Dextran-spermine-based polyplexes - Evaluation of transgene expression and of local and systemic toxicity in mice

Hagit Eliyahu, Aviva Joseph, Tony Azzam, Yechezkel Barenholz, Abraham J. Domb

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Gene delivery using self-assembled polyplexes, formed between negatively charged nucleic acids and cationic polymers, have several drawbacks including low transgene expression and toxicity effects related to their positive charge. Recently, a novel cationic polymer based on dextran-spermine (D-SPM) was developed for gene delivery. This polymer showed systemic biodistribution upon local administration (intramuscular (i.m.) and intranasal (i.n.)) followed by transgene expression in organs remote from the site of injection (liver and lungs). Polyplexes based on D-SPM were administered both i.m. and i.n. to BALB/c female mice. LacZ expression in the liver, lungs, and muscles was assessed using whole-mount 5-bromo-4-chloro-3-indolyl β-d-galactopyranoside (X-gal) staining and paraffin sectioning. The local toxicity in these organs was evaluated from hematoxylin and eosin stained sections. The systemic toxicity of the polymer and polyplexes was estimated by comparing the mice total weight, major organ weights, blood counts (primarily white blood cells (WBC) and platelets), and serum transaminases, to those of control animals (which received PBS). Transgene expression using D-SPM polyplexes was dependent upon the dosage and the polyplexes (+/-) charge ratio. Using the i.m. and i.n. routes of administration the transfection occurred primarily in the bronchial epithelial cells, pneumocytes, and bronchial alveoli of the lungs; in the muscle's fibrocytes; and in the liver's hepatocytes. Histopathological assays revealed mild toxicity in muscle and no abnormal findings in liver and lung. No systemic toxicity was obtained, as we did not find decrease in WBC count or platelet and no increase in serum transaminases. In addition, mice body weights and major organ weights were similar to the control group at both 2 and 28 days post-administration. This study demonstrates systemic transfection efficacy upon local administration of D-SPM complexes with good tolerability and low toxicity.

Original languageEnglish
Pages (from-to)1636-1645
Number of pages10
Issue number8
StatePublished - Mar 2006
Externally publishedYes

Bibliographical note

Funding Information:
This is supported by the following observations:


This is supported by the following observations:

FundersFunder number
French–Israel Cooperation on Gene Therapy
US–Israel Binational Fund
United States-Israel Binational Science Foundation
Israel Science Foundation


    • Gene delivery
    • Polycation
    • Toxicity
    • Transgene expression


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