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

Kyeongsoon Park, Jong Ho Kim, Yun Sik Nam, Seulki Lee, Hae Yun Nam, Kwang Meyung Kim, Jae Hyung Park, In-San Kim, Kuiwon Choi, Sang Yoon Kim, Ick Chan Kwon

Research output: Contribution to journalArticle

187 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)305-314
Number of pages10
JournalJournal of Controlled Release
Volume122
Issue number3
DOIs
Publication statusPublished - 2007 Oct 8
Externally publishedYes

Fingerprint

Nanoparticles
Polymers
Molecular Weight
Neoplasms
Blood Circulation Time
glycol-chitosan
Blood Circulation
Optical Imaging
Tissue Distribution
Particle Size
Pharmacokinetics
cholanic acid

Keywords

  • Glycol chitosan nanoparticle
  • Polymer molecular weight
  • Tissue distribution
  • Tumor targeting

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles. / Park, Kyeongsoon; Kim, Jong Ho; Nam, Yun Sik; Lee, Seulki; Nam, Hae Yun; Kim, Kwang Meyung; Park, Jae Hyung; Kim, In-San; Choi, Kuiwon; Kim, Sang Yoon; Kwon, Ick Chan.

In: Journal of Controlled Release, Vol. 122, No. 3, 08.10.2007, p. 305-314.

Research output: Contribution to journalArticle

Park, Kyeongsoon ; Kim, Jong Ho ; Nam, Yun Sik ; Lee, Seulki ; Nam, Hae Yun ; Kim, Kwang Meyung ; Park, Jae Hyung ; Kim, In-San ; Choi, Kuiwon ; Kim, Sang Yoon ; Kwon, Ick Chan. / Effect of polymer molecular weight on the tumor targeting characteristics of self-assembled glycol chitosan nanoparticles. In: Journal of Controlled Release. 2007 ; Vol. 122, No. 3. pp. 305-314.
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AB - 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.

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