scholarly journals Use of Protamine in Nanopharmaceuticals—A Review

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1508
Author(s):  
Ivana Ruseska ◽  
Katja Fresacher ◽  
Christina Petschacher ◽  
Andreas Zimmer
Keyword(s):  
Electrostatic Interactions ◽  
Delivery Systems ◽  
Biologically Active ◽  
Active Components ◽  
New Class ◽  
Self Assembling ◽  
Current State ◽  
Phosphate Backbone ◽  
Small Molecule Therapeutics ◽  
Positively Charged

Macromolecular biomolecules are currently dethroning classical small molecule therapeutics because of their improved targeting and delivery properties. Protamine-a small polycationic peptides represent a promising candidate. In nature, it binds and protects DNA against degradation during spermatogenesis due to electrostatic interactions between the negatively charged DNA-phosphate backbone and the positively charged protamine. Researchers are mimicking this technique to develop innovative nanopharmaceutical drug delivery systems, incorporating protamine as a carrier for biologically active components such as DNA or RNA. The first part of this review highlights ongoing investigations in the field of protamine-associated nanotechnology, discussing the self-assembling manufacturing process and nanoparticle engineering. Immune-modulating properties of protamine are those that lead to the second key part, which is protamine in novel vaccine technologies. Protamine-based RNA delivery systems in vaccines (some belong to the new class of mRNA-vaccines) against infectious disease and their use in cancer treatment are reviewed, and we provide an update on the current state of latest developments with protamine as pharmaceutical excipient for vaccines.

scholarly journals Protamine – A Review on an Oligonucleotide-Binding Peptide Applied in Nanopharmaceuticals including Vaccines

2021 ◽  
Author(s):  
Ivana Ruseska ◽  
Katja Alexandra Fresacher ◽  
Christina Petschacher ◽  
Andreas Zimmer
Keyword(s):  
Delivery Systems ◽  
Biologically Active ◽  
Active Components ◽  
New Class ◽  
Self Assembling ◽  
Current State ◽  
Phosphate Backbone ◽  
Polycationic Peptide ◽  
Small Molecule Therapeutics ◽  
Positively Charged

In our modern days, macromolecular biomolecules are dethroning classical small molecule therapeutics because of improved targeting and delivery properties. Protamine – a small polycationic peptide represents such a promising candidate. In nature, it binds and protects DNA against degradation during spermatogenesis due to electrostatic interaction between the negatively charged DNA-Phosphate backbone and the positively charged protamine. Researchers are mimicking this technique in order to develop innovative nanopharmaceutical drug delivery systems, incorporating protamine as carrier for biologically active components such as DNA or RNA. The first key part of this review highlights ongoing investigation in the field of protamine-associated nanotechnology, discussing the self-assembling manufacturing process and nanoparticle engineering. Immune-modulating properties of protamine are referred which lead to the second key part protamine in novel vaccine technologies. Protamine-based RNA delivery systems in vaccines (some of them belong to the new class of mRNA-vaccines) against infectious disease and their use in cancer treatment are reviewed and an update on the current state of latest developments with protamine as pharmaceutical excipient for vaccines is given.

Characteristics of the Interaction between Thrombin Exosite1 and the Sequence 269-297 of Platelet Glycoprotein Ibα

1998 ◽  
Vol 80 (08) ◽  
pp. 310-315 ◽  
Author(s):  
Marie-Christine Bouton ◽  
Christophe Thurieau ◽  
Marie-Claude Guillin ◽  
Martine Jandrot-Perrus
Keyword(s):  
Platelet Activation ◽  
Electrostatic Interactions ◽  
Platelet Glycoprotein ◽  
Thrombin Receptor ◽  
Central Position ◽  
Amidolytic Activity ◽  
N Terminus ◽  
Hydrolysis Of ◽  
Chemical Cross Linking ◽  
Positively Charged

SummaryThe interaction between GPIb and thrombin promotes platelet activation elicited via the hydrolysis of the thrombin receptor and involves structures located on the segment 238-290 within the N-terminal domain of GPIbα and the positively charged exosite 1 on thrombin. We have investigated the ability of peptides derived from the 269-287 sequence of GPIbα to interact with thrombin. Three peptides were synthesized, including Ibα 269-287 and two scrambled peptides R1 and R2 which are comparable to Ibα 269-287 with regards to their content and distribution of anionic residues. However, R2 differs from both Ibα 269-287 and R1 by the shifting of one proline from a central position to the N-terminus. By chemical cross-linking, we observed the formation of a complex between 125I-Ibα 269-287 and α-thrombin that was inhibited by hirudin, the C-terminal peptide of hirudin, sodium pyrophosphate but not by heparin. The complex did not form when γ-thrombin was substituted for α-thrombin. Ibα 269-287 produced only slight changes in thrombin amidolytic activity and inhibited thrombin binding to fibrin. R1 and R2 also formed complexes with α-thrombin, modified slightly its catalytic activity and inhibited its binding to fibrin. Peptides Ibα 269-287 and R1 inhibited platelet aggregation and secretion induced by low thrombin concentrations whereas R2 was without effect. Our results indicate that Ibα 269-287 interacts with thrombin exosite 1 via mainly electrostatic interactions, which explains why the scrambled peptides also interact with exosite 1. Nevertheless, the lack of effect of R2 on thrombin-induced platelet activation suggests that proline 280 is important for thrombin interaction with GPIb.

PRODUCTION OF BLENDED JUICE FROM PUMPKIN, QUINCE, PERSIMMON

2018 ◽  
pp. 59-62
Author(s):  
I. A. Kyazimova ◽  
А. А. Kasumova ◽  
А. А. Nabiev
Keyword(s):  
Phenolic Compounds ◽  
Organic Acids ◽  
New Technology ◽  
Mineral Elements ◽  
Biologically Active ◽  
Active Components ◽  
Aliphatic Acids ◽  
Free Glucose ◽  
Dietary Value ◽  
Quantitative Indicators

Production of plant products, including juices around the world increases continuously. In the fruit and vegetable juices contain a significant amount of monosaccharides (glucose and fructose), organic acids, vitamins, phenolic compounds, mineral substances and other biologically active components that determine the nutritional and dietary value. For the prevention of various diseases associated with impaired metabolic processes, we developed a new technology of preparation of food by blending juice of pumpkin, quince and persimmon. Thus prepared organic blended juice contains a substantial amount of free glucose and fructose, different phenolic compounds, a sufficient amount of organic acids, mineral elements, including iodine and other components that determine its nutritional and biological value. In prepared juices were evaluated the quantitative indicators of β-carotene, vitamin C, glucose and fructose, sucrose, starch, pectin substances. Also in the atomic absorbtion spectrometer Analyst 400 (PerkinElmer, USA) was analyzed content of the organic acids and phenolic compounds. Prepared juices were tested in accordance with 10 point scoring scale. It is established that all juices contain a sufficient amount of the minerals. In pumpkin and quince juices not contain iodine while it presents in sufficient amount in persimmon juice that’s why in the blended juice mineral in addition to mineral elements iodine are contained. In pumpkin and persimmon aliphatic acids are contained in small amount. For this reason during the blending process was used quince juice which is rich in aliphatic acids. The blended juice is light straw color, with delicious flavor, a slight astringent property and a balanced taste.

scholarly journals Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Federica Palombarini ◽  
Silvia Masciarelli ◽  
Alessio Incocciati ◽  
Francesca Liccardo ◽  
Elisa Di Fabio ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Targeted Delivery ◽  
Myeloid Leukemia ◽  
Electrostatic Interactions ◽  
Archaeoglobus Fulgidus ◽  
Leukemia Cells ◽  
Cellular Delivery ◽  
Self Assembling ◽  
Wide Range ◽  
Hybrid Nanoparticle

Abstract Background In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells. Results Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation. Conclusion The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells. Graphic abstract

scholarly journals Highly Osmotic Oxidized Sucrose-Crosslinked Polyethylenimine for Gene Delivery Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 87
Author(s):  
Jaehong Park ◽  
Kyusik Kim ◽  
Sohee Jeong ◽  
Migyeom Lee ◽  
Tae-il Kim
Keyword(s):  
Gene Delivery ◽  
Reductive Amination ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Buffering Capacity ◽  
Serum Stability ◽  
High Osmolality ◽  
Cox 2 ◽  
Serum Free Conditions ◽  
Positively Charged

In this work, highly osmotic oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers were developed for gene delivery systems, and the transfection mechanism is examined. First, periodate-oxidized sucrose and polyethylenimine 2K (PEI2K) were crosslinked with various feed ratios via reductive amination. The synthesis was confirmed by 1H NMR and FTIR. The synthesized SP2K polymers could form positively charged (~40 mV zeta-potential) and nano-sized (150–200 nm) spherical polyplexes with plasmid DNA (pDNA). They showed lower cytotoxicity than PEI25K but concentration-dependent cytotoxicity. Among them, SP2K7 and SP2K10 showed higher transfection efficiency than PEI25K in both serum and serum-free conditions, revealing the good serum stability. It was found that SP2K polymers possessed high osmolality and endosome buffering capacity. The transfection experiments with cellular uptake inhibitors suggest that the transfection of SP2K polymers would progress by multiple pathways, including caveolae-mediated endocytosis. It was also thought that caveolae-mediated endocytosis of SP2K polyplexes would be facilitated through cyclooxygenase-2 (COX-2) expression induced by high osmotic pressure of SP2K polymers. Confocal microscopy results also supported that SP2K polyplexes would be internalized into cells via multiple pathways and escape endosomes efficiently via high osmolality and endosome buffering capacity. These results demonstrate the potential of SP2K polymers for gene delivery systems.

scholarly journals Combining Dextran Conjugates with Stimuli-Responsive and Folate-Targeting Activity: A New Class of Multifunctional Nanoparticles for Cancer Therapy

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1108
Author(s):  
Manuela Curcio ◽  
Alessandro Paolì ◽  
Giuseppe Cirillo ◽  
Sebastiano Di Pietro ◽  
Martina Forestiero ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Drug Release ◽  
Metastatic Cancer ◽  
Stimuli Responsive ◽  
Cancer Disease ◽  
New Class ◽  
Self Assembling ◽  
Redox Responsive ◽  
Potential Applicability ◽  
Mean Size

Nanoparticles with active-targeting and stimuli-responsive behavior are a promising class of engineered materials able to recognize the site of cancer disease, targeting the drug release and limiting side effects in the healthy organs. In this work, new dual pH/redox-responsive nanoparticles with affinity for folate receptors were prepared by the combination of two amphiphilic dextran (DEX) derivatives. DEXFA conjugate was obtained by covalent coupling of the polysaccharide with folic acid (FA), whereas DEXssPEGCOOH derived from a reductive amination step of DEX was followed by condensation with polyethylene glycol 600. After self-assembling, nanoparticles with a mean size of 50 nm, able to be destabilized in acidic pH and reducing media, were obtained. Doxorubicin was loaded during the self-assembling process, and the release experiments showed the ability of the proposed system to modulate the drug release in response to different pH and redox conditions. Finally, the viability and uptake experiments on healthy (MCF-10A) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a new drug vector in cancer therapy.

scholarly journals Hepatoprotective Effect of Mixture of Dipropyl Polysulfides in Concanavalin A-Induced Hepatitis

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 1022
Author(s):  
Dragana Arsenijevic ◽  
Bojana Stojanovic ◽  
Jelena Milovanovic ◽  
Aleksandar Arsenijevic ◽  
Milos Simic ◽  
...  
Keyword(s):  
Concanavalin A ◽  
Messenger Rna ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
Biological Activities ◽  
Biologically Active ◽  
Organosulfur Compounds ◽  
Liver Inflammation ◽  
Regulatory Cells ◽  
Active Components

The main biologically active components of plants belonging to the genus Allium, responsible for their biological activities, including anti-inflammatory, antioxidant and immunomodulatory, are organosulfur compounds. The aim of this study was to synthetize the mixture of dipropyl polysulfides (DPPS) and to test their biological activity in acute hepatitis. C57BL/6 mice were administered orally with DPPS 6 h before intravenous injection of Concanavalin A (ConA). Liver inflammation, necrosis and hepatocytes apoptosis were determined by histological analyses. Cytokines in liver tissue were determined by ELISA, expression of adhesive molecules and enzymes by RT PCR, while liver mononuclear cells were analyzed by flow cytometry. DPPS pretreatment significantly attenuated liver inflammation and injury, as evidenced by biochemical and histopathological observations. In DPPS-pretreated mice, messenger RNA levels of adhesion molecules and NADPH oxidase complex were significantly reduced, while the expression of SOD enzymes was enhanced. DPPS pretreatment decreased protein level of inflammatory cytokines and increased percentage of T regulatory cells in the livers of ConA mice. DPPS showed hepatoprotective effects in ConA-induced hepatitis, characterized by attenuation of inflammation and affection of Th17/Treg balance in favor of T regulatory cells and implicating potential therapeutic usage of DPPS mixture in inflammatory liver diseases.

Biologically active components from mycobacterial cell walls

1975 ◽  
Vol 16 (1) ◽  
pp. 11-24 ◽  
Author(s):  
Thomas J. Meyer ◽  
Edgar Ribi ◽  
Ichiro Azuma
Keyword(s):  
Cell Walls ◽  
Biologically Active ◽  
Active Components ◽  
Mycobacterial Cell

Effects of pollution and climate change on the ecosystem components

2021 ◽  
Author(s):  
Yuriy Lykholat
Keyword(s):  
Endocrine System ◽  
Biologically Active ◽  
Soil Conditions ◽  
Negative Effects ◽  
Current State ◽  
Herbaceous Communities ◽  
Active Chemical ◽  
Study Results ◽  
Ecological Patterns ◽  
The Relationship

The book contains the study results of the environmental and soil conditions of the transformed territories, the ecological patterns of woody plants natural communities’ formation as well as the features of the herbaceous communities’ succession in flooded areas. The current state of forest areas is highlighted, the problems of forest management and their exploitation in Ukraine are outlined. Aspects of anthropogenic impact on natural aquatic ecosystems are shown and various biotesting methods of negative effects are characterized. The relationship between the presence of exogenous biologically active chemical compounds in the environment and damage to the endocrine system of animals has been revealed. The scientific manuscript is intended for ecologists, specialists interested in environmental management and environmental protection. The book may be useful for graduate students and scientific researchers.

Purification and characterization of tuberculin-active components from BCG

1975 ◽  
Vol 21 (12) ◽  
pp. 2019-2027
Author(s):  
M. Laguerre ◽  
R. Turcotte
Keyword(s):  
Physicochemical Properties ◽  
Guinea Pigs ◽  
Gel Filtration ◽  
Biologically Active ◽  
Polyacrylamide Gels ◽  
Active Components ◽  
Purification And Characterization ◽  
Molecular Weights ◽  
Antigenic Activity

The tuberculin activity of protoplasmic extracts isolated from living BCG was purified successively by gel filtration on Sephadex G-100 and G-75, and by electrophoresis on 7.5% and on gradient (6–18%) polyacrylamide gels. The tuberculin-active fractions, as determined in BCG-sensitized guinea pigs, were used as the starting material for each of the following fractionation steps.The physicochemical properties and the antigenic activity of the biologically active fractions have shown that a single component, or only a few ones with similar properties, possessed high tuberculin activity. These active components were proteins having relatively high molecular weights (about 72 000) and could behave as antigens.

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