Preparation and Characterization of Cationic PLA-PEG Nanoparticles for Delivery of Plasmid DNA

School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, 250012 Ji-nan, China.
Nanoscale Research Letters (Impact Factor: 2.78). 09/2009; 4(9):982-992. DOI: 10.1007/s11671-009-9345-3
Source: PubMed


The purpose of the present work was to formulate and evaluate cationic poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) nanoparticles as novel non-viral gene delivery nano-device. Cationic PLA-PEG nanoparticles were prepared by nanoprecipitation method. The gene loaded nanoparticles were obtained by incubating the report gene pEGFP with cationic PLA-PEG nanoparticles. The physicochemical properties (e.g., morphology, particle size, surface charge, DNA binding efficiency) and biological properties (e.g., integrity of the released DNA, protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in Hela cells) of the gene loaded PLA-PEG nanoparticles were evaluated, respectively. The obtained cationic PLA-PEG nanoparticles and gene loaded nanoparticles were both spherical in shape with average particle size of 89.7 and 128.9 nm, polydispersity index of 0.185 and 0.161, zeta potentials of +28.9 and +16.8 mV, respectively. The obtained cationic PLA-PEG nanoparticles with high binding efficiency (>95%) could protect the loaded DNA from the degradation by nuclease and plasma. The nanoparticles displayed sustained-release properties in vitro and the released DNA maintained its structural and functional integrity. It also showed lower cytotoxicity than Lipofectamine 2000 and could successfully transfect gene into Hela cells even in presence of serum. It could be concluded that the established gene loaded cationic PLA-PEG nanoparticles with excellent properties were promising non-viral nano-device, which had potential to make cancer gene therapy achievable.

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    • "Incorporation of long-chain PEG molecules on the surface of NPs is of significant importance as they can not only protect NPs from degradation by enzymes during in vivo circulation [18], increasing the stability of NPs and prolonging circulation time [19], but also allow the inclusion of reactive groups in PEG molecules to offer flexible conjugation of various antigens [20]. For targeted delivery purposes, antibodies or affinity ligands against receptors of target cells or tissues may be conjugated to the surface of NPs via PEG chains [21,22]. "
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    ABSTRACT: Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC.
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    • "To protect the DNA cargo, one approach in the application of PLGA NPs for nucleic acid delivery uses adsorption of the anionic DNA molecules onto cationic NPs by the use of cationic surfactants, like cetyltrimethyl ammonium bromide (CTAB), and 3,2′-dimethyl-4-aminobiphenyl (DMAB) in the formulations [15]. In our previous studies, Zou et al. also investigated how gene loaded cationic PLA-PEG NPs modified by CTAB could successfully transfect a gene into HeLa cells even in the presence of serum [16]. However, there is no doubt that introduction of cationic surfactants would generate cytotoxicity. "
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    • "Au nanoparticles were also applied as a potential carrier or protective container for biologically active agents [8]. With the characteristics of biocompatibility, biodegradability and absorbability, some polymers have been widely used in medical research such as DNA binding delivery with PLA/PEG nanoparticles, poorly soluble Ethaselen's delivery with mPEG-PLA copolymers, prostheses for tissue replacements, supporting surgical operation and artificial organs for temporary or permanent assistance [17-19]. Some biocompatible polymer can also act as drug carriers by controlling the release rate of the loaded drug [20-23]. "
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