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.