Hindawi Publishing Corporation Journal of Biomedicine and Biotechnology Volume 2010, Article ID 284840, 10 pages doi:10.1155/2010/284840 Research Article Gene Transfer into the Lung by Nanoparticle Dextran-Spermine/Plasmid DNA Complexes Syahril Abdullah, 1, 2 Wai Yeng Wendy-Yeo, 1, 2 Hossein Hosseinkhani, 3, 4 Mohsen Hosseinkhani, 5 Ehab Masrawa, 6 Rajesh Ramasamy, 1, 7 Rozita Rosli, 1, 2 Sabariah A. Rahman, 1, 7 and Abraham J. Domb 6 1 UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia 2 Medical Genetics Laboratory, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia 3 Center for Biomedical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA 4 International Research Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women’s Medical University, 8-1, Kawada-cho, Tokyo 162-8666, Japan 5 Center for Cancer Systems Biology, Caritas St. Elizabeth’s Medical Center, Tufts University School of Medicine, MA 02135, USA 6 Department of Medicinal Chemistry and Natural Products, School of Pharmacy, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel 7 Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia Correspondence should be addressed to Syahril Abdullah, syahril@medic.upm.edu.my Received 9 February 2010; Revised 21 April 2010; Accepted 5 May 2010 Academic Editor: Jeffrey Hughes Copyright © 2010 Syahril Abdullah et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A novel cationic polymer, dextran-spermine (D-SPM), has been found to mediate gene expression in a wide variety of cell lines and in vivo through systemic delivery. Here, we extended the observations by determining the optimal conditions for gene expression of D-SPM/plasmid DNA (D-SPM/pDNA) in cell lines and in the lungs of BALB/c mice via instillation delivery. In vitro studies showed that D-SPM could partially protect pDNA from degradation by nuclease and exhibited optimal gene transfer efficiency at D-SPM to pDNA weight-mixing ratio of 12. In the lungs of mice, the levels of gene expression generated by D-SPM/pDNA are highly dependent on the weight-mixing ratio of D-SPM to pDNA, amount of pDNA in the complex, and the assay time postdelivery. Readministration of the complex at day 1 following the first dosing showed no significant effect on the retention and duration of gene expression. The study also showed that there was a clear trend of increasing size of the complexes as the amount of pDNA was increased, where the sizes of the D-SPM/pDNA complexes were within the nanometer range. 1. Introduction The success of gene therapy has largely depended upon the development of delivery vectors, which are able to efficiently and selectively deliver genes to target cells. Viral vectors are able to mediate gene transfer with high effi- ciency with the possibility of long-term gene expression. However, their broad use is affected by the limited size of the genetic material that can be delivered and the possibility of insertional mutagenesis [1]. In light of these concerns, nonviral gene delivery has emerged as a promising alternative. Among the variety of different materials which have been utilized in the production of nonviral vectors [2–5], polycations are considered to be a potent candidate due to their ease of preparation, purification, stability, and the capacity to modify their physicochemical properties [6, 7]. Over the years, a significant number of cationic polymers in linear or branched configuration have been