scholarly journals An analytical approach for quantifying the influence of nanoparticle polydispersity on cellular delivered dose

2018 ◽  
Vol 15 (144) ◽  
pp. 20180364 ◽  
Author(s):  
Stuart T. Johnston ◽  
Matthew Faria ◽  
Edmund J. Crampin

Nanoparticles provide a promising approach for the targeted delivery of therapeutic, diagnostic and imaging agents in the body. However, it is not yet fully understood how the physico-chemical properties of the nanoparticles influence cellular association and uptake. Cellular association experiments are routinely performed in an effort to determine how nanoparticle properties impact the rate of nanoparticle–cell association. To compare experiments in a meaningful manner, the association data must be normalized by the amount of nanoparticles that arrive at the cells, a measure referred to as the delivered dose. The delivered dose is calculated from a model of nanoparticle transport through fluid. A standard assumption is that all nanoparticles within the population are monodisperse, namely the nanoparticles have the same physico-chemical properties. We present a semi-analytic solution to a modified model of nanoparticle transport that allows for the nanoparticle population to be polydisperse. This solution allows us to efficiently analyse the influence of polydispersity on the delivered dose. Combining characterization data obtained from a range of commonly used nanoparticles and our model, we find that the delivered dose changes by more than a factor of 2 if realistic amounts of polydispersity are considered.

2011 ◽  
Vol 6 (4) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Erminio Murano ◽  
Danilo Perin ◽  
Riaz Khan ◽  
Massimo Bergamin

Hyaluronan (hyaluronic acid) is a naturally occurring polysaccharide of a linear repeating disaccharide unit consisting of β-(1→4)-linked D-glucopyranuronic acid and β-(1→3)-linked 2-acetamido-2-deoxy-D-glucopyranose, which is present in extracellular matrices, the synovial fluid of joints, and scaffolding that comprises cartilage. In its mechanism of synthesis, its size, and its physico-chemical properties, hyaluronan is unique amongst other glycosaminoglycans. The network-forming, viscoelastic and its charge characteristics are important to many biochemical properties of living tissues. It is an important pericellular and cell surface constituent; its interaction with other macromolecules such as proteins, participates in regulating cell behavior during numerous morphogenic, restorative, and pathological processes in the body. The knowledge of HA in diseases such as various forms of cancers, arthritis and osteoporosis has led to new impetus in research and development in the preparation of biomaterials for surgical implants and drug conjugates for targeted delivery. A concise and focused review on hyaluronan is timely. This review will cover the following important aspects of hyaluronan: (i) biological functions and synthesis in nature; (ii) current industrial production and potential biosynthetic processes of hyaluronan; (iii) chemical modifications of hyaluronan leading to products of commercial significance; and (iv) and the global market position and manufacturers of hyaluronan.


2014 ◽  
Vol 13 (1) ◽  
pp. 135-144
Author(s):  
I. V. Mitrofanova ◽  
I. V. Milto ◽  
I. V. Suhodolo ◽  
G. Yu. Vasyukov

Nanomaterials  –  materials,  whouse  structure  elements  has  proportions  doesn’t  exceed  100  nm.  In superdispersed state matter acquire new properties. In the last decade, carbon nanotubes become the most popular nanomaterials, that cause attention of representatives of various scientific field. The сarbon nanotubes offer new opportunities for biological and medical applications: imaging at the molecular, cellular and tissue levels, biosensors and electrodes based on carbon nanotubes, target delivery of various substances, radiation and photothermal therapy. The most promising of carbon nanotubes in the context of biomedical applications is their ability to penetrate the various tissues of the body and carry large doses of agents, providing diagnostic and therapeutic effects. Functionalized nanotubes are biodegradable. Other current direction of using carbon nanotubes in medicine and biology is to visualize objects on the molecular, cellular and tissue level. Associated with carbon nanotubes contrasting substances improve the visualization of cells and tissues, which can detected new patterns of development of the pathological process. Due to the vagueness of the question of biocompatibility and cytotoxicity of carbon nanotubes possibility of their practical application is hampered. Before the introduction of carbon nanotubes into practical health care is necessary to provide all the possible consequences of using nanotubes. High rates of properties and development of new nanostructures based on carbon nanotubes in the near future will lead to new advances related to the application and development of new parameters that will determine their properties and effects. In these review attention is paid to the structure, physico-chemical properties of nanotubes, their functionalization, pharmacokinetics and pharmacodynamics and all aspects of using of carbon nanotubes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam Čepa ◽  
Veronika Dejmková ◽  
Ladislav Lešetický ◽  
Ivan Jelínek ◽  
Stanislav Smrček ◽  
...  

AbstractUnconjugated bilirubin (UCB) is the end-product of heme catabolism in the intravascular compartment. Although beneficial for human health when mildly elevated in the body, when present at greater than a critical threshold concentration, UCB exerts toxic effects that are related to its physico-chemical properties, particularly affecting the central nervous system. The aim of the present study was to characterize bilirubin-10-sulfonate (ranarubin), a naturally occurring bile pigment, including determination of its mixed acidity constants (pKa*). Thanks to the presence of the sulfonic acid moiety, this compound is more polar compared to UCB, which might theoretically solve the problem with an accurate determination of the UCB pKa* values of its propionic acid carboxylic groups. Bilirubin-10-sulfonate was synthesized by modification of a previously described procedure; and its properties were studied by mass spectrometry (MS), nuclear magnetic resonance (NMR), infrared (IR), and circular dichroism (CD) spectroscopy. Determination of pKa* values of bilirubin-10-sulfonate and UCB was performed by capillary electrophoresis with low pigment concentrations in polar buffers. The identity of the synthesized bilirubin-10-sulfonate was confirmed by MS, and the pigment was further characterized by NMR, IR, and CD spectroscopy. The pKa values of carboxylic acid moieties of bilirubin-10-sulfonate were determined to be 5.02, whereas those of UCB were determined to be 9.01. The physico-chemical properties of bilirubin-10-sulfonate were partially characterized with low pKa* values compared to those of UCB, indicating that bilirubin-10-sulfonate cannot be used as a surrogate pigment for UCB chemical studies. In addition, using a different methodological approach, the pKa* values of UCB were found to be in a mildly alkaline region, confirming the conclusions of a recent critical re-evaluation of this specific issue.


I should like to discuss an approach to the problem of immunological tolerance, which is closely akin to Burnet & Fenner’s (1949) ‘self-marker’ hypothesis, although its emphasis is less on the question of how antibodies are produced than on the detailed fate of potentially antigenic molecules when they leave the plasma and lymph and are catabolized. Dr Cinader’s figures certainly suggest that in tolerant rabbits heterologous albumin is eliminated from the plasma at rates which are substantially identical with those of homologous albumin. This is true also of heterologous plasma proteins in normal rabbits during the period before antibodies appear. Furthermore, we have found that in normal rats, in which albumin and globulin are eliminated at markedly different rates (Campbell, Cuthbertson, Matthews & McFarlane 1956), heterologous albumin behaves much like rat albumin and heterologous γ -globulin like rat γ -globulin for a week or more. It is a reasonable working hypothesis that foreign materials in the circulation are in the first place removed from the tissue fluids by the same mechanisms as deal with native materials possessing similar physico-chemical properties (e.g. molecular weight, surface charge). We are largely ignorant of what these mechanisms might be, except for the part played by reticulo-endothelial cells in removing particulate matter and denatured or aggregated proteins. However, the use by Coons, Leduc & Kaplan (1951) of fluorescent antibody to locate antigenic material in histological sections has shown that apparently undenatured proteins (e.g. bovine albumin, human γ -globulin) introduced into the plasma are detectable in immunologically active form within a wide variety of cells, such as renal tubule cells, liver parenchyma or vascular endothelium, in addition to cells of the reticuloendothelial system proper. There are possibly at least two processes going on concurrently: first, a non-selective ingestion of their surrounding fluid (with all that it contains) by cells which are widely distributed in the body, and are not necessarily confined to the reticulo-endothelial system. The mechanism may well be one of vacuolar ingestion (‘pinocytosis’), for which there is some circumstantial evidence, but which also presents difficulties. This would be one mechanism responsible for normal plasma protein catabolism. Secondly, there may be a selective removal of particulate or aggregated material, especially when negatively charged, by cells of the reticulo-endothelial system, notably by liver Küpffer cells.


Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 634 ◽  
Author(s):  
Marziyeh Ajdary ◽  
Mohammad Moosavi ◽  
Marveh Rahmati ◽  
Mojtaba Falahati ◽  
Mohammad Mahboubi ◽  
...  

Nanoparticles (NPs) are currently used in diagnosis and treatment of many human diseases, including autoimmune diseases and cancer. However, cytotoxic effects of NPs on normal cells and living organs is a severe limiting factor that hinders their use in clinic. In addition, diversity of NPs and their physico-chemical properties, including particle size, shape, surface area, dispersity and protein corona effects are considered as key factors that have a crucial impact on their safe or toxicological behaviors. Current studies on toxic effects of NPs are aimed to identify the targets and mechanisms of their side effects, with a focus on elucidating the patterns of NP transport, accumulation, degradation, and elimination, in both in vitro and in vitro models. NPs can enter the body through inhalation, skin and digestive routes. Consequently, there is a need for reliable information about effects of NPs on various organs in order to reveal their efficacy and impact on health. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1954
Author(s):  
Elena V. Uspenskaya ◽  
Anton V. Syroeshkin ◽  
Tatiana V. Pleteneva ◽  
Ilaha V. Kazimova ◽  
Tatiana V. Grebennikova ◽  
...  

Natural polyelectrolytes, including in the form of complexes with colloidal particles, are increasingly used in pharmacy due to the possibility of regulated attachment of medicinal substances and their targeted delivery to the target organ. However, the formation, stability, and molecular-mass characteristics of polyelectrolyte nanodispersions (ND) vary depending on the nature and composition of the medium of their origin. This is due to the lack of standardized approaches to quality control and regulatory documentation for most natural ND. In this paper, we first introduced the isolation, followed by investigations into their physico-chemical properties and bioactivity. Using the dried droplet method, we were able to detect the “coffee ring effect”. Fractographic studies of the surface structure of EHA and FA dried samples using SEM showed its heterogeneity and the presence of submicron particles encapsulated in the internal molecular cavities of polyelectrolyte. FTIR spectroscopy revealed the ND chemical structure of benzo-α-pyron and benzo-γ-pyron, consisting of nanoparticles and a branched frame part. The main elements detected by X-ray fluorescence in humic substance extract and fulvic acid include Si, P, S, K, Ca, Mn, Fe, Cu, Zn, whereas Fe is in high concentrations. The UV-spectra and fluorescent radiation demonstrated the possibility of studying the effect of the fulvate chromone structure on its optical properties. It is shown that dilution of the initial solutions of polyelectrolytes 1:10 contributes to the detection of smaller nanoparticles and an increase in the absolute value of the negative ζ-potential as a factor of ND stability. A study of the EHS effect on the SARS-CoV-2 virus infectious titer in the Vero E6 cell showed the effective against virus both in the virucidal scheme (the SI is 11.90–22.43) and treatment/prevention scheme (the SI is 34.85–57.33). We assume that polyelectrolyte ND prevent the binding of the coronavirus spike glycoprotein to the receptor. Taking into account the results obtained, we expect that the developed approach can become unified for the standardization of the ND natural polyelectrolytes complex, which has great prospects for use in pharmacy and medicine as a drug with antiviral activity.


1938 ◽  
Vol 38 (3) ◽  
pp. 273-278 ◽  
Author(s):  
R. Th. Scholtens

In an article (Scholtens, 1937) published elsewhere, I have shown that the external smooth properties of typhoid bacilli (stability in physiological salt solution and colony form) depend on the body antigens, not only on the O antigen but also on the Vi antigen.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3253
Author(s):  
Kinga Kazimierska ◽  
Urszula Kalinowska-Lis

Milk and colostrum have high biological potential, and due to their natural origin and non-toxicity, they have many uses in cosmetics and dermatology. Research is ongoing on their potential application in other fields of medicine, but there are still few results; most of the published ones are included in this review. These natural products are especially rich in proteins, such as casein, β-lactoglobulin, α-lactalbumin, lactoferrin, immunoglobulins, lactoperoxidase, lysozyme, and growth factors, and possess various antibacterial, antifungal, antiviral, anticancer, antioxidant, immunomodulatory properties, etc. This review describes the physico-chemical properties of milk and colostrum proteins and the natural functions they perform in the body and compares their composition between animal species (cows, goats, and sheep). The milk- and colostrum-based products can be used in dietary supplementation and for performing immunomodulatory functions; they can enhance the effects of certain drugs and can have a lethal effect on pathogenic microorganisms. Milk products are widely used in the treatment of dermatological diseases for promoting the healing of chronic wounds, hastening tissue regeneration, and the treatment of acne vulgaris or plaque psoriasis. They are also increasingly regarded as active ingredients that can improve the condition of the skin by reducing the number of acne lesions and blackheads, regulating sebum secretion, ameliorating inflammatory changes as well as bestowing a range of moisturizing, protective, toning, smoothing, anti-irritation, whitening, soothing, and antiaging effects.


1960 ◽  
Vol s3-101 (54) ◽  
pp. 133-148
Author(s):  
M. E. CLARK ◽  
R. B. CLARK

A unique ligamentary system occurs in the polychaete Nephtys. Its fine structure and physico-chemical properties have been investigated. The ligaments consist of alternating bands of elastic and inelastic elements, and they attach to the body by means of crystalloid attachment nodes. The nodes are probably glycoprotein in nature as they contain both protein and polysaccharide. They are not birefringent, and they are insoluble in comparison with the other components of the ligaments. Their structural stability is due mainly to strong ionic and hydrogen bonding. They resist enzymatic digestion. The inelastic elements are bundles of thin, birefringent fibrils, 10 to 14 µ in length. The birefringence is positive with respect to the long axis of the fibrils and is primarily intrinsic in nature. The estimated coefficient of birefringence has a value between 10 and 20 x 10-3. The fibrils consist of a protein with an isoelectric point near pH 6.3. The visible structure of the fibrils is due to both hydrogen and ionic bonding, while the birefringence is more dependent on hydrogen bonding. The fibrils resist heating and peptic digestion, but are slowly digested by trypsin. Of all the fibrous proteins, they most resemble collagen. The elastic elements are extremely fine, granular cross-membranes bearing delicate filaments to which the ends of the fibrils are attached. They are continuous with a bounding membrane surrounding the ligament, which also bears granules and is also elastic. Some of the granules appear to be folds of the membrane itself. The membranes consist of a protein which is quickly digested by trypsin but not digested by pepsin. Its isoelectric point lies near pH 5. Hydrogen bonding is more important than ionic bonding in the membranes, and Van der Waals forces may also contribute. Classification of this protein is not yet possible.


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