Docetaxel/2-hydroxypropyl β -cyclodextrin inclusion complex increases docetaxel solubility and release from a nanochannel drug delivery system

Silvia Ferrati, Eugenia Nicolov, Shyam Bansal, Sharath Hosali, Melissa Landis, Alessandro Grattoni

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Breast cancer remains the second leading cause of cancer deaths for women in the U.S. The need for new and alternative strategies to treat this cancer is imperative. Here we show the optimization of our nanochannel delivery system (nDS) for constant and sustained delivery of docetaxel (DTX) for thetreatment of triple negative breast cancer. DTX is a highly hydrophobic drug, making it difficult to reach the therapeutic levels when released in aqueous solutions from our implantable delivery system. To overcome this challenge and test the release of DTX from nDS, we prepared DTX/2-hydroxypropyl β-cyclodextrin (DTX/HPCD) inclusion complexes in different molar ratios. The 1:10 DTX/HPCD complex achieved 5 times higher solubility than the 1:2 complex and 3 times higher in vitro release of DTX than with free DTX. When released in SCID/Beige mice from nanochannel system, the DTX/HPCD complex showed reduced tumor growth, comparable to the standard bolus injections of DTX, indicating that the structural stability and biological activity of DTX were retained in the complex, after its diffusion through the nanochannel system.

Original languageEnglish (US)
Pages (from-to)1645-1649
Number of pages5
JournalCurrent Drug Targets
Volume16
Issue number14
DOIs
StatePublished - 2015

Keywords

  • Cyclodextrin
  • Docetaxel
  • Drug delivery
  • Inclusion complexes
  • Nanochannel implants
  • Sustained release

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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