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Ultra-high Drug Loading Improves Nanoparticle Efficacy Against Peritoneal Mesothelioma by Robert C. Sabatelle; Rong Liu; Yin P. Hung; Eric Bressler; Eliza J. Neal; Andrew Martin; Iriny Ekladious; Mark W. Grinstaff; Yolonda L. Colson is a Engineering article available to read on EtoBox.

What is Ultra-high Drug Loading Improves Nanoparticle Efficacy Against Peritoneal Mesothelioma about?

Peritoneal mesothelioma is an aggressive disease with a median survival of under three years, due to a lack of effective treatment options. Mesothelioma is traditionally considered a "chemoresistant" tumor; however, low intratumoral drug levels coupled with the inability to administer high systemic doses suggests that therapeutic resistance may be due to poor drug delivery rather than inherent biology. While patient survival may improve with repetitive local intraperitoneal infusions of chemotherapy throughout the perioperative period, these regimens carry associated toxicities and significant peri-operative morbidity. To circumvent these issues, we describe ultra-high drug loaded nanoparticles (NPs) composed of a unique poly(1,2-glycerol carbonate)-graft-succinate-paclitaxel (PGC-PTX + PTX) conjugate. PGC-PTX + PTX NPs are cytotoxic, localize to tumor in vivo, and improve survival in a murine model of human peritoneal mesothelioma after a single intraperitoneal (IP) injection compared to multiple weekly doses of the clinically utilized formulation PTX-C/E. Given their unique pharmacokinetics, a second intraperitoneal dose of PGC-PTX + PTX NPs one month later more than doubles the

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Author

Robert C. Sabatelle; Rong Liu; Yin P. Hung; Eric Bressler; Eliza J. Neal; Andrew Martin; Iriny Ekladious; Mark W. Grinstaff; Yolonda L. Colson

Publisher

Elsevier BV

Published

2022

Language

EN

Field

Engineering (Physical Sciences)