Targeted In Vivo Loading of Red Blood Cells Markedly Prolongs Nanocarrier Circulation.

Autor:	Glassman PM; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States., Villa CH; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.; Department of Pathology & Laboratory Medicine, Division of Transfusion Medicine & Therapeutic Pathology, Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States., Marcos-Contreras OA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States., Hood ED; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States., Walsh LR; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States., Greineder CF; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States., Myerson JW; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States., Shuvaeva T; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States., Puentes L; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States., Brenner JS; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States., Siegel DL; Department of Pathology & Laboratory Medicine, Division of Transfusion Medicine & Therapeutic Pathology, Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States., Muzykantov VR; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Jazyk:	angličtina
Zdroj:	Bioconjugate chemistry [Bioconjug Chem] 2022 Jul 20; Vol. 33 (7), pp. 1286-1294. Date of Electronic Publication: 2022 Jun 16.
DOI:	10.1021/acs.bioconjchem.2c00196
Abstrakt:	Engineering drug delivery systems for prolonged pharmacokinetics (PK) has been an ongoing pursuit for nearly 50 years. The gold standard for PK enhancement is the coating of nanoparticles with polymers, namely polyethylene glycol (PEGylation), which has been applied in several clinically used products. In the present work, we utilize the longest circulating and most abundant component of blood─the erythrocyte─to improve the PK behavior of liposomes. Antibody-mediated coupling of liposomes to erythrocytes was tested in vitro to identify a loading dose that did not adversely impact the carrier cells. Injection of erythrocyte targeting liposomes into mice resulted in a ∼2-fold improvement in the area under the blood concentration versus time profile versus PEGylated liposomes and a redistribution from the plasma into the cellular fraction of blood. These results suggest that in vivo targeting of erythrocytes is a viable strategy to improve liposome PK relative to current, clinically viable strategies.
Databáze:	MEDLINE
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