Abstract
Purpose. A tri-block copolymer of PLGA-PEG-PLGA was used as an excipient to enhance the gene transfection efficiency of various cationic polymeric carriers.
Methods. Luciferase plasmid DNA was complexed with polyethylenimine for gene transfection. Various concentrations of PLGA-PEG-PLGA copolymer up to 0.5% were added in the transfection medium to explore whether the copolymer increased the level of gene expression. Pluronic F68 was used as a control. Various polyplexes and different cell lines were used to verify the effect of the triblock copolymer on gene transfection. The cellular uptake extent of radiolabeled plasmid was quantitatively determined as a function of PLGA-PEG-PLGA concentration.
Results. PLGA-PEG-PLGA copolymer significantly enhanced gene transfection efficiency at a concentration as low as 0.25% (w/v), which was more effective than Pluronic F68 at the same concentration range. The additive effect of the triblock copolymer in the transfection medium was clearly observed for various cationic polyplexes and cell lines, although the gene expression extents largely depended on polymers and cell lines used. Five- to 10-fold increment of gene transfection levels were attained in the presence of the PLGA-PEG-PLGA tri-block copolymer. The enhanced gene transfection efficiency was attributed to the increased cellular uptake of PEI/DNA complexes in the presence of the PLGA-PEG-PLGA tri-block copolymer.
Conclusions. Biodegradable PLGA-PEG-PLGA tri-block copolymer that facilitates the endocytic process can be used as a novel additive in non-viral gene transfection.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
F. D. Ledley. Nonviral gene therapy: the promise of genes as pharmaceutical products. Hum. Gene Ther. 6:1129-1144 (1995).
A. Rolland and P. Felgner. (eds). Non-viral gene delivery systems. Adv. Drug Del. Rev. 30:1-227 (1998).
S. C. De Smedt, J. Demeester, and W. E. Hennink. Cation polymer based gene delivery systems. Pharm. Res. 17:113-126 (2000).
O. Boussif, F. Lezoualc'h, M. A, Zanta, M. D. Mergny, D. Scheman, B. Demeneix, and J. P. Behr. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc. Natl. Acad. Sci. USA 92:7297-7303 (1995).
J. H. Jeong, S. H. Song, D. W. Lim, H. Lee, and T. G. Park. DNA Transfection Using Linear Poly(ethylenimine) Prepared by Controlled Acid Hydrolysis of Poly(2-ethyl-2-oxazoline). J. Control. Release 73:391-399 (2001).
R. J. Mumper, J. G. Duguid, K. Anwer, M. K. Barron, H. Nitta, and A. P. Rolland. Polyvinyl derivatives as novel interactive polymers for controlled gene delivery to muscle. Pharm. Res. 13:701-709 (1996).
P. L. Felgner, T. R. Gader, M. Holm, R. Roman, H. W. Chan, M. Wenz, J. P. Nerthrop, G. M. Ringold, and M. Danielsen. Lipofection: a highly efficient, lipid-mediated DNA transfection procedure. Proc. Natl. Acad. Sci. USA 84:7412-7417 (1987).
S. Han, R. I. Mahato, and S. W. Kim. Water-soluble lipopolymer for gene delivery. Bioconjug. Chem. 12:337-345 (2001).
Y. H. Choi, F. Liu, J. S. Park, and S. W. Kim. Lactose-poly(ethylene glycol)-grafted poly-L-lysine as hepatoma cell targeted gene carrier. Bioconjug. Chem. 9:708-718 (1998).
H. Lee, J. H. Jeong, and T. G. Park. PEG grafted polylysine with fusogenic peptide for gene delivery: high transfection efficiency with low cytotoxicity. J. Control. Release 79:283-291 (2002).
H. Lee, J. H. Jeong, and T. G. Park. A New Gene Delivery Formulation of polyethyleneimine/DNA complexes coated with PEG conjugated fusogenic peptide. J. Control. Release 76:138-192 (2001).
P. Lemieux, N. Guerin, G. Paradis, R. Proulx, L. Chistyakova, A. Kabanov, and V. Alakhov. A combination of poloxamers increases gene expression of plasmid DNA in skeletal muscle. Gene Ther. 7:986-991 (2000).
J. Liaw, S.-F. Chang, and F.-C. Hsiao. In vivo gene delivery into ocular tissues by eye drops of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles. Gene Ther. 8:999-1004 (2001).
H.-K. Nguyen, P. Lemieux, S. V. Vinogradov, C. L. Gebhart, N. Guerin, G. Paradis, T. K. Bronich, V. Y. Alakhov, and A. V. Kabanov. Evaluation of polyether-polyethylenimine graft copolymers as gene transfer agents. Gene Ther. 7:986-991 (2000).
I. Astafieva, I. Maksimova, E. Lukanidin, V. Alakhov, and A. Kabanov. Enhancement of the polycation-mediated uptake and cell transfection with Pluronic P85 block co-polymer. FEBS Lett. 389:278-280 (1996).
C. W. Cho, Y. S. Cho, H. K. Lee, Y. I. Yeom, S. N. Park, and D. Y. Yoon. Improvement of receptor-mediated gene delivery to HepG2 cells using an amphiphilic gelling agent. Biotechnol. Appl. Biochem. 32:21-26 (2000).
B. Jeong, Y. H. Bae, D. S. Lee, and S. W. Kim. Biodegradable block copolymers as injectable drug delivery systems. Nature 388:860-862 (1997).
F. Liu, J. Yang, L. Huang, and D. Liu. Effect of non-ionic surfactants on the formation of DNA/emulsion complexes and emulsion-mediated gene transfer. Pharm. Res. 13:1642-1646 (1996).
J. Hartikka, L. Sukhu, C. Buchner, D. Hazard, V. Bozoukova, M. Margalith, W. K. Nishioka, C. J. Wheeler, M. Manthorp, and M. Sawdey. Electroporation-facilitated delivery of plasmid DNA in skeletal muscle: plasmid dependence of muscle damage and effect of poloxamer 188. Mol. Ther. 4:407-415 (2001).
M. Y. Kozlov, N. S. Melik-Nubarov, E. V. Batrakova, and A. V. Kabanov. Relationship between Pluronic block copolymer structure, critical micellization concentration and partitioning coefficients of low molecular mass solutes. Macromolecules 33:3305-3313 (2000).
A. V. Kabanov, P. Lemieux, S. Vinogradov, and V. Alakhov. Pluronic® block copolymers: novel functional molecules for gene therapy. Adv. Drug Del. Rev. 54:223-233 (2002).
V. Alakhov, E. Moskaleva, E. V. Batrakova, and A. V. Kabanov. Hypersensitization of multidrug resistant human ovarian carcinoma cells by Pluronic P85 block copolymer. Bioconjug. Chem. 7:209-216 (1995).
V. Alakhov and A. V. Kabanov. Block copolymeric biotransport carriers as versatile vehicles for drug delivery. Exp. Op. Invest. Drugs 7:1453-1473 (1998).
G. M. Zentner, R. Rathi, C. Shih, J. C. McRea, M.-H. Seo, H. Oh, B. G. Rhee, J. Mestecky, Z. Moldoveanu, M. Morgan, and S. Weitman. Biodegradable block copolymers for delivery of proteins and water-insoluble drugs. J. Control Release. 72:203-215 (2001).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jeong, J.H., Kim, S.W. & Park, T.G. Biodegradable Triblock Copolymer of PLGA-PEG-PLGA Enhances Gene Transfection Efficiency. Pharm Res 21, 50–54 (2004). https://doi.org/10.1023/B:PHAM.0000012151.05441.bf
Issue Date:
DOI: https://doi.org/10.1023/B:PHAM.0000012151.05441.bf