Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles
| Autor: | Mervyn Israel, Andras G. Lacko, Nirupama Sabnis, Maya Nair, Walter J. McConathy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
AD-32
Materials science Cell Survival selective drug delivery Biophysics Pharmaceutical Science Bioengineering Pharmacology Nanocapsules targeted drug delivery Cell Line Biomaterials Inhibitory Concentration 50 Drug Stability International Journal of Nanomedicine Cell Line Tumor Drug Discovery medicine Humans Doxorubicin Particle Size IC50 Valrubicin Original Research rHDL Bladder cancer Organic Chemistry Temperature General Medicine medicine.disease Targeted drug delivery Solubility Cancer cell Nanoparticles Nanocarriers Lipoproteins HDL medicine.drug |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 1176-9114 |
| Popis: | Nirupama Sabnis1, Maya Nair1, Mervyn Israel2, Walter J McConathy3, Andras G Lacko11University of North Texas Health Science Center, Fort Worth, TX, 2University of Tennessee Health Science Center, Memphis, TN, 3Texas Tech University Health Sciences Center–Permian Basin, Odessa, TX, USAAbstract: 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.Keywords: AD-32, rHDL, nanoparticles, targeted drug delivery, selective drug delivery |
| Databáze: | OpenAIRE |
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