Quaternization enhances the transgene expression efficacy of aminoglycoside-derived polymers

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 <sup>1</sup>H 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

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Aminoglycosides
Transgenes
Polymers
Atomic Force Microscopy
DNA
Hydrodynamics
Nucleic Acids
Plasmids
Magnetic Resonance Spectroscopy
Cell Line
glycidyl trimethylammonium
Neoplasms

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Quaternization enhances the transgene expression efficacy of aminoglycoside-derived polymers. / Miryala, Bhavani; Feng, Yunpeng; Omer, Ala; Potta, Thrimoorthy; Rege, Kaushal.

In: International Journal of Pharmaceutics, Vol. 489, No. 1-2, 15.07.2015, p. 18-29.

Research output: Contribution to journalArticle

Miryala, Bhavani ; Feng, Yunpeng ; Omer, Ala ; Potta, Thrimoorthy ; Rege, Kaushal. / Quaternization enhances the transgene expression efficacy of aminoglycoside-derived polymers. In: International Journal of Pharmaceutics. 2015 ; Vol. 489, No. 1-2. pp. 18-29.
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