Addition of pluronics® to reducible disulfide-bond-containing Pluronic®-PEI-SS specifically enhances circulation time in vivo and transfection efficiency in vitro.
To improve the circulation time and transfection efficiency of the polyplexes used in gene delivery, a series of Pluronic®/Pluronic®F127-PEI-SS/pDNA complexes (PFPS/pDNA), based on the addition of different kinds of Pluronics® to the reducible disulfide-bonds-containing Pluronic®F127-PEI-SS/pDNA (FPS/pDNA) polyplexes, was prepared and evaluated in Bcap and Hela cells in vitro and in vivo. The addition of Pluronics® with molecular weights and hydrophilic-lipophilic balance (HLBs) different from that in the FPS/pDNA complex resulted in five PFPS(1-5)/pDNA complexes, and the correlation between the structure of the free Pluronic® and the properties of the PFPS/pDNA complexes was investigated. The addition of Pluronics® resulted in slightly larger or same-sized nanoparticles of PFPS/pDNA at a constant N/P ratio. The PFPS copolymer displayed strong stability against DNase I digestion and serum degradation. PFPS-4 containing added Pluronic® L35, with an intermediate HLB of 19, showed a much higher transfection efficiency and less cytotoxicity than FPS or PEI-25 kDa in vitro. PFPS-4 also exhibited a considerably longer blood circulation time than FPS or PEI-25 kDa in vivo in mice, indicating that the addition of an intermediate Pluronic® can enhance the transfection efficiency of gene delivery systems.
State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Institute of Biochemical Engineering and Environmental Technology, Lanzhou University, Lanzhou, 730000, China.
Zhenzhen
Z
Chen
Lifen
L
Zhang
Yanfeng
Y
Li
D000818:Animals; D004247:DNA / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010957:Plasmids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011409:Propylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014162:Transfection / Q000379:methods*
D011409:Propylene Glycols; D011092:Polyethylene Glycols; D004247:DNA
Pluronic; biodegradation; enhancement; stability