Injectable thermosensitive PLGA-PEG-PLGA triblock copolymers-based hydrogels as carriers for interleukin-2.
Thermosensitive PLGA-PEG-PLGA triblock copolymers with the DL-lactide/glycolide molar ratio ranging from 6/1 to 15/1 were synthesized by bulk copolymerization of DL-lactide, glycolide and PEG1500. The resulting copolymers are soluble in water to form a freely flowing fluid at room temperature but become hydrogels at body temperature. The release of IL-2 from the copolymer-based hydrogel in the phosphate buffer (pH 7.2) was studied at 37 degrees C under agitation. IL-2 was released from the copolymer-based hydrogels over 20 days in vitro and the release rate decreased with increasing copolymer concentration. The change of DL-lactide/glycolide molar ratio in the PLGA block of the copolymer had little effect on the IL-2 release. The released IL-2 remained 57-90% of its original activity during the release period. To evaluate the anti-tumor effect of the IL-2 loaded copolymer, solutions were injected subcutaneously to H22 tumor-bearing mice. IL-2 loaded copolymer hydrogel for in vivo use showed good anti-tumor effect. These results indicate that the thermosensitive PLGA-PEG-PLGA triblock copolymers could be a promising platform for sustained delivery of IL-2.
Qiao
Mingxi
M
School of Pharmacy, Shenyang Pharmaceutical University, P.R. China. Qiaomingxi@163.com
Chen
Dawei
D
Hao
Tangna
T
Zhao
Xiuli
X
Hu
Haiyang
H
Ma
Xichen
X
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients; D005782:Gels; D020100:Hydrogels; D007267:Injections; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D008970:Molecular Weight; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D019999:Pharmaceutical Solutions; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005079:Excipients; D005782:Gels; D020100:Hydrogels; D007376:Interleukin-2; D019999:Pharmaceutical Solutions; D011994:Recombinant Proteins; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols