Lymphatic Uptake of Liposomes after Intraperitoneal Administration Primarily Occurs via the Diaphragmatic Lymphatics and is Dependent on Liposome Surface Properties.

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Show simple item record Lee, Given en Han, Sifei en Inocencio, Iasmin en Cao, Enyuan en Hong, Jiwon en Phillips, Anthony en Windsor, John en Porter, Christopher JH en Trevaskis, Natalie L en 2020-01-12T22:19:24Z en 2019-12 en
dc.identifier.issn 1543-8384 en
dc.identifier.uri en
dc.description.abstract Drugs are commonly administered via the intraperitoneal (IP) route to treat localized infections and cancers in patients and to test drug efficacy and toxicity in preclinical studies. Despite this, there remain large gaps in our understanding of drug absorption routes (lymph vs blood) and pharmacokinetics following IP administration. This is particularly true when drugs are administered in complex delivery systems such as liposomes which are the main marketed formulation for several drugs that are administered intraperitoneally. This study investigated the impact of liposome surface properties (charge and PEGylation) on absorption into lymph and blood, and lymphatic disposition patterns, following IP administration. To achieve this, stable 3H-dipalmitoyl-phosphatidylcholine (DPPC) and 14C-sucrose-radiolabeled liposomes of 100-150 nm diameter with negative, neutral, or positive surface charge, or a PEGylated surface, were prepared and administered intraperitoneally to rats. Radiolabel concentrations were measured in lymph, blood, and lymph nodes (LNs). Lymph was collected from the thoracic lymph duct at either the abdomen (ABD) or the jugular-subclavian junction (JSJ). The lymphatic recovery of the radiolabels was substantially lower after administration in positively charged compared to the neutral, negative, or PEGylated liposomes. Radiolabel recovery was substantially greater (up to 18-fold) in the thoracic lymph collected at the JSJ when compared to that at the ABD, suggesting that liposomes entered the lymphatics at the diaphragm. Consistent with this, the concentration of the liposome labels was substantially higher (up to seven-fold) in mediastinal than in mesenteric LNs. Overall, this study shows how the peritoneal absorption and lymphatic disposition of drugs administered intraperitoneally can be manipulated through a careful selection of the drug delivery system and may thus be optimized to treat localized conditions such as cancers, infections, inflammatory diseases, and acute and critical illness. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries Molecular pharmaceutics en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.subject Peritoneum en
dc.subject Lymph Nodes en
dc.subject Animals en
dc.subject Rats en
dc.subject Sucrose en
dc.subject 1,2-Dipalmitoylphosphatidylcholine en
dc.subject Liposomes en
dc.subject Drug Delivery Systems en
dc.subject Injections, Intraperitoneal en
dc.subject Male en
dc.title Lymphatic Uptake of Liposomes after Intraperitoneal Administration Primarily Occurs via the Diaphragmatic Lymphatics and is Dependent on Liposome Surface Properties. en
dc.type Journal Article en
dc.identifier.doi 10.1021/acs.molpharmaceut.9b00855 en
pubs.issue 12 en
pubs.begin-page 4987 en
pubs.volume 16 en
dc.rights.holder Copyright: The author en
pubs.end-page 4999 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype Journal Article en
pubs.elements-id 786480 en Medical and Health Sciences en School of Medicine en Surgery Department en Science en Biological Sciences en Science Research en Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1543-8392 en
pubs.record-created-at-source-date 2019-10-19 en
pubs.dimensions-id 31625752 en

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