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Chitosan as a nonviral gene delivery system. Structure-property relationships and characteristics compared with polyethylenimine in vitro and after lung administration in vivo
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
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2001 (English)In: Gene Therapy, ISSN 0969-7128, E-ISSN 1476-5462, Vol. 8, no 14, 1108-1121 p.Article in journal (Refereed) Published
Abstract [en]

Chitosan is a natural cationic linear polymer that has recently emerged as an alternative nonviral gene delivery system. We have established the relationships between the structure and the properties of chitosan-pDNA polyplexes in vitro. Further, we have compared polyplexes of ultrapure chitosan (UPC) of preferred molecular structure with those of optimised polyethylenimine (PEI) polyplexes in vitro and after intratracheal administration to mice in vivo. Chitosans in which over two out of three monomer units carried a primary amino group formed stable colloidal polyplexes with pDNA. Optimized UPC and PEI polyplexes protected the pDNA from serum degradation to approximately the same degree, and they gave a comparable maximal transgene expression in 293 cells. In contrast to PEI, UPC was non toxic at escalating doses. After intratracheal administration, both polyplexes distributed to the mid-airways, where transgene expression was observed in virtually every epithelial cell, using a sensitive pLacZ reporter containing a translational enhancer element. However, the kinetics of gene expression differed - PEI polyplexes induced a more rapid onset of gene expression than UPC. This was attributed to a more rapid endosomal escape of the PEI polyplexes. Although this resulted in a more efficient gene expression with PEI polyplexes, UPC had an efficiency comparable to that of commonly used cationic lipids. In conclusion, this study provides insights into the use of chitosan as a gene delivery system. It emphasises that chitosan is a nontoxic alternative to other cationic polymers and it forms a platform for further studies of chitosan-based gene delivery systems.

Place, publisher, year, edition, pages
2001. Vol. 8, no 14, 1108-1121 p.
Keyword [en]
nonviral gene therapy, gene delivery, chitosan, polyethylenimine, plasmid DNA, lung epithilium
National Category
Pharmaceutical Sciences Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-37222ISI: 000170288800008PubMedID: 11526458OAI: oai:DiVA.org:uu-37222DiVA: diva2:65121
Note
Addresses: Artursson P, Uppsala Univ, Div Pharmaceut, Dept Pharm, Box 580, SE-75123 Uppsala, Sweden. Uppsala Univ, Div Pharmaceut, Dept Pharm, SE-75123 Uppsala, Sweden. Uppsala Univ, Dept Chem Phys, SE-75123 Uppsala, Sweden. Norwegian Univ Sci & Technol,Available from: 2006-12-19 Created: 2006-12-19 Last updated: 2017-12-06Bibliographically approved

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