4.4 Article

Thermosensitive biotinylated hydroxypropyl cellulose-based polymer micelles as a nano-carrier for cancer-targeted drug delivery

Journal

JOURNAL OF POLYMER RESEARCH
Volume 21, Issue 10, Pages -

Publisher

SPRINGER
DOI: 10.1007/s10965-014-0567-4

Keywords

Cancer-targeted drug delivery; Paclitaxel; Tumor-targeted chemotherapy; Polymeric micelles

Funding

  1. Iran National Science Foundation
  2. Azarbaijan Shahid Madani University Research Council

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In this article, we report the synthesis of a novel amphiphilic hydroxypropyl cellulose-based polymer (HPC-PEG- Chol) that contained poly (ethylene glycol) and cholesterol-containing moieties with specific degrees of substitution. The resulting polymer was subsequently converted to a biotin conjugate (HPC-PEG-Chol-biotin), to develop a new potential cancer-targeted drug delivery system. The biotin conjugate was used to prepare micelles via the dialysis method. The polymeric micelles in aqueous solution presented a lower critical solution temperature (LCST) of 39.8 degrees C. The critical micelle concentration (CMC) values of the polymeric micelles at 25 and 45 degrees C were evaluated to be about 0.32 and 0. 25 g/L, respectively. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses of the micelles revealed the spherical shapes of the micelles, with 84 nm mean diameters that increased with the increase of the temperature above LCST. The hydrophobic anticancer drug paclitaxel (PTX) was loaded in the micelles and the in vitro release behaviors of PTX were investigated at different temperatures. The release profile of PTX from the polymeric micelles revealed a thermosensitivity, since its release rate was higher at 41 degrees C than at 37 degrees C. Fluorescent microscopy analyses confirm that the PTX-loaded HPC-PEG-Chol-biotin is superior in cellular uptake, with very strong adsorption to both HeLa and MDA-MB-231 cancer cell lines. MTT assay in normal cells indicated that HPC-PEG-Chol-biotin micelles have great potential to be safely used in tumortargeting chemotherapy.

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