title: Purely aqueous PLGA nanoparticulate formulations of curcumin exhibit enhanced anticancer activity with dependence on the combination of the carrier.
abstract: Curcumin, a yellow pigment present in turmeric, possess potential anti-proliferative and anti-inflammatory activities but poor aqueous solubility limits its applications. In this study we report a novel comparative study of the formulation and characterization of curcumin nanoparticles (nanocurcumin) using two poly (lactide-co-glycolide) (PLGA) combinations, 50:50 and 75:25 having different lactide to glycolide ratios. Nanocurcumin 50:50 showed smaller size with higher encapsulation efficiency. Thermal evaluation suggested the presence of curcumin in molecular dispersion form which supported its sustained release up to a week where nanocurcumin 50:50 showed faster release. Cellular uptake studies in human epithelial cervical cancer cells (HeLa) exhibited enhanced intracellular fluorescence with nanocurcumin when compared to free curcumin, when both given in purely aqueous media. Antiproliferative studies using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, Annexin V/propidium iodide staining, poly (ADP-ribose) polymerase (PARP) cleavage and downregulation of clonogenic potential of HeLa cells proved the better antitumor activity of nanocurcumin 50:50 administered in aqueous media. Superior efficacy of nanocurcumin 50:50 in comparison to free curcumin was further demonstrated by electrophoretic mobility shift assay and immunocytochemical analysis. In conclusion, the enhanced aqueous solubility and higher anticancer efficacy of nanocurcumin administered in aqueous media clearly demonstrates its potential against cancer chemotherapy, with dependence on the combination of PLGA.
authors.affiliation: Chemical Biology, Molecular Medicine Division, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: K Lekha
authors.initials: KL
authors.lastname: Nair
authors.forename: Arun Kumar T
authors.initials: AK
authors.lastname: Thulasidasan
authors.forename: G
authors.initials: G
authors.lastname: Deepa
authors.forename: Ruby John
authors.initials: RJ
authors.lastname: Anto
authors.forename: G S Vinod
authors.initials: GS
authors.lastname: Kumar
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D051996:Transcription Factor RelA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011065:Poly(ADP-ribose) Polymerases; D003474:Curcumin