TY - JOUR

T1 - Polypeptide self-assembled nanoparticles as delivery systems for polymyxins B and E

AU - Iudin, Dmitrii

AU - Zashikhina, Natalia

AU - Demyanova, Elena

AU - Korzhikov-Vlakh, Viktor

AU - Shcherbakova, Elena

AU - Boroznjak, Roman

AU - Tarasenko, Irina

AU - Zakharova, Natalya

AU - Lavrentieva, Antonina

AU - Skorik, Yury

AU - Korzhikova-Vlakh, Evgenia

N1 - Funding Information: Funding: This study was financially supported by the Russian Science Foundation (project no. 19-73-20157). Funding Information: Acknowledgments: N. Zashikhina thanks the G-RISC foundation for one-month scholarship (#C-2019a-9). The authors are grateful to Y.A. Dubrovskii (Almazov National Medical Research Centre, St. Petersburg, Russia) for HPLC-MS measurements. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/9

Y1 - 2020/9

N2 - 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.

AB - 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.

KW - Drug delivery systems

KW - Minimal inhibitory concentration

KW - Peptide antibiotics

KW - Polymyxin loading and release

KW - Polymyxins

KW - Polypeptide nanoparticles

UR - http://www.scopus.com/inward/record.url?scp=85090836750&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/28640584-8b04-3c25-8549-a1ddd84624e1/

U2 - 10.3390/pharmaceutics12090868

DO - 10.3390/pharmaceutics12090868

M3 - Article

AN - SCOPUS:85090836750

VL - 12

SP - 1

EP - 20

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 9

M1 - 868

ER -