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Poly (lactide-co-glycolide) acid nanoencapsulation of a synthetic coumarin: cytotoxicity and bio-distribution in mice, in cancer cell line and interaction with calf thymus DNA as target.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2011 Jun 15; Vol. 253 (3), pp. 270-81. Date of Electronic Publication: 2011 Apr 28. - Publication Year :
- 2011
-
Abstract
- Several naturally occurring coumarin compounds, including scopoletin (7 hydroxy-6 methoxycoumarin), of plant origin have been reported to have anti-cancer potentials. A related but chemically synthesized coumarin, 4-methyl-7-hydroxy coumarin (SC), was also shown to have similar anti-cancer potentials. In the present study, to test if nano-encapsulated SC could be a more potent anti-cancer agent, we encapsulated SC with poly lactide-co-glycolide acid (PLGA) nanoparticles (Nano Coumarin; NC) and tested its potentials with a variety of protocols. NC demonstrated greater efficiency of drug uptake and showed anti-cancer potentials in melanoma cell line A375, as revealed from scanning electronic and atomic force microscopies. To test its possible interaction with target DNA, the combined data of circular dichroism spectra (CD) and melting temperature profile (T(m)) of calf thymus DNA treated with NC were analyzed. Results indicated a concentration dependent interaction of NC with calf thymus DNA, bringing in effective change in structure and conformation, and forming a new complex that increased its stability. Particle size and morphology of NC determined through polydispersity index and zeta potential using dynamic light scattering qualified NC to be a more potent anti-cancer agent than SC. Further, SC and NC showed negligible cytotoxic effects on normal skin cells and peripheral blood mononuclear cells of mice. Distribution assay of PLGA nanoparticles in different tissues like brain, heart, kidneys, liver, lungs, and spleen in mice revealed the presence of nanoparticles in different tissues including brain, indicating that the particles could cross the blood brain barrier, significant information for drug design.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Cattle
Cell Line, Tumor
Cell Survival drug effects
Circular Dichroism
Coumarins pharmacokinetics
Coumarins pharmacology
Humans
In Situ Nick-End Labeling
Lactic Acid pharmacokinetics
Mice
Polyglycolic Acid pharmacokinetics
Polylactic Acid-Polyglycolic Acid Copolymer
Reverse Transcriptase Polymerase Chain Reaction
Tissue Distribution
Antineoplastic Agents administration & dosage
Coumarins administration & dosage
DNA chemistry
Lactic Acid administration & dosage
Nanocapsules administration & dosage
Polyglycolic Acid administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0333
- Volume :
- 253
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21549736
- Full Text :
- https://doi.org/10.1016/j.taap.2011.04.010