Bio-distribution and anti-tumor efficacy of PEG/PLA nano particles loaded doxorubicin.
As a more effective in vivo drug delivery system, several methods loading anti-cancer drugs to biodegradable and biocompatible nano-particles have been explored and developed. Supposedly due to the enhanced permeability and retention (EPR) effect, systemic administration of these nano-particles have been found to result in accumulation of nano-particles into solid tumors. In this study, we prepared nano-particles using polyethylene glycol (PEG)/poly-L-lactide (PLLA) diblock copolymer and loaded doxorubicin into these nano-particles (Nano-dox). The fabricated nano-particles exhibited sustained release kinetics of the drug in vitro. To follow the in vivo biodistribution of 200-350 nm sized nano-dox particles in tumor (syngenic renal cell adenocarcinoma: RENCA) bearing mouse, the carboxylfluorescenin diacetate succinimidyl ester (CFSE) was loaded into the nano-particles. Nano-dox accumulated preferentially in tumors; however, in terms of its anti-tumor efficacy, it did not show any marked benefits, compared to freely-administered doxorubicin. This result suggests the need to re-consider and evaluate what type of anti-cancer reagents we to be used in the ongoing efforts of coupling drug delivery system with tumor EPR effects.
Yu
J J
JJ
Medical Nano Element Development Center, Samsung Medical Center, Seoul, South Korea.
Lee
H A
HA
Kim
J H
JH
Kong
W H
WH
Kim
Y
Y
Cui
Z Y
ZY
Park
K G
KG
Kim
W S
WS
Lee
H G
HG
Seo
S W
SW
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D007773:Lactates / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D014018:Tissue Distribution; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D007773:Lactates; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D004317:Doxorubicin