Quaternization enhances the transgene expression efficacy of aminoglycoside-derived polymers

Bhavani Miryala, Yunpeng Feng, Ala Omer, Thrimoorthy Potta, Kaushal Rege

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The objective of the present study was to synthesize and investigate the transgene expression efficacy of quaternized derivatives of aminoglycoside polymers in different cancer cell lines. A series of glycidyltrimethylammonium chloride (GTMAC) derivatives of aminoglycoside polymers (GTMAC-AM polymers), containing varying degrees of quaternization (13-45%), were synthesized. The structures and properties of GTMAC-AM polymers were investigated using FT-IR and 1H NMR spectroscopy. Physicochemical factors that influence transgene expression efficacy including DNA binding, hydrodynamic size, zeta potential and cytotoxicity, were determined. Formation of polymer-plasmid DNA complexes was also visualized using atomic force microscopy. GTMAC-AM polymers demonstrated higher transgene expression efficacies compared to their parent polymers, 25 kDa poly(ethyleneimine), as well as Lipofectamine-3000. Our results indicate that quaternization enhances the transgene expression efficacy and reduces the cytotoxicity of aminoglycoside-derived polymers, making it an attractive strategy for nucleic acid delivery with these new materials.

Original languageEnglish (US)
Pages (from-to)18-29
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume489
Issue number1-2
DOIs
StatePublished - Jul 15 2015

ASJC Scopus subject areas

  • Pharmaceutical Science

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