Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paclitaxel: Synthesis, characterization, and in vivo biodistribution

G. Saravanakumar, Kyung Hyun Min, Dong Sik Min, Ah Young Kim, Chang Moon Lee, Yong Woo Cho, Sang Cheon Lee, Kwangmeyung Kim, Seo Young Jeong, Kinam Park, Jae Hyung Park, Ick Chan Kwon

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Abstract

Development of successful formulations for poorly water-soluble drugs remains a longstanding critical and challenging issue in cancer therapy. As a potential drug carrier of paclitaxel, hydrotropic oligomer-glycol chitosan (HO-GC) was synthesized by chemical conjugation of the N,N-diethylnicotinamide-based oligomer, uniquely designed for enhancing the aqueous solubility of paclitaxel, to the backbone of glycol chitosan. Owing to its amphiphilicity, the conjugate formed self-assembled nanoparticles with a mean diameter of 313 ± 13 nm in a phosphate-buffered saline (PBS, pH 7.4 at 37 °C). HO-GC nanoparticles maintained their structure for up to 50 days in PBS. They could encapsulate a high quantity (20 wt.%) of paclitaxel (PTX) with a maximum drug-loading efficiency of 97%, due to the presence of hydrotropic inner cores. When HO-GC-PTX particles were exposed to the 0.1 M sodium salicylate solution in PBS (pH 7.4), PTX was released from nanoparticles in a sustained manner. From the cytotoxicity test, it was confirmed that HO-GC-PTX nanoparticles showed lower cytotoxicity than free PTX formulation in 50%/50% Cremophor EL/ethanol mixture. The optical imaging results indicated that near-infrared fluorescence dye (Cy5.5)-labeled HO-GC-PTX showed an excellent tumor specificity in SCC7 tumor-bearing mice, due to the enhanced permeation and retention effect. Overall, HO-GC-PTX nanoparticles might be a promising carrier for PTX delivery in cancer therapy.

Original languageEnglish
Pages (from-to)210-217
Number of pages8
JournalJournal of Controlled Release
Volume140
Issue number3
DOIs
Publication statusPublished - 2009 Dec 16

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Keywords

  • Cancer therapy
  • Glycol chitosan
  • Hydrotropic oligomer
  • Paclitaxel
  • Self-assembled nanoparticles

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Saravanakumar, G., Min, K. H., Min, D. S., Kim, A. Y., Lee, C. M., Cho, Y. W., Lee, S. C., Kim, K., Jeong, S. Y., Park, K., Park, J. H., & Kwon, I. C. (2009). Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paclitaxel: Synthesis, characterization, and in vivo biodistribution. Journal of Controlled Release, 140(3), 210-217. https://doi.org/10.1016/j.jconrel.2009.06.015