Nanostructure formation in aqueous solution of amphiphilic copolymers of 2-( N, N-dimethylaminoethyl)methacrylate and alkylacrylate: Characterization, antimicrobial activity, DNA binding, and cytotoxicity studies

Three amphiphilic random copolymers poly(2-(dimethylaminoethyl)methacrylate-co-alkylacrylate) (where, alkyl = hexyl, octyl, dodecyl) with 16 mol% hydrophobic substitution were synthesized. Surface tension, viscosity, fluorescence probe, dynamic light scattering (DLS), as well as transmission electro...

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Veröffentlicht in:International journal of pharmaceutics 2011-07, Vol.414 (1), p.298-311
Hauptverfasser: Dutta, Pranabesh, Dey, Joykrishna, Shome, Anshupriya, Das, Prasanta Kumar
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Sprache:eng
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Zusammenfassung:Three amphiphilic random copolymers poly(2-(dimethylaminoethyl)methacrylate-co-alkylacrylate) (where, alkyl = hexyl, octyl, dodecyl) with 16 mol% hydrophobic substitution were synthesized. Surface tension, viscosity, fluorescence probe, dynamic light scattering (DLS), as well as transmission electron microscopic (TEM) techniques were utilized to investigate self-assembly formation by the hydrophobically modified polymers (HMPs) in pH 5. Formation of hydrophobic domains through inter-polymer chain interaction of the copolymer in dilute solution was confirmed by fluorescence probe studies. Average hydrodynamic diameter of the copolymer aggregates at different polymer concentration was measured by DLS studies. The copolymer with shorter hydrophobic chain exhibits larger hydrodynamic diameter in dilute solution, which decreased with either increase of concentration or increase of hydrophobic chain length. TEM images of the dilute solutions of the copolymers with shorter as well as with longer hydrophobic chain exhibit spherical aggregates of different sizes. The antimicrobial activity of the copolymers was evaluated by measuring the minimum inhibitory concentration value against one Gram-positive bacterium Bacillus subtilis and one Gram-negative bacterium Escherichia coli. The copolymer with the octyl group as pendent hydrophobic chain was found to be more effective in killing these microorganisms. The interaction of the cationic copolymers with calf-thymus DNA was studied by fluorescence quenching method. The polymer-DNA binding was found to be purely electrostatic in nature. The hydrophobes on the polymer backbone were found to have a significant influence on the binding process. Biocompatibility studies of the copolymers in terms of cytotoxicity measurements were finally performed at different concentrations of the HMPs to evaluate their potential application in biomedical fields.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2011.05.006