Preparation of DHAQ-loaded mPEG-PLGA-mPEG nanoparticles and evaluation of drug release behaviors in vitro/in vivo.
This study describes the preparation and the evaluation of biodegradation monomethoxy (polyethylene glycol)-poly (lactide-co-glycolide)-monomethoxy (polyethyleneglycol) (mPEG-PLGA-mPEG, PELGE) nanoparticles (PELGE-NP) containing mitoxantrone (DHAQ) as a model drug. PELGE copolymers with various molar ratios of lactic to glycolic acid and different molecular weights and various content mPEG were synthesized by ring-opening polymerization. mPEG with weight-average molecular weight (Mw) 2,000 or 5,000 was introduced as a hydrophilic segment into a hydrophobic PLGA. A double emulsion method with dextran70 as stabilizer in the external aqueous phase was used to prepare the nanoparticles. The drug entrapment efficiencies were more than 80% and the mean diameters of the nanoparticles were less than 200 nm. Various PELGE was studied as biodegradable drug carriers and there in vitro/in vivo release profiles were examined. It was found that drug loading, polymer molecular weight, copolymer composition and end group modifications were critical factors affecting the in vitro/in vivo release properties. The amount of drug released increased as the mPEG contents increased and the molar ratios of lactic acid decreased in vitro. The intravenous (i.v.) administration of mPEG-PLGA-mPEG nanoparticles of DHAQ in mice resulted in prolonged DHAQ residence in systemic blood circulation compared to the intravenous administration of PLGA nanoparticles.
Duan
Yourong
Y
Shanghai Cancer Institute, Cancer Institute of Shanghai JiaoTong University, Shanghai 200032, China. yrduan@dhu.edu.cn
Sun
Xun
X
Gong
Tao
T
Wang
Qi
Q
Zhang
Zhirong
Z
D000818:Animals; D001673:Biodegradation, Environmental; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D051379:Mice; D008942:Mitoxantrone / Q000493:pharmacokinetics*; D008970:Molecular Weight; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D036103:Nanotechnology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D008942:Mitoxantrone