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Polyethylene glycol-modified arachidyl chitosan-based nanoparticles for prolonged blood circulation of doxorubicin.

Abstract
Doxorubicin (DOX)-loaded nanoparticles based on polyethylene glycol-conjugated chitosan oligosaccharide-arachidic acid (CSOAA-PEG) were explored for potential application to leukemia therapy. PEG was conjugated with CSOAA backbone via amide bond formation and the final product was verified by (1)H NMR analysis. Using the synthesized CSOAA-PEG, nanoparticles having characteristics of a 166-nm mean diameter, positive zeta potential, and spherical shape were produced for the delivery of DOX. The mean diameter of CSOAA-PEG nanoparticles in the serum solution (50% fetal bovine serum) remained relatively constant over 72 h as compared with CSOAA nanoparticles (changes of 20.92% and 223.16%, respectively). The sustained release pattern of DOX from CSOAA-PEG nanoparticles was displayed at physiological pH, and the release rate increased under the acidic pH conditions. The cytotoxicity of the CSOAA-PEG conjugate was negligible in human leukemia cells (K562) at the concentrations tested (∼ 100 μg/ml). The uptake rate of DOX from the nanoparticles by K562 cells was higher than that from the solution. Judging from the results of pharmacokinetic studies in rats, in vivo clearance rate of DOX from the CSOAA-PEG nanoparticle group was slower than other groups, subsequently extending the circulation period. The PEGylated CSOAA-based nanoparticles could represent an effective nano-sized delivery system for DOX which has been used for the treatment of blood malignancies.
AuthorsUbonvan Termsarasab, In-Soo Yoon, Ju-Hwan Park, Hyun Tae Moon, Hyun-Jong Cho, Dae-Duk Kim
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 464 Issue 1-2 Pg. 127-34 (Apr 10 2014) ISSN: 1873-3476 [Electronic] Netherlands
PMID24451239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Drug Carriers
  • Eicosanoic Acids
  • Polyethylene Glycols
  • Doxorubicin
  • Chitosan
  • arachidic acid
Topics
  • Animals
  • Cell Line, Tumor
  • Chitosan (chemistry)
  • Doxorubicin (chemistry)
  • Drug Carriers (chemistry)
  • Eicosanoic Acids (chemistry)
  • Humans
  • K562 Cells
  • Male
  • Nanoparticles (chemistry)
  • Polyethylene Glycols (chemistry)
  • Rats
  • Rats, Sprague-Dawley

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