@inproceedings{7f3ea4450d7f451baf3476cba3202f78,
title = "Sn2 lipase labile prodrugs and contact-facilitated drug delivery for lipid-encapsulated nanomedicines",
abstract = "The concept of achieving Paul Erhlich's inspired vision of a {"}magic bullet{"} to treat disease is now materializing with select monoclonal antibody therapies, but this achievement is not well replicated by current nanomedicine clinical candidates. Nanomedicine technologies have often proven unstable in vivo due to premature release of drug cargoes during circulation resulting in low therapeutic delivery to targeted cells. Compounding this nanoparticle payloads that reach target cells are typically internalized within endosomes, contributing to further drug loss and diminished intracellular drug bioavailability. Historically, size limited extravasation of nanoparticles beyond the circulation followed by inhomogeneous and inadequate deep penetration into disease sites has been the major nanoparticle biological barrier. However, nanomedicines can function as excipients and prolonged release systems to favorably alter drug pharmacokinetics and volume of distributions for greater efficacy and lower toxicity. Sn2 phospholipid prodrugs in conjunction with a contact-facilitated drug delivery mechanism have been found to minimize premature drug diffusional loss during circulation and to increase target cell bioavailability. The Sn2 phospholipid prodrug approach has been applied equally well for vascular constrained lipid-encapsulated particles delivering anti-Angiogenic therapies, such as fumagillin or docetaxel, and to micelles penetrating through inflamed endothelium into disseminated cancers, such as in multiple myeloma with anti-cMYC payloads. Innovations like Sn2 phospholipid prodrugs in combination with the contact-facilitated drug delivery mechanism are poised to contribute to the translational success of nanomedicines by increasing efficacy and safety for an array of poorly treated diseases.",
author = "D. Pan and G. Cui and Pham, {C. T.N.} and Tomasson, {M. H.} and Weilbaecher, {K. N.} and Lanza, {G. M.}",
note = "Funding Information: This paper is based on a presentation by Sandra Laursen at the National Diversity Equity Workshop 2015 on April 14, 2015. The study described was supported by the National Science Foundation under award DRL-0723600. Any opinions, findings, conclusions, or recommendations expressed here are those of the researchers, and do not necessarily represent the official views, opinions, or policy of the National Science Foundation. Funding Information: I (Laursen) am originally a chemist, although I haven{\textquoteright}t been working in chemistry for the last several years. Our research team studies science education and career paths in an independent research unit at the University of Colorado Boulder. The analysis discussed here was a part of a larger study funded by the National Science Foundation (NSF) about the professional preparation of Ph.D. chemists. We were interested in how chemistry departments were responding to calls, over the last two decades or more, for reform of graduate education, especially in preparing students for a wider range of 21st century careers. Our team was interested in how departments were or were not responding to these calls, and to the issues they identified—and in what students were or were not experiencing for career preparation. I summarize here just one part of that work (1). Publisher Copyright: {\textcopyright} 2018 American Chemical Society. All rights reserved.",
year = "2017",
doi = "10.1021/bk-2017-1271.ch008",
language = "English (US)",
isbn = "9780841232747",
series = "ACS Symposium Series",
publisher = "American Chemical Society",
pages = "189--209",
editor = "Ilies, {Marc A.}",
booktitle = "Control of Amphiphile Self-Assembling at the Molecular Level",
address = "United States",
}
