A preliminary study on MeO-PEG-PLGA-PEG-OMe nanoparticles as intravenous carriers.
To develop an intravenous nanoparticle delivery system for a cancer drug (i.e., DHAQ, mitoxantrone), the synthesis of a biodegradable polyester polymer with hydrophilic polyethylene glycol chains, preparation of DHAQ-loaded nanoparticles from such polymer and biodistribution of the drug-loaded particles were investigated in this article. Biodegradable monomethoxy poly(ethylene glycol)-poly (lactide-co-glycolide)-monomethoxy poly(ethylene glycol) (MeO-PEG-PLGA-PEG-OMe, PELGE) copolymers were synthesized by ring-opening polymerization as the drug carriers. A double emulsion method with dextran-70 as an emulsifier was employed to prepare the nanoparticles. DHAQ-PELGE nanoparticles and free DHAQ were employed for the in vivo biodistribution studies after intravenous administration through the tail veins in mice. At various time intervals, the mice were sacrificed and several organs and tissues harvested, including hearts, livers, spleens, lungs, kidneys, and blood. The DHAQ concentrations in the collected tissues and plasmas were determined using high performance liquid chromatography. The DHAQ concentrations in mice plasmas in the experimental groups were significantly higher than those in the control group and 3.72% of total administrations dosages (TAD) of these particles with DHAQ remained in circulation even 96 h after intravenous injection. Compared with the free DHAQ, DHAQ-loaded PELGE nanoparticles had longer circulation properties. Further research should be done for intravenous injection of this material as drug carriers.
Duan
Yourong
Y
Cancer Institute of Shanghai Jiao Tong University, Shanghai 200032, China.
Xu
Jinping
J
Lin
Yunzhu
Y
Yu
Hui
H
Gong
Tao
T
Li
Yaogang
Y
Zhang
Zhirong
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D051379:Mice; D008942:Mitoxantrone / Q000737:chemistry / Q000493:pharmacokinetics; D015394:Molecular Structure; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; C525451:methylpoly(ethylene glycol)-oly(lactic acid-co-glycolic acid)-poly(ethylene glycol); D011092:Polyethylene Glycols; D008942:Mitoxantrone