Table Of Content1
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0 ACS SYMPOSIUM SERIES
ACS
SYMPOSIUM
SERIES P P POLYMERS IN
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VOLUME 1350 Y
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POLYMER-BASED GENE AND DRUG
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DELIVERY SYSTEMS
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The delivery of genes and drugs remains an active research area, with new U
challenges arising from the need to deliver specialized cargo, including T
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antibodies, peptides, proteins and oligonucleotides and the need of reaching
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desired release profiles. Polymer-based systems hold great promise, as
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polymers can be designed and modified to meet new challenges. Front- L
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line investigators describe polymer systems, such as polyethylenimine,
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poly(thioether anhydrides), stimuli-responsive hydrogels, and metal-organic R
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nanomaterials, to deliver specific therapeutics, such as genetic materials and
anticancer drugs, in controlled manners. Polymer chemists, pharmaceutical
scientists, material chemists, and other researchers will find this collection
valuable for their research.
PUBLISHED BY THE
American Chemical Society
SPONSORED BY THE
ACS Division of Polymer Chemistry, Inc.
FUJIWARA, LIU,
F
OHYA & WANG
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Polymers in Therapeutic Delivery
1350
ACS SYMPOSIUM SERIES
Polymers in Therapeutic Delivery
Tomoko Fujiwara,Editor
The University of Memphis
Memphis, Tennessee
X. Michael Liu,Editor
Glaukos Corporation
San Clemente, California
Yuichi Ohya,Editor
Kansai University
Osaka, Japan
Yongmei Wang,Editor
The University of Memphis
Memphis, Tennessee
Sponsored by the
ACS Division of Polymer Chemistry, Inc.
American Chemical Society, Washington, DC
Library of Congress Cataloging-in-Publication Data
Names: Fujiwara, Tomoko, editor. | Liu, X. Michael, editor. | Ohya, Yuichi,
editor. | Wang, Yongmei, editor.
Title: Polymers in therapeutic delivery / Tomoko Fujiwara, editor, the
University of Memphis, Memphis, Tennessee, X. Michael Liu, editor,
Glaukos Corporation, San Clemente, California, Yuichi Ohya, editor,
Kansai University, Osaka, Japan, Yongmei Wang, editor, the University of
Memphis, Memphis, Tennessee.
Description: Washington, DC : American Chemical Society, [2020] | Series:
ACS symposium series ; 1350 | "Sponsored by the ACS Division of Polymer
Chemistry, Inc" | Includes bibliographical references and index. |
Summary: "This book is about Polymers in Therapeutic Delivery"--
Provided by publisher.
Identifiers: LCCN 2020019070 (print) | LCCN 2020019071 (ebook) | ISBN
9780841238145 (hardcover) | ISBN 9780841298996 (ebook other)
Subjects: LCSH: Polymeric drug delivery systems. | Polymeric drugs.
Classification: LCC RS201.P65 P66 2020 (print) | LCC RS201.P65 (ebook) |
DDC 615.1--dc23
LC record available at https://lccn.loc.gov/2020019070
LC ebook record available at https://lccn.loc.gov/2020019071
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Foreword
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ACS Books
Contents
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
1. A Polymer Physics Perspective on Why PEI Is an Effective Nonviral Gene Delivery
Vector. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Caleb Gallops, Jesse Ziebarth, and Yongmei Wang
2. Comparison of In Vitro Performances of Nanorod and Nanofiber Polyplexes
Prepared from Plasmid DNA and Poly(L-lysine) Terminally Bearing Multi-Arm PEG 13
Ryuta Aono, Kenta Nomura, Eiji Yuba, and Atsushi Harada
3. A Novel Polysaccharide Carrier for Targeted Delivery of Therapeutic
Oligonucleotides to β-Glucan Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Noriko Miyamoto, Shinichi Mochizuki, Nobuaki Fujiwara, Hiroto Izumi, and Kazuo Sakurai
4. Sustained Drug-Releasing Systems Using Temperature-Responsive Injectable
Polymers Containing Liposomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Yuta Yoshizaki, Hiroki Yamamoto, Akinori Kuzuya, and Yuichi Ohya
5. Design of Stimuli-Responsive Polyampholytes and Their Transformation into Micro-
Hydrogels for Drug Delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Robin Rajan, Nathapong Pangkom, and Kazuaki Matsumura
6. Cellular Delivery of Hoechst 33342 Anticancer Drug from Crosslinked
Poly(thioether anhydrides): A Cytotoxicity and Efficacy Study. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Halimatu S. Mohammed, Damien S. K. Samways, and Devon A. Shipp
7. Metal–Organic Nanomaterials for Drug Delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Chung-Hui Huang, Pengyu Chen, X. Michael Liu, and Feng Li
Editors’ Biographies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Indexes
Author Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
vii
Preface
InApril2019,theeditorsorganizedasymposiumon“Polymer-basedGeneandDrugDelivery”
attheAmericanChemicalSocietyNationalMeetinginOrlando,Florida.Geneanddrugdelivery
remainanactiveresearcharea,withnewchallengesarisingfromtheneedfordeliveryofavariety
ofdifferenttypesofdrugsincludingantibodies,peptides,proteins,andoligonucleotides.Polymer-
basedsystemsholdgreatpromiseaspolymerscanbedesignedandmodifiedtomeetnewchallenges.
The symposium had over 40 oral presentations and over 10 poster presentations, with speakers
fromEurope,Japan,Canada,China,andtheUS.Thesessioninvitedpresentersfromindustryand
academiawhoarepushingtheever-changingfieldofgeneanddrugdelivery,includingnewprogress
inenhancingbioavailability,strategiestominimizeimmunogenicity,andvariousdeliveriessystems
forregenerativemedicine,genetherapy,andcelltherapy.Thecollectedchaptersinthisbookreflect
some of the presented works.
The first three chapters focus on gene delivery. Positively charged polymers can facilitate the
delivery of negatively charged genetic materials into cells through the formation of a polyplex.
Successfulgenedelivery,however,needstoovercomeseveralbarriersduringthedeliveryprocess.
Chapter1presentsmolecularsimulationsthatlookintowhypolyethyleneimine(PEI)isasuccessful
nonviralgenedeliveryvector.PEIwasthefirstreportednonviralgenedeliveryvectorthathadhigh
transfection efficiency, a feature that has been attributed to the proton sponge effect. Molecular
simulationsinvestigatedthepresumedprotonspongeeffectandshowedthatPEIpossessesunique
chemical/structural changes that could assist in the successful delivery of genetic materials. The
following chapter (Chapter 2) discusses how polyplex shape impacts uptake and transfection
efficiencyduringgenedelivery.Inthisstudy,theauthorsusemulti-armPEGylatedpoly(L-lysine)
(PLL)blockcopolymerstocontrolthemorphologyofthepolyplexfromnanorodtonanofiber.Itis
shownthat,althoughthecellularuptakeofnanofibersislessthanthatofnanorods,thetransfection
efficiency of nanofibers and nanorods are comparable. It is further discussed that this is due to
thedifferenceinthedissociationandaccessibilityofgeneticmaterialsfortranslationuponcellular
uptake. The real-time polymerase chain reaction confirms that genetic materials have a higher
reactivity in nanofibers than in nanorods. This is followed by another chapter (Chapter 3) where
genetic materials are delivered, not by the usual polycations that form polyplexes with genetic
materialsthroughelectrostaticattractions,butbycomplexationwithanovelpolysaccharide,β-1,3-
D-glucan schizophyllan (SPG), through hydrogen bonding and hydrophobic interactions. SPG
consists of triple helices which can dissociate and reassociate from the three single helices. It is
shown that SPG can form complexes with homopolynucleotides such as poly(dA) or poly(dC).
Thispropertyisutilizedtodelivertherapeuticantisenseoligonucleotidetothecellswithβ-glucan
receptors.
The next four chapters focus on recent innovation and advances in drug delivery systems.
Amongvariousdrugdeliverysystems(Chapter4),hydrogelsareattractivesystemsastheycanbe
implanted with loaded drugs to reach specific targeted sites and release therapeutic agents in a
controlled manner. The hydrogels used for such applications should be biocompatible and
biodegradablewithminimaltoxicityandshouldalsopossessdesirabledrugreleaseprofilesovera
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