Abstract
In this work, we propose chitosan (CS)-based nanocapsules (NCs) for pulmonary gene delivery. Hyaluronic acid (HA) was incorporated in the NCs composition (HA/CS NCs) aiming to promote gene transfection in the lung epithelium. NCs were loaded with a model plasmid (pCMV-βGal) to easily evaluate their transfection capacity. The plasmid encapsulation efficiencies were of approx. 90%. To facilitate their administration to the lungs, the plasmid-loaded NCs were microencapsulated in mannitol (Ma) microspheres (MS) using a simple spray-drying technique, obtaining dry powders of adequate properties. In vivo, the MS reached the deep lung, where the plasmid-loaded CS-based NCs were released and transfected the alveolar cells more homogeneously than the control formulation of plasmid directly microencapsulated in Ma MS. The HA-containing formulation achieved the highest transfection efficiency, in a more extended area and more homogeneously distributed than the rest of tested formulations. The new micro-nanostructured platform proposed in this work represents an efficient strategy for the delivery of genetic material to the lung, with great potential for the treatment of genetic lung diseases.
Highlights
Gene therapy offers hope of treatment for rare and other serious diseases that currently have no established effective treatments
The NCs were loaded with a model plasmid aimed to demonstrate their in vivo transfection potential
Various CS-based NCs formulations (CS NCs, Hyaluronic acid (HA)/CS NCs, pCMV-βGal-CS NCs and pCMV-βGal-HA/CS NCs) were prepared using the procedure described in the Methodology
Summary
Gene therapy offers hope of treatment for rare and other serious diseases that currently have no established effective treatments. Skvortsov et al described in 2013 the transcriptome of Mycobacterium tuberculosis in infected mouse lungs and identified those genes whose expression were increased with the progression of the infection [5]. These virulence genes are a good target for applying gene therapy, by the administration of siRNAs capable of interfering in their expression. Parallel to the identification of the mechanisms involved in diseases susceptible to be treated with
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