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Adv Pharm Bull. 2021;11(4): 675-683.
doi: 10.34172/apb.2021.076
  Abstract View: 444
  PDF Download: 33

Research Article

Conjugation of Gentamicin to Polyamidoamine Dendrimers Improved Anti-bacterial Properties against Pseudomonas aeruginosa

Hamed Sheykhloo 1 ORCID logo, Morteza Milani 2, Farhood Najafi 3, Farhad Bani 2,4* ORCID logo, Amir Zarebkohan 2,4* ORCID logo

1 Biotechnology Department, Rabe Rashidi University, Tabriz, Iran.
2 Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran.
4 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
*Corresponding Author: Amir Zarebkohan; Tel: +98 41 3355790, Email: zarebkohana@ tbzmed.ac.ir

Abstract

Purpose: This study aimed to design gentamicin-conjugated poly (amidoamine) (PAMAM) dendrimers to increase the therapeutic efficiency of gentamicin against Pseudomonas aeruginosa.

Methods: Gentamicin-presenting dendrimers were synthesized using MAL-PEG3400-NHS as a redox-sensitive linker to attach gentamicin to the surface of G4 PAMAM dendrimers. The gentamicin molecules were thiolated by using Traut reagent. Then, the functionalized gentamicin molecules were attached to PEGylated PAMAM dendrimers through simple and high selectively maleimide (MAL)-thiol reaction. The structure of gentamicin-conjugated PAMAM dendrimers was characterized and confirmed using nuclear magnetic resonance (NMR), dynamic light scattering (DLS), zeta potential analysis, and transmission electron microscopy (TEM) imaging. The antibacterial properties of the synthesized complex were examined on P. aeruginosa and compared to gentamycin alone.

Results: NMR, DLS, zeta potential analysis, and TEM imaging revealed the successful conjugation of gentamicin to PAMAM dendrimers. Data showed the appropriate physicochemical properties of the synthesized nanoparticles. We found a 3-fold increase in the antibacterial properties of gentamicin conjugated to the surface of PAMAM dendrimers compared to non-conjugated gentamicin. Based on data, the anti-biofilm effects of PAMAM-Gentamicin dendrimers increased at least 13 times more than the gentamicin in normal conditions.

Conclusion: Data confirmed that PAMAM dendrimer harboring gentamicin could be touted as a novel smart drug delivery system in infectious conditions.


Keywords: Gentamicin, PAMAM dendrimers, Pseudomonas aeruginosa, Drug delivery, Anti-bacterial capacity

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Submitted: 16 Jul 2020
Revision: 29 Sep 2020
Accepted: 13 Oct 2020
ePublished: 14 Oct 2020
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