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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Available from: Minyong Li, Oct 03, 2015
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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.
    Nanoscale Research Letters 08/2014; 9(1):434. DOI:10.1186/1556-276X-9-434 · 2.78 Impact Factor
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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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    ABSTRACT: Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable poly (lactic acid)-poly(ethylene glycol)-poly(l-lysine) (PLA-PEG-PLL) copolymer, and explore its applicability and feasibility as a non-viral vector for gene transport. PLA-PEG-PLL was obtained by the ring-opening polymerization of Lys(Z)-NCA onto amine-terminated NH(2)-PEG-PLA, then acidolysis to remove benzyloxycarbonyl. The tri-block copolymer PLA-PEG-PLL combined the characters of cationic polymer PLL, PLA and PEG: the self-assembled nanoparticles (NPs) possessed a PEG loop structure to increase the stability, hydrophobic PLA segments as the core, and the primary ɛ-amine groups of lysine in PLL to electrostatically interact with negatively charged phosphate groups of DNA to deposit with the PLA core. The physicochemical properties (morphology, particle size and surface charge) and the biological properties (protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in HeLa and HepG2 cells) of the gene-loaded PLA-PEG-PLL nanoparticles (PLA-PEG-PLL NPs) were evaluated, respectively. Agarose gel electrophoresis assay confirmed that the PLA-PEG-PLL NPs could condense DNA thoroughly and protect DNA from nuclease degradation. Initial experiments showed that PLA-PEG-PLL NPs/DNA complexes exhibited almost no toxicity and higher gene expression (up to 21.64% in HepG2 cells and 31.63% in HeLa cells) than PEI/DNA complexes (14.01% and 24.22%). These results revealed that the biodegradable tri-block copolymer PLA-PEG-PLL might be a very attractive candidate as a non-viral vector and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo.
    International Journal of Molecular Sciences 12/2011; 12(2):1371-88. DOI:10.3390/ijms12021371 · 2.86 Impact Factor
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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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    ABSTRACT: Abstract Poly (lactic acid) (PLA) polymer has the promising applications in the biomedical field because of its biodegradability and safe elimination. In this study, we have explored the bio-application of new nanocomposites composed with PLA nanofibers and Au nanoparticles as the potential drug carrier for an efficient drug delivery in target cancer cells. The results demonstrated that the anticancer drug daunorubicin could be efficiently self-assembled on the surface of PLA/Au nanocomposites and the synergistic enhancement of PLA/Au nanocomposites conjugated with daunorubicin into drug-sensitive K562 and drug-resistant leukemia K562/AO2 cells could be obviously observed by MTT assay and confocal fluorescence microscopy studies. These observations suggest that the new nanocomposites could readily induce daunorubicin to accumulate and uptake in target leukemia cells and increase the drug's cytotoxicity. Especially, the PLA/Au nanocomposites could significantly facilitate the cellular drug absorbtion of daunorubicin into drug-resistant K562/AO2 cells and efficiently inhibit the cancer cell proliferation. This raised the possibility to utilize the PLA/Au nanocomposites as a new effective additive agent to inhibit the drug resistance and thus as a novel strategy to sensitively track the respective cancer cells.
    Nanoscale Research Letters 01/2011; 6(1). DOI:10.1007/s11671-010-9762-3 · 2.78 Impact Factor
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