Structural analysis of nanoparticulate carriers for encapsulation of macromolecular drugs

Abstract

Recently developed macromolecular drugs display strong potential to cure diseases involving genetic components, e.g. Rheumatoid arthritis, diabetes, Alzheimer's disease, Huntington's disease, Duchenne muscular dystrophy, Retinitis pigmentosa, and several types of cancers. Bioavailability and enhanced drug specificity necessitate the preparation of efficient carrier systems for the macromolecular therapeutics. We employ synchrotron small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (Cryo-TEM) to study the nanostructure formation, macromolecular drug upload, and the topological transformations occurring upon complexation of supercoiled plasmid DNA (encoding for the therapeutic protein brain-derived neurotrophic factor, BDNF) with cationic lipid nanocarrier assemblies. Understanding of the liquid crystalline nanostructure formation (hexosomes, cubosomes, inverted hexagonal and intermediate mesophases, or onion-type complexes) enabling efficient delivery of new generation sequencing systems is expected to contribute to the progress in precision nanomedicine and the treatment of various severe diseases.