A thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of docetaxel.
The aim of this study was to investigate the suitability of poly-(d,l-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymer as a matrix material for a sustained-release system for docetaxel (DTX). The copolymers were synthesized by ring-opening polymerization reaction and characterized by (1)H-NMR and gel permeation chromatography. The DTX-loaded formulations were prepared, characterized. And the antitumor efficacy and the pharmacokinetics of DTX-loaded copolymer on A-549 lung tumor-bearing BALB/cA mice were investigated. The results showed that DTX-loaded copolymer highly increased the solubility of DTX by more than 3000-fold. And copolymer concentration as well as drug loading level exerted appreciable influence on the drug release behavior. Further, the pharmacokinetic test showed that DTX-loaded copolymer could be with the sustained-release nature for over 3 weeks, which correlated well with the in vitro release. Additionally, one intratumoral injection of the thermo-sensitive hydrogel containing DTX was comparable to three intravenous injections of DTX injection in inhibiting the tumor growth in A-549 lung tumor-bearing BALB/cA mice with a less toxic manner. PLGA-PEG-PLGA could thus provide a promising alternate locally delivered vehicle for DTX to achieve prolonged exposure having greater efficacy in inhibiting tumor growth with lower toxicity.
Gao
Yuan
Y
Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China.
Ren
Fuzheng
F
Ding
Baoyue
B
Sun
Ningyun
N
Liu
Xiang
X
Ding
Xueying
X
Gao
Shen
S
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000077143:Docetaxel; D020100:Hydrogels; D020128:Inhibitory Concentration 50; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D033362:Powder Diffraction; D012212:Rheology; D012995:Solubility; D043823:Taxoids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D014961:X-Ray Diffraction
D000972:Antineoplastic Agents, Phytogenic; D020100:Hydrogels; D008823:Micelles; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols