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

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, USAA...

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Autores principales: Sabnis N, Nair M, Israel M, McConathy WJ, Lacko AG
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Publicado: Dove Medical Press 2012
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spelling oai:doaj.org-article:d42758bfaba747239efc45d1bbe3b8ae2021-12-02T02:14:38ZEnhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles1176-91141178-2013https://doaj.org/article/d42758bfaba747239efc45d1bbe3b8ae2012-02-01T00:00:00Zhttp://www.dovepress.com/enhanced-solubility-and-functionality-of-valrubicin-ad-32-against-canc-a9318https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Nirupama 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 deliverySabnis N, Nair MIsrael MMcConathy WJLacko AGDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 975-983 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Sabnis N, Nair M
Israel M
McConathy WJ
Lacko AG
Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles
description 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
format article
author Sabnis N, Nair M
Israel M
McConathy WJ
Lacko AG
author_facet Sabnis N, Nair M
Israel M
McConathy WJ
Lacko AG
author_sort Sabnis N, Nair M
title Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles
title_short Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles
title_full Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles
title_fullStr Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles
title_full_unstemmed Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles
title_sort enhanced solubility and functionality of valrubicin (ad-32) against cancer cells upon encapsulation into biocompatible nanoparticles
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/d42758bfaba747239efc45d1bbe3b8ae
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