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Gene-therapy Inspired Polycation Coating for Protection of DNA Origami Nanostructures
Published on: January 19, 2019
Drying of a plasmid containing formulation: chitosan as a protecting agent
Nasir Mohajel1, Abdolhossein R Najafabadi, Kayhan Azadmanesh
1Aerosol Research Laboratory, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. gilani@sina.tums.ac.ir.
Summary
Low molecular weight chitosan (LMWC) effectively preserves gene delivery vector transfection efficiency and DNA structure after spray-drying and freeze-drying. These stabilization methods maintain nanocomplex integrity and function, even with common excipients like leucine.
Area of Science:
- Biomaterials Science
- Gene Therapy Delivery Systems
- Polymer Chemistry
Background:
- Developing efficient gene delivery systems requires methods to extend their shelf-life.
- Chitosan offers a non-toxic, biocompatible, and accessible option for gene delivery carriers.
Purpose of the Study:
- To evaluate chitosan's capability in maintaining transfection efficiency during spray-drying and modified freeze-drying.
- To assess the protective effects of chitosan on DNA structure and nanocomplex integrity post-drying.
Main Methods:
- Chitosan's molecular weight was reduced to create low molecular weight chitosan (LMWC).
- LMWC was complexed with plasmid DNA (pDNA) to form nanocomplexes.
- Nanocomplex suspensions were processed using spray-drying or a modified freeze-drying technique with lactose and leucine excipients.
Main Results:
- Size distribution of most processed nanocomplexes remained similar to fresh ones.
- LMWC protected plasmid DNA structure in both drying processes, though spray-drying showed higher degradation at low N/P ratios.
- Transfection efficiency was preserved similarly by both methods, even at lower N/P ratios.
Conclusions:
- Low molecular weight chitosan (LMWC) effectively protects DNA structure and transfection efficiency during spray-drying and freeze-drying.
- The presence of leucine did not significantly impact the properties of the processed nanocomplexes.
- Both drying techniques are viable for stabilizing chitosan-based gene delivery vectors.

