-
Advanced Static and Dynamic Fluorescence Microscopy Techniques to Investigate Drug Delivery Systems.Pharmaceutics Jun 2021In the past decade(s), fluorescence microscopy and laser scanning confocal microscopy (LSCM) have been widely employed to investigate biological and biomimetic systems... (Review)
Review
In the past decade(s), fluorescence microscopy and laser scanning confocal microscopy (LSCM) have been widely employed to investigate biological and biomimetic systems for pharmaceutical applications, to determine the localization of drugs in tissues or entire organisms or the extent of their cellular uptake (in vitro). However, the diffraction limit of light, which limits the resolution to hundreds of nanometers, has for long time restricted the extent and quality of information and insight achievable through these techniques. The advent of super-resolution microscopic techniques, recognized with the 2014 Nobel prize in Chemistry, revolutionized the field thanks to the possibility to achieve nanometric resolution, i.e., the typical scale length of chemical and biological phenomena. Since then, fluorescence microscopy-related techniques have acquired renewed interest for the scientific community, both from the perspective of instrument/techniques development and from the perspective of the advanced scientific applications. In this contribution we will review the application of these techniques to the field of drug delivery, discussing how the latest advancements of static and dynamic methodologies have tremendously expanded the experimental opportunities for the characterization of drug delivery systems and for the understanding of their behaviour in biologically relevant environments.
PubMed: 34208080
DOI: 10.3390/pharmaceutics13060861 -
Nanoscale Advances Jul 2021Surface plasmons in metals promise many fascinating properties and applications in optics, sensing, photonics and nonlinear fields. Plasmonic nanostructures with... (Review)
Review
Surface plasmons in metals promise many fascinating properties and applications in optics, sensing, photonics and nonlinear fields. Plasmonic nanostructures with extremely small features especially demonstrate amazing new effects as the feature sizes scale down to the sub-nanometer scale, such as quantum size effects, quantum tunneling, spill-out of electrons and nonlocal states The unusual physical, optical and photo-electronic properties observed in metallic structures with extreme feature sizes enable their unique applications in electromagnetic field focusing, spectra enhancing, imaging, quantum photonics, In this review, we focus on the new effects, fabrication and applications of plasmonic metal nanostructures with extremely small features. For simplicity and consistency, we will focus our topic on the plasmonic metal nanostructures with feature sizes of sub-nanometers. Subsequently, we discussed four main and typical plasmonic metal nanostructures with extremely small features, including: (1) ultra-sharp plasmonic metal nanotips; (2) ultra-thin plasmonic metal films; (3) ultra-small plasmonic metal particles and (4) ultra-small plasmonic metal nanogaps. Additionally, the corresponding fascinating new effects (quantum nonlinear, non-locality, quantum size effect and quantum tunneling), applications (spectral enhancement, high-order harmonic wave generation, sensing and terahertz wave detection) and reliable fabrication methods will also be discussed. We end the discussion with a brief summary and outlook of the main challenges and possible breakthroughs in the field. We hope our discussion can inspire the broader design, fabrication and application of plasmonic metal nanostructures with extremely small feature sizes in the future.
PubMed: 36133477
DOI: 10.1039/d1na00237f -
Nanomaterials (Basel, Switzerland) Apr 2022Calcium carbonate (CaCO) particles represent an appealing choice as a drug delivery system due to their biocompatibility, biodegradability, simplicity and...
Calcium carbonate (CaCO) particles represent an appealing choice as a drug delivery system due to their biocompatibility, biodegradability, simplicity and cost-effectiveness of manufacturing, and stimulus-responsiveness. Despite this, the synthesis of CaCO particles with controlled size in the nanometer range via a scalable manufacturing method remains a major challenge. Here, by using a co-precipitation technique, we investigated the impact on the particle size of different synthesis parameters, such as the salt concentration, reaction time, stirring speed, and temperature. Among them, the salt concentration and temperature resulted in having a remarkable effect on the particle size, enabling the preparation of well-dispersed spherical nanoparticles with a size below 200 nm. Upon identification of optimized synthesis conditions, the encapsulation of the antitumoral agent resveratrol into CaCO nanoparticles, without significantly impacting the overall size and morphology, has been successfully achieved.
PubMed: 35564205
DOI: 10.3390/nano12091494 -
Pharmaceutics Dec 2022Most drugs used for the treatment of depression, anxiety and related disorders have low absorption, high metabolism, low brain targeting and/or low water solubility,... (Review)
Review
Nano and Microemulsions for the Treatment of Depressive and Anxiety Disorders: An Efficient Approach to Improve Solubility, Brain Bioavailability and Therapeutic Efficacy.
Most drugs used for the treatment of depression, anxiety and related disorders have low absorption, high metabolism, low brain targeting and/or low water solubility, which can make it hard to formulate them at high strength and can also lead to decreased bioavailability. Incorporating these drugs into nanometric emulsions can solve these issues. Hence, the aim of the present review was to assess the potential of nano and micro emulsions for the delivery of antidepressant and anxiolytic drugs. The results from several studies showed that nanometric emulsions were able to increase drug strength up to 20,270-fold (compared to aqueous solubility). Moreover, in general, the formulations showed droplet size, polydispersity index, zeta potential, viscosity, osmolality, pH, in vitro drug release and ex vivo drug permeation as adequate for the intended effect and administration route. In vivo animal pharmacokinetic experiments showed that nanometric emulsions improved systemic drug bioavailability and/or brain targeting, and in vivo pharmacodynamic studies showed that they had antidepressant and/or anxiolytic effects, also being apparently safe. Hence, the current review provides proof of the potential of nano and microemulsions for improving solubilization and increasing the overall bioavailability of antidepressant and/or anxiolytic drugs, providing evidence of a possible useful strategy for future therapies.
PubMed: 36559318
DOI: 10.3390/pharmaceutics14122825 -
Beilstein Journal of Nanotechnology 2018Following a brief historical summary of the way in which electron beam lithography developed out of the scanning electron microscope, three state-of-the-art... (Review)
Review
Following a brief historical summary of the way in which electron beam lithography developed out of the scanning electron microscope, three state-of-the-art charged-particle beam nanopatterning technologies are considered. All three have been the subject of a recently completed European Union Project entitled "Single Nanometre Manufacturing: Beyond CMOS". Scanning helium ion beam lithography has the advantages of virtually zero proximity effect, nanoscale patterning capability and high sensitivity in combination with a novel fullerene resist based on the sub-nanometre C molecule. The shot noise-limited minimum linewidth achieved to date is 6 nm. The second technology, focused electron induced processing (FEBIP), uses a nozzle-dispensed precursor gas either to etch or to deposit patterns on the nanometre scale without the need for resist. The process has potential for high throughput enhancement using multiple electron beams and a system employing up to 196 beams is under development based on a commercial SEM platform. Among its potential applications is the manufacture of templates for nanoimprint lithography, NIL. This is also a target application for the third and final charged particle technology, viz. field emission electron scanning probe lithography, FE-eSPL. This has been developed out of scanning tunneling microscopy using lower-energy electrons (tens of electronvolts rather than the tens of kiloelectronvolts of the other techniques). It has the considerable advantage of being employed without the need for a vacuum system, in ambient air and is capable of sub-10 nm patterning using either developable resists or a self-developing mode applicable for many polymeric resists, which is preferred. Like FEBIP it is potentially capable of massive parallelization for applications requiring high throughput.
PubMed: 30498657
DOI: 10.3762/bjnano.9.266 -
Nano-micro Letters 2015Antibacterial activity of zinc oxide nanoparticles (ZnO-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to... (Review)
Review
Antibacterial activity of zinc oxide nanoparticles (ZnO-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many microorganisms exist in the range from hundreds of nanometers to tens of micrometers. ZnO-NPs exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size leading to enhanced particle surface reactivity. ZnO is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. This review covered ZnO-NPs antibacterial activity including testing methods, impact of UV illumination, ZnO particle properties (size, concentration, morphology, and defects), particle surface modification, and minimum inhibitory concentration. Particular emphasize was given to bactericidal and bacteriostatic mechanisms with focus on generation of reactive oxygen species (ROS) including hydrogen peroxide (HO), OH (hydroxyl radicals), and O (peroxide). ROS has been a major factor for several mechanisms including cell wall damage due to ZnO-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force and uptake of toxic dissolved zinc ions. These have led to mitochondria weakness, intracellular outflow, and release in gene expression of oxidative stress which caused eventual cell growth inhibition and cell death. In some cases, enhanced antibacterial activity can be attributed to surface defects on ZnO abrasive surface texture. One functional application of the ZnO antibacterial bioactivity was discussed in food packaging industry where ZnO-NPs are used as an antibacterial agent toward foodborne diseases. Proper incorporation of ZnO-NPs into packaging materials can cause interaction with foodborne pathogens, thereby releasing NPs onto food surface where they come in contact with bad bacteria and cause the bacterial death and/or inhibition.
PubMed: 30464967
DOI: 10.1007/s40820-015-0040-x -
Biophysical Journal Oct 2020Biological cells deform on a nanometer scale when their transmembrane voltage changes, an effect that has been visualized during the action potential using quantitative...
Biological cells deform on a nanometer scale when their transmembrane voltage changes, an effect that has been visualized during the action potential using quantitative phase imaging. Similar changes in the optical path length have been observed in photoreceptor outer segments after a flash stimulus via phase-resolved optical coherence tomography. These optoretinograms reveal a fast, millisecond-scale contraction of the outer segments by tens of nanometers, followed by a slow (hundreds of milliseconds) elongation reaching hundreds of nanometers. Ultrafast measurements of the contractile response using line-field phase-resolved optical coherence tomography show a logarithmic increase in amplitude and a decreasing time to peak with increasing stimulus intensity. We present a model that relates the early receptor potential to these deformations based on the voltage-dependent membrane tension-the mechanism observed earlier in neurons and other electrogenic cells. The early receptor potential is caused by conformational changes in opsins after photoisomerization, resulting in the fractional shift of the charge across the disk membrane. Lateral repulsion of the ions on both sides of the membrane affects its surface tension and leads to its lateral expansion. Because the volume of the disks does not change on a millisecond timescale, their lateral expansion leads to an axial contraction of the outer segment. With increasing stimulus intensity and the resulting tension, the area expansion coefficient of the disk membrane also increases as thermally induced fluctuations are pulled flat, resisting further expansion. This leads to the logarithmic saturation observed in measurements as well as the peak shift in time. This imaging technique therefore relates the structural changes in the photoreceptor to the underlying neurological function of transducing light into electrical signals. Such label-free optical monitoring of neural activity using fast interferometry may be applicable not only to optoretinography but also to neuroscience in general.
Topics: Action Potentials; Interferometry; Ions; Neurons; Photoreceptor Cells
PubMed: 33031739
DOI: 10.1016/j.bpj.2020.09.005 -
Biomicrofluidics Jan 2019The resistive pulse method based on measuring the ion current trace as a biomolecule passing through a nanopore has become an important tool in biotechnology for...
The resistive pulse method based on measuring the ion current trace as a biomolecule passing through a nanopore has become an important tool in biotechnology for characterizing molecules. A detailed physical understanding of the translocation process is essential if one is to extract the relevant molecular properties from the current signal. In this Perspective, we review some recent progress in our understanding of hydrodynamic flow and transport through nanometer sized pores. We assume that the problems of interest can be addressed through the use of the continuum version of the equations of hydrodynamic and ion transport. Thus, our discussion is restricted to pores of diameter greater than about ten nanometers: such pores are usually synthetic. We address the fundamental nanopore hydrodynamics and ion transport mechanisms and review the wealth of observed phenomena due to these mechanisms. We also suggest future ionic circuits that can be synthesized from different ionic modules based on these phenomena and their applications.
PubMed: 30867871
DOI: 10.1063/1.5083913 -
Iranian Journal of Pharmaceutical... 2010
PubMed: 24381596
DOI: No ID Found -
Nature Communications May 2023The spatial organization of cell membrane glycoproteins and glycolipids is critical for mediating the binding of ligands, receptors, and macromolecules on the plasma...
The spatial organization of cell membrane glycoproteins and glycolipids is critical for mediating the binding of ligands, receptors, and macromolecules on the plasma membrane. However, we currently do not have the methods to quantify the spatial heterogeneities of macromolecular crowding on live cell surfaces. In this work, we combine experiment and simulation to report crowding heterogeneities on reconstituted membranes and live cell membranes with nanometer spatial resolution. By quantifying the effective binding affinity of IgG monoclonal antibodies to engineered antigen sensors, we discover sharp gradients in crowding within a few nanometers of the crowded membrane surface. Our measurements on human cancer cells support the hypothesis that raft-like membrane domains exclude bulky membrane proteins and glycoproteins. Our facile and high-throughput method to quantify spatial crowding heterogeneities on live cell membranes may facilitate monoclonal antibody design and provide a mechanistic understanding of plasma membrane biophysical organization.
Topics: Humans; Cell Membrane; Membrane Proteins; Phagocytosis; Antibodies, Monoclonal; Glycoproteins; Macromolecular Substances
PubMed: 37208326
DOI: 10.1038/s41467-023-38525-2