Injectable block copolymer hydrogels for sustained release of a PEGylated drug.
The paper employs the spontaneous physical gelling property of a biodegradable polymer in water to prepare an injectable sustained release carrier for a PEGylated drug. A series of thermogelling PLGA-PEG-PLGA triblock copolymers were synthesized. The PEGylated camptothecin (CPT) was also prepared and employed as the model of a PEGylated drug, and the solubility of this hydrophobic drug was significantly enhanced to over 150mg/mL. The model drug was completely entrapped into the polymeric hydrogel, and the sustained release lasted for 1 month. The mechanism of the sustained release was diffusion-controlled at the first stage and then was the combination of diffusion and degradation at the late stage. In vivo anti-tumor tests in mice further confirmed the efficacy of the model PEGylated drug released from the hydrogel. This work also revealed the specificity of the PEGylated drug in such a kind of carrier systems by decreasing the critical gelling temperature and increasing the viscosity of the sol. Due to the very convenient drug formulation and highly tunable release rate, an injectable carrier platform for PEGylated drugs is thus set up.
Yu
Lin
L
Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
Chang
Guang Tao
GT
Zhang
Huan
H
Ding
Jian Dong
JD
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D002166:Camptothecin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006016:Glycolates / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D007279:Injections, Subcutaneous; D007700:Kinetics; D019344:Lactic Acid; D051379:Mice; D008815:Mice, Inbred Strains; D046529:Microscopy, Electron, Transmission; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature; D014783:Viscosity