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 (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.affiliation: Department of Molecular Biology/Immunology, University of North TexasHealth Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Sabnis
authors.forename: Maya
authors.initials: M
authors.lastname: Nair
authors.forename: Mervyn
authors.initials: M
authors.lastname: Israel
authors.forename: Walter J
authors.initials: WJ
authors.lastname: McConathy
authors.forename: Andras G
authors.initials: AG
authors.lastname: Lacko
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004355:Drug Stability; D006801:Humans; D020128:Inhibitory Concentration 50; D008075:Lipoproteins, HDL / Q000737:chemistry; D053769:Nanocapsules / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D013696:Temperature
chemical_list: D008075:Lipoproteins, HDL; D053769:Nanocapsules; C016163:valrubicin; D004317:Doxorubicin