TY - JOUR
T1 - 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
AU - Paul, Avijit
AU - Das, Sreemanti
AU - Das, Jayeeta
AU - Samadder, Asmita
AU - Khuda-Bukhsh, Anisur Rahman
N1 - Funding Information:
This work was partially supported by a grant sanctioned to Prof. A.R. Khuda-Bukhsh, Department of Zoology, University of Kalyani , and partially by Boiron Laboratories, Lyon, France . We are thankful to Dr. Tarak Das Basu, and Mr. Arijit Kumar Chatterjee, Department of Biochemistry and Biophysics, Dr. Kumaresh Ghosh and Mr. Tanmoy Sarkar, Department of Chemistry, University of Kalyani, India, for permitting us to use their laboratory for conducting a part of the work.
PY - 2013/9/12
Y1 - 2013/9/12
N2 - 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±1.15nm) with good yield (86.34±1.91%), better encapsulation efficiency (82.6±0.574%), negative surface charge (-19.6±2.48mV) 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 (100mg/kg bw) in mice. Unlike FC, NC could permeate into brain tissue, indicating thereby NC's better potentials for use in therapeutic oncology.
AB - 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±1.15nm) with good yield (86.34±1.91%), better encapsulation efficiency (82.6±0.574%), negative surface charge (-19.6±2.48mV) 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 (100mg/kg bw) in mice. Unlike FC, NC could permeate into brain tissue, indicating thereby NC's better potentials for use in therapeutic oncology.
KW - Apoptosis
KW - Atomic force microscopy
KW - Bioavailability
KW - Chelidonine
KW - PLGA nanoparticles
KW - Signalling cascade
UR - http://www.scopus.com/inward/record.url?scp=84881021276&partnerID=8YFLogxK
U2 - 10.1016/j.toxlet.2013.07.006
DO - 10.1016/j.toxlet.2013.07.006
M3 - Article
C2 - 23850776
AN - SCOPUS:84881021276
SN - 0378-4274
VL - 222
SP - 10
EP - 22
JO - Toxicology Letters
JF - Toxicology Letters
IS - 1
ER -
