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

Abstract

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.

• Authors: Nirupama Sabnis, Maya Nair, Mervyn Israel, Walter J McConathy, Andras G Lacko
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 7 Pg. 975-83 ( 2012) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 22393294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipoproteins, HDL
• Nanocapsules
• valrubicin
• Doxorubicin

Topics

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