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

Nirupama Sabnis, Maya P. Nair, Mervyn Israel, Walter J. McConathy, Andras G. Lacko

Research output: Contribution to journalArticleResearchpeer-review

33 Citations (Scopus)

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 (IC50) 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 IC50 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. 2012 Cárdenas et al, publisher and licensee Dove Medical Press Ltd.

Original languageEnglish
Pages (from-to)975-983
Number of pages9
JournalInternational Journal of Nanomedicine
Volume7
DOIs
StatePublished - 5 Dec 2012

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valrubicin
Lipoproteins
Encapsulation
Nanoparticles
Solubility
Cells
HDL Lipoproteins
Neoplasms
Inhibitory Concentration 50
Drug delivery
Toxicity
Pharmaceutical Preparations

Keywords

  • AD-32
  • Nanoparticles
  • Selective drug delivery
  • Targeted drug delivery
  • rHDL

Cite this

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title = "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 (IC50) 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 IC50 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. 2012 C{\'a}rdenas et al, publisher and licensee Dove Medical Press Ltd.",
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Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles. / Sabnis, Nirupama; Nair, Maya P.; Israel, Mervyn; McConathy, Walter J.; Lacko, Andras G.

In: International Journal of Nanomedicine, Vol. 7, 05.12.2012, p. 975-983.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles

AU - Sabnis, Nirupama

AU - Nair, Maya P.

AU - Israel, Mervyn

AU - McConathy, Walter J.

AU - Lacko, Andras G.

PY - 2012/12/5

Y1 - 2012/12/5

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KW - Nanoparticles

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