Inducing a change in the pharmacokinetics and biodistribution of poly-l-lysine in rats by complexation with heparin

Johnston, Thomas P.; Kuchimanchi, Kameswara R.; Alur, Hemant; Chittchang, Montakarn; Mitra, Ashim K.

doi:10.1211/0022357021530

Cited by 9 publications

(8 citation statements)

References 31 publications

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“…The major interest in these studies arises from cell biology [5] and from drug delivery investigations [6]. In pharmaceutical applications poly-L-lysines (PLLs) and poly-Larginines (PLAs) serve as model compounds for the distribution of biologically active substances in organisms and different tissues [7]. It was shown that PLLs and PLAs in high concentrations have anticarcinogenic properties [8].…”

Section: Introductionmentioning

confidence: 99%

Poly-l-lysines and poly-l-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane

Reuter

Schwieger

Meister

et al. 2009

Biophysical Chemistry

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. Poly-Llysines and poly-L-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane. Biophysical Chemistry, Elsevier, 2009, 144 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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Section: Introductionmentioning

confidence: 99%

Poly-l-lysines and poly-l-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane

Reuter

Schwieger

Meister

et al. 2009

Biophysical Chemistry

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“…Since intravenously administered polylysine is cleared rapidly from circulation and targets mostly the liver of animals [8,14], we chose an alternative, intraperitoneal route to minimize liver targeting and deliver polylysine to the target organs, such as the brain and spleen, in which prions replicate and accumulate. The accumulation of intraperitoneally delivered polylysine in the brain and spleen was confirmed by ex vivo imaging assays (Ryou, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Toxicological Properties of L-Lysine Polymers in CD-1 Mice

Titlow¹

2013

J. Microbiol. Biotechnol.

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We recently showed that polylysine, the polymer of lysines, retains anti-prion activity. Although the effectiveness of prion inhibition by polylysine was demonstrated with the regimen tolerated in mice, a determination of quantitative polylysine toxicity is necessary to precisely address the in vivo toxicity level of polylysine. In this communication, we report the results of body weight monitoring and hematologic tests performed in CD-1 mice that received two different tolerable dosages of polylysine for an either 5-day or 4-week period. We found that there was no significant alteration in overall serum chemistry, blood cell count, and body weight gain compared with controls. The only notable quantitative change with statistical significance was the decrease of platelet numbers in mice subchronically administered with polylysine. Our results suggest that polylysine is harmless in mice if administered for a short period, but administrations of polylysine in mice may require considerate attention for safety in future investigations as mice chronically receive tolerable doses of polylysine.

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“…Our results indicate that NC-RhB-PEG and PLL-RhB copolymer are eliminated from the bloodstream via hepatobiliary and renal excretion. Renal clearance of PLL-FITC (FITC-labeled poly-L-lysine) was already shown by Johnston et al 25 On the other hand, free RhB remains mainly in the bloodstream and is minimally eliminated from the body by renal clearance. This result concluded that RhB is not released from nanocarriers and is not removed from the body as a degradation product.…”

Section: Dovepressmentioning

confidence: 95%

“…Johnston et al also showed that PLL-FITC accumulates in the liver and spleen, but contrary to our results, they observed the strongest accumulation in the kidney (30 minutes after administration). 25 Our previous research revealed that polyelectrolyte nanocarriers (~100 nm in diameter) were removed from the body during the first spontaneous urination -30 minutes after the injection of nanocarriers. 13 Because in the glomeruli, spaces that enable the filtration of structures are not larger than 5 nm, the observed effect of the rapid removal of the tested nanocarriers with urine seems surprising.…”

Section: Dovepressmentioning

confidence: 99%

Fluorophore Localization Determines the Results of Biodistribution of Core-Shell Nanocarriers

Hinz¹,

Szczęch²,

Szczepanowicz³

et al. 2022

IJN

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Introduction: Biodistribution of nanocarriers with a structure consisting of core and shell is most often analyzed using methods based on labeling subsequent compartments of nanocarriers. This approach may have serious limitations due to the instability of such complex systems under in vivo conditions. Methods: The core-shell polyelectrolyte nanocarriers were intravenously administered to healthy BALB/c mice with breast cancer. Next, biodistribution profiles and elimination routes were determined post mortem based on fluorescence measurements performed for isolated blood, tissue homogenates, collected urine, and feces. Results: Despite the surface PEGylation with PLL-g-PEG, multilayer polyelectrolyte nanocarriers undergo rapid degradation after intravenous administration. This process releases the shell components but not free Rhodamine B. Elements of polyelectrolyte shells are removed by hepatobiliary and renal clearance. Conclusion: Multilayer polyelectrolyte nanocarriers are prone to rapid degradation after intravenous administration. Fluorophore localization determines the obtained results of biodistribution and elimination routes of core-shell nanomaterials. Therefore, precise and reliable analysis of in vivo stability and biodistribution of nanomaterials composed of several compartments requires nanomaterials labeled within each compartment.

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Inducing a change in the pharmacokinetics and biodistribution of poly-l-lysine in rats by complexation with heparin

Cited by 9 publications

References 31 publications

Poly-l-lysines and poly-l-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane

Poly-l-lysines and poly-l-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane

Characterization of Toxicological Properties of L-Lysine Polymers in CD-1 Mice

Fluorophore Localization Determines the Results of Biodistribution of Core-Shell Nanocarriers

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