Biomedical Engineering Reference
In-Depth Information
CHAPTER 8
DESIGN AND SYNTHESIS OF ENDOSOMOLYTIC CONJUGATED
POLYASPARTAMIDE FOR CYTOSOLIC DRUG DELIVERY
Kwangwon Seo and Dukjoon Kim
*
Department of Chemical Engineering, Sungkyunkwan University, 300 Chunchun-dong,
Jangan-gu, Suwon, Kyungki-do, 440-746, Korea
*
E-mail: djkim@skku.edu
1. Introduction
As interest in intracellular delivery of macromolecular therapeutics such as
plasmid DNA, oligonucleotides (ODNs), ribozymes, anticancer drugs, and
immunotoxins have increased through development of biotechnology and
nanotechnology, various drug carriers for efficient delivery have been
extensively studied.[1-4] When the drug carriers are internalized into cells
via
specific (receptor-mediated) or non-specific (adsorptive) endocytosis, they are
trafficked to the endosome and eventually degraded by acid-catalyzed lysosomal
enzymes or recycled back to the plasma membrane; this intracellular pathway is
shown in Figure 1. It was well known that the internal pH of the compartments
decreases from 7.2 to 5.5 from endosome to lysosome. Therefore, it is required to
release the drug into the cytosol after endosomal escape by membrane fusion or
disruption using the acidic pH in the endosome to achieve an enhanced
therapeutic effect.[5, 7]
A variety of endosomolyic polymers, especially pH-sensitive polymers, have
been studied as intracellular drug delivery carriers for the past decades;
representatively, they are: poly(ethylene imine)s (PEI)[8]; imidazole-related
polymers[9]; poly(amidoamine)s and related polymers [10, 11]; poly[2-
(dimethylaminoethyl) methacrylate (pDMAEMA)-based polymers[12] as
cationic polymer systems and poly(acrylic acid) [13, 14] as anionic polymer
systems. Nevertheless, these polymer carriers have some drawbacks regarding
their drug delivery applications, such as difficult syntheses, toxicity, low
transfection efficiency, and non-biodegradability. Though the mechanism of this
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