title: 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.
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.
authors.affiliation: Cytogenetyics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235, India.
authors.forename: Soumya Sundar
authors.initials: SS
authors.lastname: Bhattacharyya
authors.forename: Saili
authors.initials: S
authors.lastname: Paul
authors.forename: Arnab
authors.initials: A
authors.lastname: De
authors.forename: Durba
authors.initials: D
authors.lastname: Das
authors.forename: Asmita
authors.initials: A
authors.lastname: Samadder
authors.forename: Naoual
authors.initials: N
authors.lastname: Boujedaini
authors.forename: Anisur Rahman
authors.initials: AR
authors.lastname: Khuda-Bukhsh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003374:Coumarins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D006801:Humans; D020287:In Situ Nick-End Labeling; D019344:Lactic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D053769:Nanocapsules; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA; C427203:calf thymus DNA