Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles

Int J Nanomedicine. 2012;7:975-83. doi: 10.2147/IJN.S28029. Epub 2012 Feb 22.


Among numerous drug-delivery approaches, reconstituted high-density lipoprotein (rHDL) nanocarriers have proven particularly applicable for delivering highly hydrophobic drugs. In this study, we have investigated the enhancement of the therapeutic impact of valrubicin (AD-32), an antineoplastic agent that has been limited to intravesicular application against bladder cancer, despite the encouraging original preclinical data. Earlier studies validated the superior therapeutic efficacy of AD-32 over doxorubicin. In the present study, rHDL/AD-32 nanoparticles were formulated and characterized with regard to encapsulation efficiency, physicochemical properties, selective toxicity, and receptor-mediated uptake. The half maximal inhibitory concentration values (IC(50)) for rHDL/AD-32 nanoparticles were 1.8 and 2.6 times lower than the free AD-32 for prostate (PC-3) and ovarian (SKOV-3) cancer cell lines, respectively, whereas nonmalignant cell lines demonstrated 5 and 1.48 times higher IC(50) doses with rHDL/AD-32 formulations. The data obtained demonstrated effective receptor- mediated uptake of AD-32 from the rHDL nanocarriers by PC-3 and SKOV-3 cancer cells via a targeted drug-delivery process. The rHDL/AD-32 formulation was stable for 6 months when stored at 4°C or at -20°C, as 92% of the AD-32 was retained in the nanoparticles. The findings from this study show that the rHDL/AD-32 formulation can overcome the solubility barriers of AD-32 and thus serve as an effective systemically administered chemotherapeutic agent.

Keywords: AD-32; nanoparticles; rHDL; selective drug delivery; targeted drug delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Drug Stability
  • Humans
  • Inhibitory Concentration 50
  • Lipoproteins, HDL / chemistry
  • Nanocapsules / chemistry
  • Nanoparticles / chemistry*
  • Particle Size
  • Solubility
  • Temperature


  • Lipoproteins, HDL
  • Nanocapsules
  • valrubicin
  • Doxorubicin