Abstract
The use of different nanoparticles (NPs) for successful encapsulation of bioactive substances is discussed. The inclusion efficiency into liposomes, acetalated dextran (Ac-Dex), and variants of poly[(lactic acid)-co-(glycolic acid)] (PLGA) NPs is analyzed after chemical degradation. Efficient inclusion of SIRT1 inhibitor Ex527 in liposomes, Ac-Dex- and PLGA-NPs is observed for all procedures used. Activity of Ex527 is demonstrated by monitoring the acetylation status of SIRT1-target p53. In contrast, small peptides are only incorporated into acid-terminated PLGA-NPs and marginally into Ac-Dex-NPs. The yield depends on peptide sequence and terminal modifications. Activity is exemplified for angiotensin II using the dynamic mass redistribution technology.
Keywords:
HDAC inhibitors; cellular uptake; liposomes; nanoparticles; peptide drugs.
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Angiotensin II / chemistry
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Angiotensin II / pharmacology
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Carbazoles / chemistry*
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Carbazoles / pharmacology
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Dextrans / chemistry
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Drug Carriers / chemistry
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HEK293 Cells / drug effects
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Histone Deacetylase Inhibitors / chemistry*
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Histone Deacetylase Inhibitors / pharmacology
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Humans
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Hydroxamic Acids / chemistry
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Lactic Acid / chemistry
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Liposomes / chemistry*
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Liposomes / pharmacology
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Nanoparticles / chemistry*
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Peptides / chemistry*
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Polyglycolic Acid / chemistry
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Polylactic Acid-Polyglycolic Acid Copolymer
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Sirtuin 1 / antagonists & inhibitors
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Valproic Acid / chemistry
Substances
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6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
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Carbazoles
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Dextrans
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Drug Carriers
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Liposomes
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Peptides
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Angiotensin II
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polyglycolic Acid
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Lactic Acid
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trichostatin A
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Valproic Acid
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SIRT1 protein, human
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Sirtuin 1