Strategic formulation of apigenin-loaded PLGA nanoparticles for intracellular trafficking, DNA targeting and improved therapeutic effects in skin melanoma in vitro.

Abstract

The aim of the present study was the evaluation of anti-proliferative potentials of apigenin (Ap), (a dietary flavonoid) loaded in poly (lactic-co-glycolide) nanoparticles (NAp) in A375 cells in vitro. NAp was characterized for particle size, morphology, zeta potential, drug release and encapsulation. Cellular entry and intracellular localization of NAp were assessed by transmission electron and confocal microscopies. Circular dichroic spectral analysis and stability curve for Gibb's free energy of dsDNA of A375 cells were also analyzed. DNA fragmentation, intracellular ROS accumulation, superoxide-dismutase activity, intracellular glutathione-reductase content and mitochondrial functioning through relevant markers like mitochondrial transmembrane potential, ATPase activity, ATP/ADP ratio, volume changes/swelling, cytochrome-c release, expressions of Apaf-1, bax, bcl-2, caspase-9, 3, and PARP cleavage were analyzed. NAp produced better effects due to their smaller size, faster mobility and site-specific action. Photostability studies revealed that PLGA encapsulations were efficient at preserving apigenin ultraviolet-light mediated photodegradation. NAp readily entered cancer cells, could intercalate with dsDNA, inducing conformational change. Corresponding increase in ROS accumulation and depletion of the antioxidant enzyme activities exacerbated DNA damage, mediating apoptosis through mitochondrial dysfunction. Overall results indicate that therapeutic efficacy of NAp may be enhanced by PLGA nanoparticle formulations to have better ameliorative potentials in combating skin melanoma.

• Authors: Sreemanti Das, Jayeeta Das, Asmita Samadder, Avijit Paul, Anisur Rahman Khuda-Bukhsh
• Journal: Toxicology letters (Toxicol Lett) Vol. 223 Issue 2 Pg. 124-38 (Nov 25 2013) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 24070738 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• APAF1 protein, human
• Apoptotic Protease-Activating Factor 1
• BAX protein, human
• Reactive Oxygen Species
• bcl-2-Associated X Protein
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Apigenin
• Cytochromes c
• CASP3 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 9

Topics

• Apigenin (chemistry, pharmacology)
• Apoptosis (drug effects)
• Apoptotic Protease-Activating Factor 1 (genetics, metabolism)
• Caspase 3 (genetics, metabolism)
• Caspase 9 (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chemistry, Pharmaceutical
• Cytochromes c (genetics, metabolism)
• DNA Fragmentation (drug effects)
• Humans
• Lactic Acid (chemistry)
• Melanoma (drug therapy)
• Mitochondria (drug effects, metabolism)
• Nanoparticles (chemistry)
• Particle Size
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Reactive Oxygen Species (metabolism)
• Skin Neoplasms
• bcl-2-Associated X Protein (genetics, metabolism)