple emulsion (W/O/W) systems are suitable for incorporating hydrophilic active substances, including iridoid glycosides. This study involved optimization of composition of lipid nanoparticles, incorporation of active compounds (aucubin and catalpol), evaluation of stability of the resulting nanocarriers, and characterization of their lipid matrix. Based on 32 factorial design, an optimized dispersion of lipid nanoparticles (solid lipid:surfactant—4.5:1.0 wt.%) was developed, predisposed for the incorporation of iridoid glycosides by emulsification-sonication method. The encapsulation efficiency of the active substances was determined at nearly 90% (aucubin) and 77% (catalpol). Regarding the stability study, room temperature was found to be the most suitable for maintaining the expected physicochemical parameter values (particle size < 100 nm; polydispersity index < 0.3; zeta potential > |± 30 mV|). Characterization of the lipid matrix confirmed the nanometer size range of the resulting carriers (below 100 nm), as well as the presence of the lipid in the stable β’ form.

Control of Particle Size in Flame Spray Pyrolysis of Tb–doped Y2O3 for Bio-Imaging

Recently, the use of oxide-based nanomaterials for bio-imaging has received great attention owing to their remarkable stabilities as compared to those of conventional organic dyes. Therefore, the development of scalable methods for highly luminescent oxide materials with fine control of size has become crucial. In this study, we suggested modified flame spray pyrolysis (FSP) as a scalable method to produce a green-light emitting phosphor—Tb–doped Y2O3—in the nanometer size range. In our FSP method, an alkali salt (NaNO3) was found to be highly effective as a size-controlling agent when it is simply mixed with other metal nitrate precursors. The FSP of the mixture solution resulted in oxide composites of Y2O3:Tb3+ and NaxO. However, the sodium by-product was easily removed by washing with water. This salt-assisted FSP produced nano-sized and well-dispersed Y2O3:Tb3+ nanoparticles; their crystallinity and luminescence were higher than those of the bulk product made without the addition of the alkali salt. The nanoparticle surface was further coated with silica for biocompatibility and functionalized with amino groups for the attachment of biological molecules.

Miniaturized, Lightweight, Cost-effective and Fast Response Particle Classifier

&lt;p&gt;Aerosol particles properties depend strongly on their particle size and they have significant effects on both, human health and environment. Nanometer sized particles possess special electrical, optical, and/or magnetic properties. This is one of the reasons which started the interest towards studying aerosol particles in the nanometer size range (Chen and Pui, 1995). The most efficient tool for determining the size of aerosol particle in the sub-micrometer and nanometer range is the differential mobility analyzer (DMA). This popular tool has two coaxial cylindrical electrodes between of them a potential difference is applied and forces the charged polydisperse aerosol to migrate from one electrode to another. Only those particles which have an electrical mobility in a narrow range, the will pass through the classifier (Stolzenburg, 1988).&amp;#160; &amp;#160;Classifying aerosols according to their electrical mobility dates back to the first half of the 20&lt;sup&gt;th&lt;/sup&gt; century and from that time plethora different DMAs have been build and their performances have been tested according to their transfer function and size resolution. One major limitation of classical DMAs is the time it takes to scan over the entire size range to get the size distribution of the aerosol. This is especially leading to the loss of information if the aerosol is changing its size and/or concentration rapidly. This happens for instance during new particle formation events, or also when the measurement takes place on fast moving platforms, such as cars, or airplanes.&lt;/p&gt;&lt;p&gt;The present work evaluates the performance of two different, newly developed DMA types, that aim towards overcoming this limitation. This is done by replacing the classic design of a single monodisperse outlet DMA to a multiple monodisperse outlet DMA. In our case the DMAs have three monodisperse outlets and are 3D-printed (namely, the 3MO-DMA) (Chen et al., 2007; Giamarelou et al., 2012; Barmpounis et al., 2016; Bezantakos et al., 2016). The 3MO-DMA is not only a fast response instrument able to sizing three different sizes ranges at the same time but also is a cost-effective and lightweight instrument suitable to get measurements not only ground based but also on Unmanned Aerial Vehicles or balloons.&lt;/p&gt;

Alginate Nanoparticles for Drug Delivery and Targeting

Nanotechnology refers to the control, manipulation, study and manufacture of structures and devices at the nanometer size range. The small size, customized surface, improved solubility and multi-functionality of nanoparticles will continue to create new biomedical applications, as nanoparticles allow to dominate stability, solubility and bioavailability, as well controlled release of drugs. The type of a nanoparticle, and its related chemical, physical and morphological properties influence its interaction with living cells, as well as determine the route of clearance and possible toxic effects. This field requires cross-disciplinary research and gives opportunities to design and develop multifunctional devices, which allow the diagnosis and treatment of devastating diseases. Over the past few decades, biodegradable polymers have been studied for the fabrication of drug delivery systems. There was extensive development of biodegradable polymeric nanoparticles for drug delivery and tissue engineering, in view of their applications in controlling the release of drugs, stabilizing labile molecules from degradation and site-specific drug targeting. The primary aim is to reduce dosing frequency and prolong the therapeutic outcomes. For this purpose, inert excipients should be selected, being biopolymers, e.g. sodium alginate, commonly used in controlled drug delivery. Nanoparticles composed of alginate (known as anionic polysaccharide widely distributed in the cell walls of brown algae which, when in contact with water, forms a viscous gum) have emerged as one of the most extensively characterized biomaterials used for drug delivery and targeting a set of administration routes. Their advantages include not only the versatile physicochemical properties, which allow chemical modifications for site-specific targeting but also their biocompatibility and biodegradation profiles, as well as mucoadhesiveness. Furthermore, mechanical strength, gelation, and cell affinity can be modulated by combining alginate nanoparticles with other polymers, surface tailoring using specific targeting moieties and by chemical or physical cross-linking. However, for every physicochemical modification in the macromolecule/ nanoparticles, a new toxicological profile may be obtained. In this paper, the different aspects related to the use of alginate nanoparticles for drug delivery and targeting have been revised, as well as how their toxicological profile will determine the therapeutic outcome of the drug delivery system.

Engineered Retroviruses as Fluorescent Biological Reference Particles for Small Particle Flow Cytometry

ABSTRACTThere has been renewed interest in the use of flow cytometry for single particle phenotypic analysis of particles in the nanometer size-range such as viruses, organelles, bacteria and extracellular vesicles (EVs). However, many of these particles are smaller than 200 nm in diameter, which places them at the limit of detection for many commercial flow cytometers. The use of reference particles of diameter, fluorescence, and light-scattering properties akin to those of the small biological particles being studied is therefore imperative for accurate and reproducible data acquisition and reporting across different instruments and analytical technologies. We show here that an engineered murine leukemia virus (MLV) can act as a fluorescence reference particle for other small particles such as retroviruses and EVs. More specifically, we show that engineered MLV is a highly monodisperse enveloped particle that can act as a surrogate to demonstrate the various effects of antibody labeling on the physical properties of small biological particles in a similar diameter range.

Nanocomposites in Controlled & Targeted Drug Delivery Systems

In recent years, development of different types of nanocomposites have increased their utilization in the biomedical and pharmaceutical sciences. The nanometer size range and unique composition make nanocomposites a beneficial alternative to any single conventional material. The present chapter provides a general overview of nanocomposites, discusses different types of nanocomposites such as metal, ceramic and polymer nanocomposites. The discussion is further focused on different nanocomposite based controlled and targeted systems developed for delivery of various drugs including anti-cancer, anti-microbial, anti-inflammatory, anti-diabetic and cardiovascular drugs.

Synthesis of iron oxide nanoparticles in a continuous flow spiral microreactor and Corning® advanced flow™ reactor

In the present work, synthesis of iron oxide nanoparticles (NPs) using continuous flow microreactor (MR) and advanced flow™ reactor (AFR™) has been investigated with evaluation of the efficacy of the two types of MRs. Effect of the different operating parameters on the characteristics of the obtained NPs has also been investigated. The synthesis of iron oxide NPs was based on the co-precipitation and reduction reactions using iron (III) nitrate precursor and sodium hydroxide as reducing agents. The iron oxide NPs were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and X-ray diffraction (XRD) analysis. The mean particle size of the obtained NPs was less than 10 nm at all flow rates (over the range of 20−60 ml/h) in the case of spiral MR, while, in the case of AFR™, the particle size of NPs was below 20 nm with no specific trend observed with the operating flow rates. The XRD and TEM analyses of iron oxide NPs confirmed the crystalline nature and nanometer size range, respectively. Further, magnetic properties of the synthesized iron oxide NPs were studied using electron spin resonance spectroscopy; the resonance absorption peak shows theg-factor values as 2.055 and 2.034 corresponding to the magnetic fields of 319.28 and 322.59 mT for MR and AFR™, respectively.