Cytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo.

Abstract

Poor oral bioavailability of chelidonine, a bio-active ingredient of Chelidonium majus, showing anti-cancer potentials against cancer cells with multidrug resistance, makes its optimal use rather limited. To address this problem, we encapsulated chelidonine in biodegradable poly(lactide-co-glycolide) (PLGA) polymers and evaluated nano-chelidonine's (NCs) anti-cancer efficacy vis-à-vis free chelidonine (FC) against HepG2 cells and also evaluated its bioavailability in mice. Physicochemical characteristics indicated that stable spherical NC were formed in nanometer size range (123±1.15 nm) with good yield (86.34±1.91%), better encapsulation efficiency (82.6±0.574%), negative surface charge (-19.6±2.48 mV) and ability of prolonged and sustained release of chelidonine. Fourier transform infrared analysis revealed that NC resembled similar peaks as that of FC suggesting effective encapsulation in PLGA. NC exhibited rapid cellular uptake and stronger apoptotic effect (∼46.6% reduced IC₅₀ value) than FC, blocking HepG2 cells at G2/M phase. p53, cyclin-D1, Bax, Bcl-2, cytochrome c, Apaf-1, caspase-9 and caspase-3 expressions also corroborated well to suggest greater anticancer potentials of NC. Our in vivo studies demonstrated NC to be more bio-available than FC and showed a better tissue distribution profile without inducing any toxicity (100 mg/kg bw) in mice. Unlike FC, NC could permeate into brain tissue, indicating thereby NC's better potentials for use in therapeutic oncology.

• Authors: Avijit Paul, Sreemanti Das, Jayeeta Das, Asmita Samadder, Anisur Rahman Khuda-Bukhsh
• Journal: Toxicology letters (Toxicol Lett) Vol. 222 Issue 1 Pg. 10-22 (Sep 12 2013) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 23850776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Benzophenanthridines
• Central Nervous System Depressants
• Excipients
• Nucleosomes
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• chelidonine

Topics

• Animals
• Apoptosis (drug effects)
• Benzophenanthridines (pharmacokinetics, pharmacology)
• Biological Availability
• Blotting, Western
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Central Nervous System Depressants (pharmacokinetics, pharmacology)
• Cytosol (metabolism)
• Drug Delivery Systems
• Drug Stability
• Excipients
• Lactic Acid
• Mice
• Microscopy, Atomic Force
• Microscopy, Fluorescence
• Mitochondria (metabolism)
• Nanoparticles
• Nucleosomes (drug effects, ultrastructure)
• Particle Size
• Polyglycolic Acid
• Polylactic Acid-Polyglycolic Acid Copolymer
• Signal Transduction (drug effects)
• Spectroscopy, Fourier Transform Infrared
• Static Electricity