Abstract
OBJECTIVE To prepare nonviral vector of solid lipid nanoparticles carrying protamine-pDNA complex(PD-SLN),to develop a Multifunctional Envelope-type Nano Device(MEND) structure,in which the core of a plasmid DNA,condensed by a polycation,is encapsulated by a lipid envelope,then the nanoparticles' characteristics,the protection ability and the DNA release property in vitro were evaluated.METHODS PD-SLN was prepared by emulsion solvent diffusion method and double emulsion solvent evaporation method,respectively.The morphology of PD-SLN was observed by transmission electron microscopy.The particle sizes,polydispersity,Zeta potential were measured by nanoparticle size analyser.Encapsulating efficiency of pDNA was determined by fluorescence spectrometer.The protection of complex and PD-SLN from intensive force and nuclease degradation were evaluate by agarose gel electrophoresis,respectively.The method of two-compartment diffusion was employed to investigate the releasing character of DNA from PD-SLN.RESULTS The morphology of PD-SLN were approximately spherical.The average partic1e sizes of PD-SLN obtained by the two different methods were(231±13.7) and(627±22.9)nm,respectively.The Zeta potentials were(-17.8±3.2) and(-25.2±2.7)mV,respectively.Encapsulating efficiencies were(41.5±3.62)% and(56.5±5.28)%,respectively.The intensive agitation and nuclease degradation test results confirmed that the pDNA was protected considerably.PD-SLN Maintained sustained-release of pDNA for several days in vitro.CONCLUSION PD-SLN could be prepared easily with small particle sizes,excellent sustained-release activity,and protection of pDNA.In vitro studies have showed that PD-SLN could be a promising device,which has the potential to make in vivo cancer gene therapy achievable.
Key words
protamine-pDNA complex /
solid lipid nanoparticles /
Multifunctional Envelope-type Nano Device /
non-viral gene vector
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YE Jie-sheng;ZHNG N;M Chun-hong;HUNG Gui-hu;LUN Fng.
Preliminary Studies on Protamine-pDNA Complex Loaded Solid Lipid Nanoparticles [J]. Chinese Pharmaceutical Journal, 2007, 42(21): 1644-1648
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