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

Journal Article · Wed Jun 15 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.04.010· OSTI ID:21587771

Bhattacharyya, Soumya Sundar; Paul, Saili; De, Arnab; Das, Durba; Samadder, Asmita ^[1]; Boujedaini, Naoual ^[2]

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1. Cytogenetyics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235 (India)
2. Boiron Laboratories, Lyon (France)

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{sub 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. - Graphical abstract: Nanoencapsulated coumarin (NC) were characterized for their size and morphology by scanning electron (SEM) and atomic force microscopies (AFM).The physical interaction of the NC with calf thymus DNA was studied through circular dichroism (CD) spectroscopies, using UV-visible titration and thermal denaturation studies. NC had a concentration dependent interaction with calf thymus DNA, could form a new complex with double helical DNA, increased the T{sub m} value and altered CD spectra of DNA and showed stronger anti-cancer effect than synthetic coumarin. Display Omitted Research Highlights: > Strategy for PLGA nano-encapsulation of a bioactive synthetic coumarin, 4 methyl 7 hydroxy coumarin (SC) is formulated. > Anti-cancer potentials of nano-encapsulated SC (NC) are evaluated in skin papilloma cells A375 through standard protocols. > Data of CD and Tm indicate concentration dependent interactions of NC bringing conformational changes in target DNA. > Particle size of NC and physico-chemical interactions with target DNA show NC as a more potent anti-cancer drug than SC. > NC has less cytotoxic effects, and can cross the blood brain barrier - important features for strategic drug design.

• OSTI ID: 21587771
• Journal Information: Toxicology and Applied Pharmacology, Vol. 253, Issue 3; Other Information: DOI: 10.1016/j.taap.2011.04.010; PII: S0041-008X(11)00149-9; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ATOMIC FORCE MICROSCOPY
BLOOD
BLOOD-BRAIN BARRIER
BRAIN
CALVES
COUMARIN
DNA
HEART
INTERACTIONS
KIDNEYS
LIGHT SCATTERING
LIVER
LUNGS
MELANOMAS
MICE
NANOSTRUCTURES
PARTICLE SIZE
PARTICLES
SCANNING ELECTRON MICROSCOPY
THYMUS
ANIMALS
ANTICOAGULANTS
BIOLOGICAL MATERIALS
BODY
BODY FLUIDS
CARCINOMAS
CARDIOVASCULAR SYSTEM
CATTLE
CENTRAL NERVOUS SYSTEM
DIGESTIVE SYSTEM
DISEASES
DOMESTIC ANIMALS
DRUGS
ELECTRON MICROSCOPY
EPITHELIOMAS
ESTERS
GLANDS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
HETEROCYCLIC OXYGEN COMPOUNDS
LACTONES
LYMPHATIC SYSTEM
MAMMALS
MATERIALS
MICROSCOPY
NEOPLASMS
NERVOUS SYSTEM
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PYRANS
RESPIRATORY SYSTEM
RODENTS
RUMINANTS
SCATTERING
SIZE
VERTEBRATES