Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles

Authors
Park, KyeongsoonKim, Jong-HoNam, Yun SikLee, SeulkiNam, Hae YunKim, KwangmeyungPark, Jae HyungKim, In-SanChoi, KuiwonKim, Sang YoonKwon, Ick Chan
Issue Date
2007-10-08
Publisher
ELSEVIER
Citation
JOURNAL OF CONTROLLED RELEASE, v.122, no.3, pp.305 - 314
Abstract
To improve the in vivo tumor targeting characteristics of polymeric nanoparticles, three glycol chitosan (GC-20 kDa, GC-100 kDa, and GC-250 kDa) derivatives with different molecular weights were modified with cholanic acid at the same molar ratio, The resulting amphiphilic glycol chitosan-cholanic acid conjugates self-assembled to form glycol chitosan nanoparticles (GC-20 kDa-NP, GC-100 kDa-NP, and GC-250 kDa-NP) under aqueous conditions. The physicochemical properties of all three glycol chitosan nanoparticles, including degree of substitution with cholanic acid, surface charge, particle size and in vitro stability, were similar regardless of molecular weight. In vivo tissue distribution, time-dependent excretion, and tumor accumulation of glycol chitosan nanoparticles labeled with the near-infrared (NIR) fluorophore, Cy5.5, were monitored in SCC7 tumor-bearing mice, using NIR fluorescence imaging systems. Glycol chitosan nanoparticles displayed prolonged blood circulation time, decreased time-dependent excretion from the body, and elevated tumor accumulation with increasing polymer molecular weight. The results collectively suggest that high molecular weight glycol chitosan nanoparticles remain for longer periods in the blood circulation, leading to increased accumulation at the tumor site. Accordingly, we propose that enhanced tumor targeting by high molecular weight glycol chitosan nanoparticles is related to better in vivo stability, based on a pharmacokinetic improvement in blood circulation time. (c) 2007 Elsevier B.V. All rights reserved.
Keywords
MACROMOLECULAR THERAPEUTICS; ACID; BIODISTRIBUTION; LIPOSOMES; CARRIERS; MACROMOLECULAR THERAPEUTICS; ACID; BIODISTRIBUTION; LIPOSOMES; CARRIERS; glycol chitosan nanoparticle; polymer molecular weight; tissue distribution; tumor targeting
ISSN
0168-3659
URI
https://pubs.kist.re.kr/handle/201004/134046
DOI
10.1016/j.jconrel.2007.04.009
Appears in Collections:
KIST Article > 2007
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