Sub-100 nm chitosan-triphosphate-DNA nanoparticles for delivery of DNA vaccines

Intramuscular delivery is one of the main route for DNA vaccines administration. However, it requires large amounts of the DNA administered and external stimulation to encourage the internalization of the DNA. In this work we consider routes for less invasive administration route, and develop drug delivery systems (DDS) for intranasal administration. Chitosan polyplexes using sodium tripolyphosphate (TPP) as a crosslinker were prepared using the ionic gelation method. Our method allowed preparation of nanoparticles with the size bellow 50nm that is at least two times lower than previously reported. Moreover, despite small size, we obtained DNA encapsulation efficiencies about 70%. Parameters that may affect the encapsulation efficiency were investigated, including different chitosan-TPP ratios and concentrations of DNA. We found that encapsulation efficiency of DNA inside the particles increases with the increasing TPP-chitosan ratio. Moreover, increasing the DNA concentration also leads to a higher encapsulation efficiency. Small (<50nm) chitosan nanoparticles hold enormous potential as DNA carriers through physiological barriers and subsequent internalization.