Design of abiotic polymer ligand-decorated lipid nanoparticles for effective neutralization of target toxins in the blood

2021 ◽  
Author(s):  
Hiroyuki Koide ◽  
Ikumi Yamauchi ◽  
Yu Hoshino ◽  
Go Yasuno ◽  
Takumi Okamoto ◽  
...  
Keyword(s):  
Blood Circulation ◽  
Lipid Nanoparticles ◽  
Circulation Time ◽  
Highly Effective ◽  
Polymer Ligand

We developed abiotic polymer ligand (PL)-decorated lipid nanoparticles (LNPs) to improve PL mobility, decrease aggregation after capturing the target, and increase the blood circulation time to achieve highly effective toxin neutralization in vivo.

scholarly journals Polysialic Acid Modified Liposomes for Improving Pharmacokinetics and Overcoming Accelerated Blood Clearance Phenomenon

Coatings ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 834
Author(s):  
Xi Han ◽  
Ting Zhang ◽  
Mengyang Liu ◽  
Yanzhi Song ◽  
Xinrong Liu ◽  
...  
Keyword(s):  
Blood Circulation ◽  
Polysialic Acid ◽  
Repeated Administration ◽  
The Body ◽  
Circulation Time ◽  
Blood Clearance ◽  
In Vivo Evaluation ◽  
Accelerated Blood Clearance ◽  
Abc Phenomenon

Poly (ethylene glycol) (PEG) modified nanocarriers are being used widely in the drug delivery system (DDS). However, the “accelerated blood clearance (ABC) phenomenon” was induced upon repeated administration of PEG-modified liposomes, resulting in reduced blood circulation time, and increased accumulation in liver and spleen. To avoid the unexpected phenomenon, polysialic acid (PSA) was selected to modify liposomes. PSA is a natural, highly hydrophilic polysaccharide polymer for which no receptors exists in the body. It is non-immunogenic, biodegradable and endows the conjugated bioactive macromolecule and drugs with increased circulation time in vivo. In the present study, the in vivo evaluation showed that PSA modified liposomes (PSA-Lip) afford extended blood circulation in wistar rats and beagle dogs. Moreover, the ABC phenomenon did not occur and the IgM antibody was not induced after repeated injections of PSA-Lip. These results strongly suggest that PSA modification represents a promising strategy to afford good stealth of the liposomes without evoking the ABC phenomenon.

scholarly journals Balancing Cationic and Hydrophobic Content of PEGylated siRNA Polyplexes Enhances Endosome Escape, Stability, Blood Circulation Time, and Bioactivity in Vivo

ACS Nano ◽  
2013 ◽  
Vol 7 (10) ◽  
pp. 8870-8880 ◽  
Author(s):  
Christopher E. Nelson ◽  
James R. Kintzing ◽  
Ann Hanna ◽  
Joshua M. Shannon ◽  
Mukesh K. Gupta ◽  
...  
Keyword(s):  
Blood Circulation ◽  
Circulation Time ◽  
Endosome Escape

A Study on PELGE Nanoparticles as Controlled Drug Delivery Systems for Intravenous

2005 ◽  
Vol 288-289 ◽  
pp. 163-166 ◽  
Author(s):  
You Rong Duan ◽  
W.S. Liu ◽  
J. Liu ◽  
Z.R. Zhang
Keyword(s):  
Ethylene Glycol ◽  
Blood Circulation ◽  
Controlled Drug Delivery ◽  
Drug Carriers ◽  
Circulation Time ◽  
Poly Ethylene Glycol ◽  
Systemic Blood ◽  
Model Drug ◽  
Poly Ethylene

The objective of this study was to evaluate the in vivo characteristics of poly (ethylene glycol)-poly (lacticacid-co-glycolicacid)-poly (ethylene- glycol) (PELGE) copolymers as drug carriers. In order to test this circulation time, mitoxantrone (DHAQ) was used as a model drug in this study. DHAQ nanoparticles (DHAQ-NP) were prepared, subsequently the DHAQ-NP were evaluated by measuring the drug concentration in plasma after intravenous administration via the tail vein of mice. The circulation time of the DHAQ-NP were tested. The results showed prolonged mitoxantrone (DHAQ) residence in systemic blood circulation.

scholarly journals PEG-OligoRNA Hybridization of mRNA for Developing Sterically Stable Lipid Nanoparticles toward In Vivo Administration

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1303 ◽  
Author(s):  
Shota Kurimoto ◽  
Naoto Yoshinaga ◽  
Kazunori Igarashi ◽  
Yu Matsumoto ◽  
Horacio Cabral ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Blood Circulation ◽  
Lipid Nanoparticles ◽  
Translational Activity ◽  
Rapid Clearance ◽  
High Structural Stability ◽  
Lung Capillaries ◽  
In Vivo Administration ◽  
Biological Milieu

Lipid nanoparticles (LNPs) exhibit high potential as carriers of messenger RNA (mRNA). However, the arduous preparation process of mRNA-loaded LNPs remains a huge obstacle for their widespread clinical application. Herein, we tackled this issue by mRNA PEGylation through hybridization with polyethylene glycol (PEG)-conjugated RNA oligonucleotides (PEG-OligoRNAs). Importantly, mRNA translational activity was preserved even after hybridization of 20 PEG-OligoRNAs per mRNA. The straightforward mixing of the PEGylated mRNA with lipofectamine LTX, a commercial lipid-based carrier, just by pipetting in aqueous solution, allowed the successful preparation of mRNA-loaded LNPs with a diameter below 100 nm, whereas the use of non-PEGylated mRNA provided large aggregates above 100- and 1000-nm. In vivo, LNPs prepared from PEG-OligoRNA-hybridized mRNA exhibited high structural stability in biological milieu, without forming detectable aggregates in mouse blood after intravenous injection. In contrast, LNPs from non-PEGylated mRNA formed several micrometer-sized aggregates in blood, leading to rapid clearance from blood circulation and deposition of the aggregates in lung capillaries. Our strategy of mRNA PEGylation was also versatile to prevent aggregation of another type of mRNA-loaded LNP, DOTAP/Chol liposomes. Together, our approach provides a simple and robust preparation method to LNPs for in vivo application.

scholarly journals A versatile method for the selective core-crosslinking of hyaluronic acid nanogels via ketone-hydrazide chemistry: from chemical characterization to in vivo biodistribution

2018 ◽  
Vol 6 (7) ◽  
pp. 1754-1763 ◽  
Author(s):  
Francielle Pelegrin Garcia ◽  
Marlène Rippe ◽  
Mychelle V. P. Companhoni ◽  
Talitha Fernandes Stefanello ◽  
Benoit Louage ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Blood Circulation ◽  
Chemical Characterization ◽  
Circulation Time ◽  
In Vivo Biodistribution ◽  
Tumor Accumulation

Nanogels show long in vivo blood circulation time and high tumor accumulation.

The effect of zwitterionic surface content on blood circulation time of nanocapsule

2020 ◽  
Vol 35 (3) ◽  
pp. 371-384
Author(s):  
Xing Han ◽  
Sidi Li ◽  
Xueping Li ◽  
Qi Zhan ◽  
Yueying Zhan ◽  
...  
Keyword(s):  
Protein Adsorption ◽  
Blood Circulation ◽  
Circulation Time ◽  
H Nmr ◽  
Surface Filling ◽  
Optimal Surface ◽  
Delivery Platform ◽  
Surface Content ◽  
The Relationship

Zwitterionic modification can prolong the blood circulation time of nanocarrier in vivo, but zwitterionic content will affect the functions of nanocarrier such as enzyme-responsive and intracellular or extracellular delivery. Therefore, it is necessary to explore the relationship between the zwitterionic content and circulation time of nanocarrier so as to figure out what content of zwitterion can enable the nanocarrier to obtain both the long blood circulation ability and other functions mentioned above. Herein, using nanocapsule as a research model, we investigated the nanocapsule modified with zwitterion of phosphorylcholine (PC) or carboxybetaine (CB) respectively, and through 1H-NMR quantification we determined the zwitterionic surface content, so as to study the effect of PC or CB surface content on blood circulation performance of nanocapsule. In vivo study showed that the nanocapsule possessed an optimal surface filling ratios range for blood circulation of 43–68% for PC and of 20–68% for CB, with the longest t1/2=37.35 h for PC-nanocapsule and t1/2=45.27 h for CB-nanocapsule. Furthermore, the protein adsorption and macrophage endocytosis experiments indicated that when the surface filling ratio reached 43% for PC-nanocapsule and 20% for CB-nanocapsule, it could effectively reduce the protein adsorption and weaken macrophage endocytosis, thus explaining the phenomenon of long circulation time of nanocapsules from the point of protein adsorption and interaction with immune cells. This study proposes a new direction for designing long-circulating nanocarrier, and provides basis for constructing enzyme-responsive and intracellular or extracellular delivery platform.

scholarly journals Extended in vivo blood circulation time of fluorinated liposomes

FEBS Letters ◽  
1993 ◽  
Vol 336 (3) ◽  
pp. 481-484 ◽  
Author(s):  
Catherine Santaella ◽  
Frédéric Frézard ◽  
Pierre Vierling ◽  
Jean G. Riess
Keyword(s):  
Blood Circulation ◽  
Circulation Time

Fabrication of RGD-conjugated Gd(OH)3:Eu nanorods with enhancement of magnetic resonance, luminescence imaging and in vivo tumor targeting

2016 ◽  
Vol 45 (36) ◽  
pp. 14063-14070 ◽  
Author(s):  
Bianyun Cai ◽  
Zhongbing Huang ◽  
Zhi Wu ◽  
Lei Wang ◽  
Guangfu Yin ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Hydrothermal Method ◽  
Blood Circulation ◽  
Tumor Targeting ◽  
Circulation Time ◽  
Luminescence Imaging

RGD-linked Gd(OH)3:Eu NRs with long blood circulation time were fabricated via a hydrothermal method, PEGylation and thiolation conjugation, and these NRs could enhance in vivo MR and luminescence imagings of gliomas by a good targeting of gliomas.

Pharmacokinetic Evaluation of 99mTc-radiolabeled Solid Lipid Nanoparticles and Chitosan Coated Solid Lipid Nanoparticles

2020 ◽  
Vol 20 (13) ◽  
pp. 1044-1052
Author(s):  
Nasrin Abbasi Gharibkandi ◽  
Sajjad Molavipordanjani ◽  
Jafar Akbari ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Lipid Nanoparticles ◽  
High Resistivity ◽  
Scanning Calorimetry ◽  
Liver Uptake ◽  
Solid Lipid ◽  
Transmission Electron ◽  
Main Portion ◽  
Pharmacokinetic Behavior

Background: Solid Lipid Nanoparticles (SLNs) possess unique in vivo features such as high resistivity, bioavailability, and habitation at the target site. Coating nanoparticles with polymers such as chitosan greatly affects their pharmacokinetic behavior, stability, tissue uptake, and controlled drug delivery. The aim of this study was to prepare and evaluate the biodistribution of 99mTc-labeled SLNs and chitosan modified SLNs in mice. Methods: 99mTc-oxine was prepared and utilized to radiolabel pre-papered SLNs or chitosan coated SLNs. After purification of radiolabeled SLNs (99mTc-SLNs) and radiolabeled chitosan-coated SLNs (99mTc-Chi-SLNs) using Amicon filter, they were injected into BALB/c mice to evaluate their biodistribution patterns. In addition, nanoparticles were characterized using Transmission Electron Microscopy (TEM), Fourier-transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRD) and Dynamic Light Scattering (DLS). Results: 99mTc-oxine with high radiochemical purity (RCP~100%) and stability (RCP > 97% at 24 h) was used to provide 99mTc-SLNs and 99mTc-Chi-SLNs with high initial RCP (100%). TEM image and DLS data suggest 99mTc- SLNs susceptibility to aggregation. To that end, the main portion of 99mTc-SLNs radioactivity accumulates in the liver and intestines, while 99mTc-Chi-SLNs sequesters in the liver, intestines and kidneys. The blood radioactivity of 99mTc-Chi-SLNs was higher than that of 99mTc-SLNs by 7.5, 3.17 and 3.5 folds at 1, 4 and 8 h post-injection. 99mTc- Chi-SLNs uptake in the kidneys in comparison with 99mTc-SLNs was higher by 37.48, 5.84 and 11 folds at 1, 4 and 8h. Conclusion: The chitosan layer on the surface of 99mTc-Chi-SLNs reduces lipophilicity in comparison with 99mTc- SLNs. Therefore, 99mTc-Chi-SLNs are less susceptible to aggregation, which leads to their lower liver uptake and higher kidney uptake and blood concentration.

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