Biodegradable nanoparticles modified by branched polyethylenimine for plasmid DNA delivery

Sejin Son; Won Jong Kim

doi:10.1016/j.biomaterials.2009.09.024

Biodegradable nanoparticles modified by branched polyethylenimine for plasmid DNA delivery

Sejin Son, Won Jong Kim

Pohang University of Science and Technology

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

Abstract

The main objective of this work is to build a comparative account of two PLGA nanoparticle (NP)-based gene delivery systems namely, plasmid DNA (pDNA) encapsulated PLGA NPs (PLGA-E) and surface adsorbed pDNA on PLGA-BPEI NPs (PLGA-BPEI), with respect to the extent of internalization and intracellular release of pDNA. Several formulations have also been evaluated systematically for determination of the optimal transfection efficiency. The zeta-potential, particle size measurements and DNase I protection assay established the importance of the BPEI chain length in regulating the effective loading and condensation of pDNA with PLGA-BPEI NPs and pDNA protection ability of PLGA-BPEI NPs. The colloidal stability of these formulations was also investigated as a function of serum concentration. The in vitro release of pDNA from both kind of formulations was studied at pH 7.4 and pH 5.0 by comparing the kinetics of pH-triggered release of pDNA from PLGA-BPEI-25K(5) and PLGA-E. In vitro time-dependent gene transfection efficiencies were studied in presence as well as in absence of serum for NIH3T3 and HEK293 cells. The cell viability and intracellular localization were also investigated using MTT assay and confocal microscopy study, respectively.

Original language	English
Pages (from-to)	133-143
Number of pages	11
Journal	Biomaterials
Volume	31
Issue number	1
DOIs	https://doi.org/10.1016/j.biomaterials.2009.09.024
State	Published - Jan 2010
Externally published	Yes

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (20090068098), and by a grant from the Fundamental R&D Program for Core Technology of Materials funded by the Ministry of Knowledge Economy, Republic of Korea, and POSCO Research Fund. We thank Prof. Sungjee Kim for assistance in the particle size and zeta-potential measurement studies.

Keywords

Biodegradation
Cell toxicity
Gene therapy
Nanoparticle (NP)
Poly (lactic-co-glycolic acid) (PLGA)

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10.1016/j.biomaterials.2009.09.024

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title = "Biodegradable nanoparticles modified by branched polyethylenimine for plasmid DNA delivery",

abstract = "The main objective of this work is to build a comparative account of two PLGA nanoparticle (NP)-based gene delivery systems namely, plasmid DNA (pDNA) encapsulated PLGA NPs (PLGA-E) and surface adsorbed pDNA on PLGA-BPEI NPs (PLGA-BPEI), with respect to the extent of internalization and intracellular release of pDNA. Several formulations have also been evaluated systematically for determination of the optimal transfection efficiency. The zeta-potential, particle size measurements and DNase I protection assay established the importance of the BPEI chain length in regulating the effective loading and condensation of pDNA with PLGA-BPEI NPs and pDNA protection ability of PLGA-BPEI NPs. The colloidal stability of these formulations was also investigated as a function of serum concentration. The in vitro release of pDNA from both kind of formulations was studied at pH 7.4 and pH 5.0 by comparing the kinetics of pH-triggered release of pDNA from PLGA-BPEI-25K(5) and PLGA-E. In vitro time-dependent gene transfection efficiencies were studied in presence as well as in absence of serum for NIH3T3 and HEK293 cells. The cell viability and intracellular localization were also investigated using MTT assay and confocal microscopy study, respectively.",

keywords = "Biodegradation, Cell toxicity, Gene therapy, Nanoparticle (NP), Poly (lactic-co-glycolic acid) (PLGA)",

author = "Sejin Son and Kim, {Won Jong}",

note = "Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (20090068098), and by a grant from the Fundamental R&D Program for Core Technology of Materials funded by the Ministry of Knowledge Economy, Republic of Korea, and POSCO Research Fund. We thank Prof. Sungjee Kim for assistance in the particle size and zeta-potential measurement studies. ",

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AB - The main objective of this work is to build a comparative account of two PLGA nanoparticle (NP)-based gene delivery systems namely, plasmid DNA (pDNA) encapsulated PLGA NPs (PLGA-E) and surface adsorbed pDNA on PLGA-BPEI NPs (PLGA-BPEI), with respect to the extent of internalization and intracellular release of pDNA. Several formulations have also been evaluated systematically for determination of the optimal transfection efficiency. The zeta-potential, particle size measurements and DNase I protection assay established the importance of the BPEI chain length in regulating the effective loading and condensation of pDNA with PLGA-BPEI NPs and pDNA protection ability of PLGA-BPEI NPs. The colloidal stability of these formulations was also investigated as a function of serum concentration. The in vitro release of pDNA from both kind of formulations was studied at pH 7.4 and pH 5.0 by comparing the kinetics of pH-triggered release of pDNA from PLGA-BPEI-25K(5) and PLGA-E. In vitro time-dependent gene transfection efficiencies were studied in presence as well as in absence of serum for NIH3T3 and HEK293 cells. The cell viability and intracellular localization were also investigated using MTT assay and confocal microscopy study, respectively.

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KW - Cell toxicity

KW - Gene therapy

KW - Nanoparticle (NP)

KW - Poly (lactic-co-glycolic acid) (PLGA)

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Biodegradable nanoparticles modified by branched polyethylenimine for plasmid DNA delivery

Abstract

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Keywords

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