Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | 868 |
| Seiten (von - bis) | 1-20 |
| Seitenumfang | 20 |
| Fachzeitschrift | Pharmaceutics |
| Jahrgang | 12 |
| Ausgabenummer | 9 |
| Publikationsstatus | Veröffentlicht - 11 Sept. 2020 |
Abstract
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.
ASJC Scopus Sachgebiete
- Pharmakologie, Toxikologie und Pharmazie (insg.)
- Pharmazeutische Wissenschaften
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in: Pharmaceutics, Jahrgang 12, Nr. 9, 868, 11.09.2020, S. 1-20.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
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.
PY - 2020/9/11
Y1 - 2020/9/11
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
U2 - 10.3390/pharmaceutics12090868
DO - 10.3390/pharmaceutics12090868
M3 - Article
C2 - 32933030
AN - SCOPUS:85090836750
VL - 12
SP - 1
EP - 20
JO - Pharmaceutics
JF - Pharmaceutics
IS - 9
M1 - 868
ER -