Design Considerations and Assays for Hemocompatibility of FDA-Approved Nanoparticles

2019 ◽  
Vol 46 (05) ◽  
pp. 637-652
Author(s):  
Amit K. Saha ◽  
Min-Yi S. Zhen ◽  
Folarin Erogbogbo ◽  
Anand K. Ramasubramanian
Keyword(s):  
Biomedical Applications ◽  
Inflammatory Responses ◽  
Mode Of Delivery ◽  
Systemic Circulation ◽  
In Vitro Assays ◽  
Cardiovascular Tissues ◽  
Wide Range ◽  
The Us ◽  
Imaging Sensors

AbstractNanoparticles have numerous biomedical applications including, but not limited to, targeted drug delivery, diagnostic imaging, sensors, and implants for a wide range of diseases including cancer, diabetes, heart disease, and tuberculosis. Although the mode of delivery of the nanoparticles depends on the application and the disease, the nanoparticles are often in immediate contact with the systemic circulation either because of intravenous administration or their ability to enter the bloodstream with relative ease or their longer survival time in circulation. Once in circulation, the nanoparticles may elicit unintended hemostatic and inflammatory responses, and hence the design of nanoparticles for therapeutic applications should take broad hemocompatibility concerns into consideration. In this review, we present the principles underlying the structural and functional design of various classes of nanoparticles that are currently approved by the US Food and Drug Administration, categorize these particles based on their interactions with cardiovascular tissues and ensuing adverse events, and also describe various in vitro assays that may be used evaluate their hemocompatibility.

scholarly journals Bound To Shock: Protection from Lethal Endotoxemic Shock by a Novel, Nontoxic, Alkylpolyamine Lipopolysaccharide Sequestrant

2007 ◽  
Vol 51 (8) ◽  
pp. 2811-2819 ◽  
Author(s):  
Diptesh Sil ◽  
Anurupa Shrestha ◽  
Matthew R. Kimbrell ◽  
Thuan B. Nguyen ◽  
Ashok K. Adisechan ◽  
...  
Keyword(s):  
Polymyxin B ◽  
In Vitro Assays ◽  
Critically Ill Patient ◽  
Peptide Antibiotic ◽  
Outer Membranes ◽  
Wide Range ◽  
Endotoxemic Shock ◽  
Inflammatory Processes ◽  
Shock Protection

ABSTRACT Lipopolysaccharide (LPS), or endotoxin, a structural component of gram-negative bacterial outer membranes, plays a key role in the pathogenesis of septic shock, a syndrome of severe systemic inflammation which leads to multiple-system organ failure. Despite advances in antimicrobial chemotherapy, sepsis continues to be the commonest cause of death in the critically ill patient. This is attributable to the lack of therapeutic options that aim at limiting the exposure to the toxin and the prevention of subsequent downstream inflammatory processes. Polymyxin B (PMB), a peptide antibiotic, is a prototype small molecule that binds and neutralizes LPS toxicity. However, the antibiotic is too toxic for systemic use as an LPS sequestrant. Based on a nuclear magnetic resonance-derived model of polymyxin B-LPS complex, we had earlier identified the pharmacophore necessary for optimal recognition and neutralization of the toxin. Iterative cycles of pharmacophore-based ligand design and evaluation have yielded a synthetically easily accessible N 1,mono-alkyl-mono-homologated spermine derivative, DS-96. We have found that DS-96 binds LPS and neutralizes its toxicity with a potency indistinguishable from that of PMB in a wide range of in vitro assays, affords complete protection in a murine model of LPS-induced lethality, and is apparently nontoxic in vertebrate animal models.

A Review on Application of Novel Solid Nanostructures in Drug Delivery

2018 ◽  
Vol 53 ◽  
pp. 22-36 ◽  
Author(s):  
Habibollah Faraji ◽  
Reza Nedaeinia ◽  
Esmaeil Nourmohammadi ◽  
Bizan Malaekeh-Nikouei ◽  
Hamid Reza Sadeghnia ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Therapy ◽  
Biomedical Applications ◽  
Imaging Biomarkers ◽  
Cellular Functions ◽  
Scientific Innovation ◽  
Wide Range ◽  
Targeted Drug

Nanotechnology as a multidisciplinary and scientific innovation plays an important role in numerous biomedical applications, such as molecular imaging, biomarkers and biosensors and also drug delivery. A wide range of studies have been conducted on using of nanoparticles for early diagnosis and targeted drug therapy of various diseases. In fact, the small size, customized surface, upgraded solubility, or multi-functionality of nanoparticles enabled them to interact with complex cellular functions in new ways which opened many doors and created new biomedical applications. These studies demonstrated that nanotechnology vehicles can formulate biological products effectively, and this nano-formulated products with a potent ability against different diseases, were represented to have better biocompatibility, bioaccessibility and efficacy, under in vitro and in vivo conditions.

scholarly journals HIF-1α is a key mediator of the lung inflammatory potential of lithium-ion battery particles

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Violaine Sironval ◽  
Mihaly Palmai-Pallag ◽  
Rita Vanbever ◽  
François Huaux ◽  
Jorge Mejia ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Hypoxia Inducible Factor ◽  
Lithium Ion ◽  
In Vitro Assays ◽  
Inhalation Toxicity ◽  
Cobalt Nickel ◽  
Occupational Settings

Abstract Background Li-ion batteries (LIB) are increasingly used worldwide. They are made of low solubility micrometric particles, implying a potential for inhalation toxicity in occupational settings and possibly for consumers. LiCoO2 (LCO), one of the most used cathode material, induces inflammatory and fibrotic lung responses in mice. LCO also stabilizes hypoxia-inducible factor (HIF) -1α, a factor implicated in inflammation, fibrosis and carcinogenicity. Here, we investigated the role of cobalt, nickel and HIF-1α as determinants of toxicity, and evaluated their predictive value for the lung toxicity of LIB particles in in vitro assays. Results By testing a set of 5 selected LIB particles (LCO, LiNiMnCoO2, LiNiCoAlO2) with different cobalt and nickel contents, we found a positive correlation between their in vivo lung inflammatory activity, and (i) Co and Ni particle content and their bioaccessibility and (ii) the stabilization of HIF-1α in the lung. Inhibition of HIF-1α with chetomin or PX-478 blunted the lung inflammatory response to LCO in mice. In IL-1β deficient mice, HIF-1α was the upstream signal of the inflammatory lung response to LCO. In vitro, the level of HIF-1α stabilization induced by LIB particles in BEAS-2B cells correlated with the intensity of lung inflammation induced by the same particles in vivo. Conclusions We conclude that HIF-1α, stabilized in lung cells by released Co and Ni ions, is a mechanism-based biomarker of lung inflammatory responses induced by LIB particles containing Co/Ni. Documenting the Co/Ni content of LIB particles, their bioaccessibility and their capacity to stabilize HIF-1α in vitro can be used to predict the lung inflammatory potential of LIB particles.

In Vitro Examination of Poly(glycerol sebacate) Degradation Kinetics: Effects of Porosity and Cure Temperature

2014 ◽  
Vol 1621 ◽  
pp. 87-92 ◽  
Author(s):  
Nadia M. Krook ◽  
Courtney LeBlon ◽  
Sabrina S. Jedlicka
Keyword(s):  
Biomedical Applications ◽  
Degradation Kinetics ◽  
Morphological Changes ◽  
Scanning Calorimetry ◽  
Tissue Engineering Scaffolds ◽  
Degradation Study ◽  
Wide Range ◽  
Thermal Changes ◽  
Cure Temperature

ABSTRACTPoly(glycerol sebacate) (PGS) is a biodegradable and biocompatible elastomer that has been used in a wide range of biomedical applications. While a porous format is common for tissue engineering scaffolds, to allow cell ingrowth, PGS degradation has been primarily studied in a nonporous format. The purpose of this research was to investigate the degradation of porous PGS at three frequently used cure temperatures: 120°C, 140°C, and 165°C. The thermal, chemical, mechanical, and morphological changes were examined using thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, compression testing, and scanning electron microscopy. Over the course of the 16-week degradation study, the samples’ pores collapsed. The specimens cured at 120°C demonstrated the most degradation and became gel-like after 16 weeks. Thermal changes were most evident in the 120°C and 140°C cure PGS specimens, as shifts in the melting and recrystallization temperatures occurred. Porous samples cured at all three temperatures displayed a decrease in compressive modulus after 16 weeks. This in vitro study helped to elucidate the effects of porosity and cure temperature on the biodegradation of PGS and will be valuable for the design of future PGS scaffolds.

scholarly journals Adhesion of Neurons and Glial Cells with Nanocolumnar TiN Films for Brain-Machine Interfaces

2021 ◽  
Vol 22 (16) ◽  
pp. 8588
Author(s):  
Alice Abend ◽  
Chelsie Steele ◽  
Heinz-Georg Jahnke ◽  
Mareike Zink
Keyword(s):  
Glial Cells ◽  
Biomedical Applications ◽  
Electrode Materials ◽  
Detection Sensitivity ◽  
In Vitro Assays ◽  
Electric Signal ◽  
Multielectrode Arrays ◽  
Underlying Substrate

Coupling of cells to biomaterials is a prerequisite for most biomedical applications; e.g., neuroelectrodes can only stimulate brain tissue in vivo if the electric signal is transferred to neurons attached to the electrodes’ surface. Besides, cell survival in vitro also depends on the interaction of cells with the underlying substrate materials; in vitro assays such as multielectrode arrays determine cellular behavior by electrical coupling to the adherent cells. In our study, we investigated the interaction of neurons and glial cells with different electrode materials such as TiN and nanocolumnar TiN surfaces in contrast to gold and ITO substrates. Employing single-cell force spectroscopy, we quantified short-term interaction forces between neuron-like cells (SH-SY5Y cells) and glial cells (U-87 MG cells) for the different materials and contact times. Additionally, results were compared to the spreading dynamics of cells for different culture times as a function of the underlying substrate. The adhesion behavior of glial cells was almost independent of the biomaterial and the maximum growth areas were already seen after one day; however, adhesion dynamics of neurons relied on culture material and time. Neurons spread much better on TiN and nanocolumnar TiN and also formed more neurites after three days in culture. Our designed nanocolumnar TiN offers the possibility for building miniaturized microelectrode arrays for impedance spectroscopy without losing detection sensitivity due to a lowered self-impedance of the electrode. Hence, our results show that this biomaterial promotes adhesion and spreading of neurons and glial cells, which are important for many biomedical applications in vitro and in vivo.

scholarly journals Thymodepressin—Unforeseen Immunosuppressor

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6550
Author(s):  
Vladislav I. Deigin ◽  
Julia E. Vinogradova ◽  
Dmitry L Vinogradov ◽  
Marina S. Krasilshchikova ◽  
Vadim T. Ivanov
Keyword(s):  
Experimental Evidence ◽  
Synthetic Peptide ◽  
Biomedical Applications ◽  
Biological Properties ◽  
Peptide Drug ◽  
Wide Range ◽  
History Of ◽  
Available Information

The paper summarizes the available information concerning the biological properties and biomedical applications of Thymodepressin. This synthetic peptide drug displays pronounced immunoinhibitory activity across a wide range of conditions in vitro and in vivo. The history of its unforeseen discovery is briefly reviewed, and the current as well as potential expansion areas of medicinal practice are outlined. Additional experimental evidence is obtained, demonstrating several potential advantages of Thymodepressin over another actively used immunosuppressor drug, cyclosporin A.

scholarly journals Diurnal variation in the proinflammatory activity of urban fine particulate matter (PM2.5) by in vitro assays

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 596
Author(s):  
Christopher Lovett ◽  
Mafalda Cacciottolo ◽  
Farimah Shirmohammadi ◽  
Amin Haghani ◽  
Todd E. Morgan ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Chemical Composition ◽  
Los Angeles ◽  
Messenger Rna ◽  
Inflammatory Responses ◽  
Photochemical Oxidation ◽  
In Vitro Assays ◽  
Diurnal Changes ◽  
Proinflammatory Activity

Background: Ambient particulate matter (PM) smaller than 2.5 µm in diameter (PM2.5) undergoes diurnal changes in chemical composition due to photochemical oxidation. In this study we examine the relationships between oxidative activity and inflammatory responses associated with these diurnal chemical changes. Because secondary PM contains a higher fraction of oxidized PM species, we hypothesized that PM2.5 collected during afternoon hours would induce a greater inflammatory response than primary, morning PM2.5. Methods: Time-integrated aqueous slurry samples of ambient PM2.5 were collected using a direct aerosol-into-liquid collection system during defined morning and afternoon time periods. PM2.5 samples were collected for 5 weeks in the late summer (August-September) of 2016 at a central Los Angeles site. Morning samples, largely consisting of fresh primary traffic emissions (primary PM), were collected from 6-9am (am-PM2.5), and afternoon samples were collected from 12-4pm (pm-PM2.5), when PM composition is dominated by products of photochemical oxidation (secondary PM). The two diurnally phased PM2.5 slurries (am- and pm-PM2.5) were characterized for chemical composition and BV-2 microglia were assayed in vitro for oxidative and inflammatory gene responses. Results: Contrary to expectations, the am-PM2.5 slurry had more proinflammatory activity than the pm-PM2.5 slurry as revealed by nitric oxide (NO) induction, as well as the upregulation of proinflammatory cytokines IL-1β, IL-6, and CCL2 (MCP-1), as assessed by messenger RNA production. Conclusions: The diurnal differences observed in this study may be in part attributed to the greater content of transition metals and water-insoluble organic carbon (WIOC) of am-PM2.5 (primary PM) vs. pm-PM2.5 (secondary PM), as these two classes of compounds can increase PM2.5 toxicity.

scholarly journals Hyaluronic Acid Nanoparticles as Nanomedicine for Treatment of Inflammatory Diseases

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 931 ◽  
Author(s):  
N.Vijayakameswara Rao ◽  
Jun Gi Rho ◽  
Wooram Um ◽  
Pramod Kumar EK ◽  
Van Quy Nguyen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Hyaluronic Acid ◽  
Biomedical Applications ◽  
Therapeutic Agent ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Biological Functions ◽  
Wide Range ◽  
Diagnostic Agents ◽  
Long Acting

Owing to their unique biological functions, hyaluronic acid (HA) and its derivatives have been explored extensively for biomedical applications such as tissue engineering, drug delivery, and molecular imaging. In particular, self-assembled HA nanoparticles (HA-NPs) have been used widely as target-specific and long-acting nanocarriers for the delivery of a wide range of therapeutic or diagnostic agents. Recently, it has been demonstrated that empty HA-NPs without bearing any therapeutic agent can be used therapeutically for the treatment of inflammatory diseases via modulating inflammatory responses. In this review, we aim to provide an overview of the significant achievements in this field and highlight the potential of HA-NPs for the treatment of inflammatory diseases.

Regulatory Perspective on in Vitro Assays as Predictors of Phototoxicity and Photo Co-Carcinogenicity

1998 ◽  
Vol 17 (5) ◽  
pp. 571-575 ◽  
Author(s):  
Amy L. Ellis
Keyword(s):  
Mammalian Cells ◽  
Hairless Mouse ◽  
In Vitro Assays ◽  
In Vitro Tests ◽  
Drug Products ◽  
Drug Classes ◽  
Wide Range ◽  
Regulatory Perspective

Drugs from a variety of chemical classes used for a wide range of therapeutic indications can be photosensitizers in humans. Several drugs are phototoxic in animal models as well; there are no nonclinical data for many. In vitro tests have been developed as predictors of phototoxicity and although they have been used as screens, none have replaced the in vivo tests done in rodents (usually mice or guinea pigs) since these have been good predictors of clinical phototoxicity. Some phototoxic drug classes are co-carcinogens with ultraviolet radiation (UVA and/or UVB) in hairless mice, specifically psoralens, retinoids, and fluo-roquinolones. Treatment with 8-methoxypsoralen and ultraviolet A radiation for psoriasis is also carcinogenic in humans. It has been suggested that in vitro photogenotoxicity assays using microorganisms or mammalian cells may be predictive of photo co-carcinogenicity. Some attractions of these in vitro assays, compared to the hairless mouse photo co-carcinogenicity assay, are their generally shorter duration and lower cost as well as reducing the number of animals used in research. Currently, personnel at the Food and Drug Administration (FDA) are examining the available data on phototoxicity, photogenotoxicity, and photo co-carcinogenicity to determine how this information can best be used toregulate and label drug products, and considering which assays should be recommended under specific circumstances.

scholarly journals Chemical Synthesis and Hemi-Synthesis of Novel Benzimidazole Derivatives Using Microwave-Assisted Process: Chemical Characterization, Bioactivities and Molecular Docking

2020 ◽  
Vol 3 (1) ◽  
pp. 71
Author(s):  
Asmaâ Sameut ◽  
Sarah Yasmine Zanndouche ◽  
Chaimaa Boumaza ◽  
Chaima Dikes ◽  
Borhane Eddine Cherif Ziani
Keyword(s):  
Molecular Docking ◽  
Reducing Power ◽  
Antimicrobial Activities ◽  
In Vitro Assays ◽  
Synthesis Process ◽  
Benzimidazole Derivatives ◽  
Thiobarbituric Acid Reactive Substance ◽  
E Coli ◽  
Wide Range

Benzimidazole derivatives represent a class of heterocyclic compounds that exhibit a wide range of pharmaceutical properties. The present study aimed to investigate the in-vitro antioxidant and antimicrobial activities of newly synthesized benzimidazole derivatives. Compound 1b (2-(1H-1,3-benzodiazol-2-yl) phenol) was synthesized by reacting o-phenylenediamine (OPA) with chemical salicylaldehyde, while compounds 2b (2-(2-[(1E)-2-phenylethenyl]-1H-1,3-benzodiazole) and 3b (2-[(1E)-2,6-dimethylhepta-1,5-dien-1-yl]-1H-1,3-benzodiazole) were obtained through a hemi-synthesis process of, respectively, the cinnamon (cinnamaldehyde, 90.54%) and lemongrass (cis-citral, 43.9%) essential oils previously characterized by GC/MS. Compounds 4b (2-phenyl-1H-benzimidazole) and 5b (5-(1H-benzimidazol-2-yl)benzene-1,2,3-triol) were synthesized with a click chemistry method by reacting the OPA with benzoic acid and gallic acid directly in ethanol under microwave irradiation (MW) at 400 MHz. The structure/purity of the synthesized compounds was clarified by spectroscopy, ATR-FTIR and NMR 1H. Compounds 1b–5b were screened for their antioxidant activity by using four complementary in-vitro assays: DPPH scavenging activity, ferric ion reducing power, β-carotene bleaching inhibition, and Thiobarbituric Acid Reactive Substance Assay (TBARS) formation inhibition. All the tested compounds showed antioxidant potential, with varying performance. Antimicrobial activity was investigated against American Type Culture Collection (ATCC) strains (three Gram- bacteria: Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa; one Gram+ bacteria: Staphylococcus aureus, and one yeast strain: Candida albicans) through the determination of the Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) by using the microdilution method and rapid colorimetric test of p-iodonitrotetrazolium chloride (INT). Compound 5b exhibited the highest potential, especially against S. aureus (MIC = 0.156 mg·mL−1) followed by S. typhi and C. albicans (MIC = 0.3125 mg·mL−1) and then by E. coli and P. aeruginosa. Compound 1b also showed great potential against S. aureus and C. albicans (MIC ˂ 0.3125 mg·mL−1), followed by E. coli and S. typhi (MIC = 0.3125 mg·mL−1) and P. aeruginosa (MIC = 0.625 mg·mL−1). Further molecular docking was conducted using AutoDock Vina 1.1.2 software on S. aureus thymidylate kinase (TMK) protein to highlight the structure–activity relationship of the potent molecules.

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