Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E
1
Institute of Macromolecular Compounds, Russian Academy of Sciences, 199004 St. Petersburg, Russia
2
Saint-Petersburg State University, Institute of Chemistry, 198584 St. Petersburg, Russia
3
State Research Institute of Highly Pure Biopreparations, Federal Medical-Biological Agency, 197110 St. Petersburg, Russia
4
Department of Materials and Environmental Technology, Tallinn University of Technology, 19086 Tallinn, Estonia
5
Institute of Technical Chemistry, Gottfried-Wilhelm-Leibniz University of Hannover, 30167 Hannover, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(9), 868; https://doi.org/10.3390/pharmaceutics12090868
Received: 13 August 2020 / Revised: 2 September 2020 / Accepted: 9 September 2020 / Published: 11 September 2020
(This article belongs to the Special Issue Advances in Delivering Protein and Peptide Therapeutics)
Polymyxins are peptide antibiotics that are highly efficient against many multidrug resistant pathogens. However, the poor stability of polymyxins in the bloodstream requires the administration of high drug doses that, in turn, can lead to polymyxin toxicity. Consequently, different delivery systems have been considered for polymyxins to overcome these obstacles. In this work, we report the development of polymyxin delivery systems based on nanoparticles obtained from the self-assembly of amphiphilic random poly(l-glutamic acid-co-d-phenylalanine). These P(Glu-co-dPhe) nanoparticles were characterized in terms of their size, surface charge, stability, cytotoxicity, and uptake by macrophages. The encapsulation efficiency and drug loading into P(Glu-co-dPhe) nanoparticles were determined for both polymyxin B and E. The release kinetics of polymyxins B and E from nanoformulations was studied and compared in buffer solution and human blood plasma. The release mechanisms were analyzed using a number of mathematical models. The minimal inhibitory concentrations of the nanoformulations were established and compared with those determined for the free antibiotics.
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Keywords:
peptide antibiotics; polymyxins; drug delivery systems; polypeptide nanoparticles; polymyxin loading and release; minimal inhibitory concentration
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style
Iudin, D.; Zashikhina, N.; Demyanova, E.; Korzhikov-Vlakh, V.; Shcherbakova, E.; Boroznjak, R.; Tarasenko, I.; Zakharova, N.; Lavrentieva, A.; Skorik, Y.; Korzhikova-Vlakh, E. Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E. Pharmaceutics 2020, 12, 868.
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