Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity

Daniel Scott, J&uuml;rgen Rohr, Younsoo BaeDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USAAbstract: Mithramycin (MTM), a natural product of soil bacteria from the Streptomyces genus, displays potent anticancer activity but has been limit...

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Autores principales:	Scott D, Rohr J, Bae Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2c304e14278a4206b027d7af959dca2f
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spelling	oai:doaj.org-article:2c304e14278a4206b027d7af959dca2f2021-12-02T07:22:51ZNanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity1176-91141178-2013https://doaj.org/article/2c304e14278a4206b027d7af959dca2f2011-11-01T00:00:00Zhttp://www.dovepress.com/nanoparticulate-formulations-of-mithramycin-analogs-for-enhanced-cytot-a8610https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Daniel Scott, J&uuml;rgen Rohr, Younsoo BaeDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USAAbstract: Mithramycin (MTM), a natural product of soil bacteria from the Streptomyces genus, displays potent anticancer activity but has been limited clinically by severe side effects and toxicities. Engineering of the MTM biosynthetic pathway has produced the 3-side-chain-modified analogs MTM SK (SK) and MTM SDK (SDK), which have exhibited increased anticancer activity and improved therapeutic index. However, these analogs still suffer from low bioavailability, short plasma retention time, and low tumor accumulation. In an effort to aid with these shortcomings, two nanoparticulate formulations, poly(ethylene glycol)-poly(aspartate hydrazide) self-assembled and cross-linked micelles, were investigated with regard to the ability to load and pH dependently release the drugs. Micelles were successfully formed with both nanoparticulate formulations of each drug analog, with an average size of 8.36 &plusmn; 3.21 and 12.19 &plusmn; 2.77 nm for the SK and SDK micelles and 29.56 &plusmn; 4.67 nm and 30.48 &plusmn; 7.00 nm for the SK and SDK cross-linked micelles respectively. All of the drug-loaded formulations showed a pH-dependent release of the drugs, which was accelerated as pH decreased from 7.4 to 5.0. The micelles retained biological activity of SK and SDK entrapped in the micelles, suppressing human A549 lung cancer cells effectively.Keywords: drug delivery, polymer micelles, controlled release, MTM, cancer chemotherapyScott DRohr JBae YDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2757-2767 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Scott D Rohr J Bae Y Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity
description	Daniel Scott, J&uuml;rgen Rohr, Younsoo BaeDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USAAbstract: Mithramycin (MTM), a natural product of soil bacteria from the Streptomyces genus, displays potent anticancer activity but has been limited clinically by severe side effects and toxicities. Engineering of the MTM biosynthetic pathway has produced the 3-side-chain-modified analogs MTM SK (SK) and MTM SDK (SDK), which have exhibited increased anticancer activity and improved therapeutic index. However, these analogs still suffer from low bioavailability, short plasma retention time, and low tumor accumulation. In an effort to aid with these shortcomings, two nanoparticulate formulations, poly(ethylene glycol)-poly(aspartate hydrazide) self-assembled and cross-linked micelles, were investigated with regard to the ability to load and pH dependently release the drugs. Micelles were successfully formed with both nanoparticulate formulations of each drug analog, with an average size of 8.36 &plusmn; 3.21 and 12.19 &plusmn; 2.77 nm for the SK and SDK micelles and 29.56 &plusmn; 4.67 nm and 30.48 &plusmn; 7.00 nm for the SK and SDK cross-linked micelles respectively. All of the drug-loaded formulations showed a pH-dependent release of the drugs, which was accelerated as pH decreased from 7.4 to 5.0. The micelles retained biological activity of SK and SDK entrapped in the micelles, suppressing human A549 lung cancer cells effectively.Keywords: drug delivery, polymer micelles, controlled release, MTM, cancer chemotherapy
format	article
author	Scott D Rohr J Bae Y
author_facet	Scott D Rohr J Bae Y
author_sort	Scott D
title	Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity
title_short	Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity
title_full	Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity
title_fullStr	Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity
title_full_unstemmed	Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity
title_sort	nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/2c304e14278a4206b027d7af959dca2f
work_keys_str_mv	AT scottd nanoparticulateformulationsofmithramycinanalogsforenhancedcytotoxicity AT rohrj nanoparticulateformulationsofmithramycinanalogsforenhancedcytotoxicity AT baey nanoparticulateformulationsofmithramycinanalogsforenhancedcytotoxicity
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Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity

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