| Summary: | In this work three DNA-chitosan nanoparticle formulations (Np), differing in the
molecular weight (MW; 150 kDa, 400 kDa, and 600 kDa) of the polysaccharide, were prepared
and administered by two different administration routes: the hydrodynamics-based procedure
and the intraduodenal injection. After the hydrodynamic injection, DNA-chitosan nanoparticles
were predominantly accumulated in the liver, where the transgene was expressed during at least
105 days. No signifi cant infl uence of MW was observed on the levels of luciferase expression.
The curves of bioluminescence versus time obtained using the charge-coupled device (CCD)
camera were described and divided in three phases: (i) the initial phase, (ii) the sustained
release step and (iii) the decline phase (promotor inactivation, immunological and physiological
processes). From these curves, which describe the transgene expression profi le, the behavior of
the different formulations as gene delivery systems was characterized. Therefore, the following
parameters such as Cmax (maximum level of detected bioluminescence), AUC (area under the
bioluminescence-time curve) and MET (mean time of the transgene expression) were calculated.
This approach offers the possibility of studying and comparing transgene expression kinetics
among a wide variety of gene delivery systems. Finally, the intraduodenal administration of
naked DNA permitted the gene transfer in a dose dependent manner quantifi able with the CCD
camera within 3 days. Nevertheless, the same administration procedure of the three formulations
did not improve the levels of transgene expression obtained with naked DNA. This fact could
be explained by the rapid physiological turn-over of enterocytes and by the ability of chitosan
nanoparticles to control the DNA release.
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