Magnetic Nanoparticles of Chitosan for Targeted Delivery System of Plasmids to the Lungs

Abstract

One of the major problems of gene therapy is the efficient, specific, and targeted delivery as well as the safety of the materials used in such systems. The specific targeted delivery of genes to the lung offers the possibility to treat a variety of specific diseases. We developed chitosan nanoparticles with the plasmid pCEM-Luc, which contains a promoter activated by magnetic field. Nanoparticles of 200–250 nm obtained by ionic gelation with a 99% retention rate were transfected in B16F10 cells andin vivoin the lungs of Balb/c mice by intratracheal administration. We observed that an external magnetic field increased the expression of the luciferase reporter gene in B16F10 cells transfected with magnetic nanoparticles and in homogenized lungs of mice which determined differences in levels of expression between different regions of the lungs (apical or distal and left or right). The highest levels of luciferase activity were observed in the apical left region. The magnetic nanoparticles prove an efficient delivery system toin vitrotransfection of cells and lung tissue.

Systemic delivery and activation of the <em>TRAIL</em> gene in lungs, with magnetic nanoparticles of chitosan controlled by an external magnetic field

“…7 The chitosan-DNA NPs were prepared at an nitrogen:phosphate ratio of 1:60 with a ζ-potential of -25 mV, which resulted in optimum NPs of 200-250 nm (Figure 3), an appropriate size for transfection in vitro and in vivo. The spherical and compact morphology was a consequence of the chitosan-controlled gelation promoted by TPP.…”

“…The administration of 50 µg of naked plasmid produce an adequate expression of transgene in the lungs of mice. 7 It is possible that the level of apoptosis occurring in these appropriate conditions improved mouse survival. On the other hand, when the same amount of plasmid (50 µg) was administered in the chitosan MNPs, it produced a high level of apoptosis in the lung, as demonstrated in the TUNEL assay.…”

“…4 Different approaches for the delivery of genes to the lungs, such as intravenous (IV) injection and nasal or intratracheal instillation, have been reported. [5][6][7] correspondence: Juan M alcocergonzález laboratorio de Inmunología y Virología, Facultad de ciencias Biológicas, Universidad autónoma de Nuevo león, avenida Pedro de alba, san Nicolás de los garza, Nuevo león 66450, Mexico Tel +52 83 294 000 ext 5112 email juan.alcocerg@uanl.mx…”

Magnetofection Enhances Lentiviral-Mediated Transduction of Airway Epithelial Cells through Extracellular and Cellular Barriers

“…The concern arose that this could limit the application of the magnetofection technique in vivo as a result of the thickness of tissues that could oppose the magnetic forces at the level of the respiratory epithelium, a setting that could necessitate more than 20 min of incubation time. However, it must be said that in vivo experiments in mice have demonstrated the feasibility of magnetofection to the lung, studied either withplasmid DNA (pDNA) deposition [34] or luciferase expression [35], when an external magnetic field was applied externally on the thorax (up to 72 h [35]). Interestingly, in the present study, magnetofection increased the transduction levels in the presence of the sol phase obtained from CF sputum, a phenomenon which was not reproducible in the absence of a magnetic field (Figure 3).…”