Details
| Original language | English |
|---|---|
| Article number | 27 |
| Journal | Pharmaceutics |
| Volume | 11 |
| Issue number | 1 |
| Early online date | 11 Jan 2019 |
| Publication status | Published - Jan 2019 |
Abstract
The development and application of novel nanospheres based on cationic and anionic random amphiphilic polypeptides with prolonged stability were proposed. The random copolymers, e.g., poly(L-lysine-co-D-phenylalanine) (P(Lys-co-DPhe)) and poly(L-glutamic acid-co-D-phenylalanine) (P(Glu-co-DPhe)), with different amount of hydrophilic and hydrophobic monomers were synthesized. The polypeptides obtained were able to self-assemble into nanospheres. Such characteristics as size, PDI and ζ-potential of the nanospheres were determined, as well as their dependence on pH was also studied. Additionally, the investigation of their biodegradability and cytotoxicity was performed. The prolonged stability of nanospheres was achieved via introduction of D-amino acids into the polypeptide structure. The cytotoxicity of nanospheres obtained was tested using HEK-293 cells. It was proved that no cytotoxicity up to the concentration of 500 µg/mL was observed. C-peptide delivery systems were realized in two ways: (1) peptide immobilization on the surface of P(Glu-co-DPhe) nanospheres; and (2) peptide encapsulation into P(Lys-co-DPhe) systems. The immobilization capacity and the dependence of C-peptide encapsulation efficiency, as well as maximal loading capacity, on initial drug concentration was studied. The kinetic of drug release was studied at model physiological conditions. Novel formulations of a long-acting C-peptide exhibited their effect ex vivo by increasing activity of erythrocyte Na + /K + -adenosine triphosphatase.
Keywords
- Amphiphilic random copolymers, Diabetes, Encapsulation, Polypeptides
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
Sustainable Development Goals
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In: Pharmaceutics, Vol. 11, No. 1, 27, 01.2019.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications
AU - Zashikhina, Natalia
AU - Sharoyko, Vladimir
AU - Antipchik, Mariia
AU - Tarasenko, Irina
AU - Anufrikov, Yurii
AU - Lavrentieva, Antonina
AU - Tennikova, Tatiana
AU - Korzhikova-Vlakh, Evgenia
N1 - Funding Information: This research was executed as a part of a government assignment (0096-2016-0004). Acknowledgments: N.Z. acknowledges the G-RISC program for personal student scholarship for one-month traineeship in Germany. Thermogravimetric and Calorimetric Research Centre Saint-Petersburg State University acknowledged for Microcalorimetric experiments.
PY - 2019/1
Y1 - 2019/1
N2 - The development and application of novel nanospheres based on cationic and anionic random amphiphilic polypeptides with prolonged stability were proposed. The random copolymers, e.g., poly(L-lysine-co-D-phenylalanine) (P(Lys-co-DPhe)) and poly(L-glutamic acid-co-D-phenylalanine) (P(Glu-co-DPhe)), with different amount of hydrophilic and hydrophobic monomers were synthesized. The polypeptides obtained were able to self-assemble into nanospheres. Such characteristics as size, PDI and ζ-potential of the nanospheres were determined, as well as their dependence on pH was also studied. Additionally, the investigation of their biodegradability and cytotoxicity was performed. The prolonged stability of nanospheres was achieved via introduction of D-amino acids into the polypeptide structure. The cytotoxicity of nanospheres obtained was tested using HEK-293 cells. It was proved that no cytotoxicity up to the concentration of 500 µg/mL was observed. C-peptide delivery systems were realized in two ways: (1) peptide immobilization on the surface of P(Glu-co-DPhe) nanospheres; and (2) peptide encapsulation into P(Lys-co-DPhe) systems. The immobilization capacity and the dependence of C-peptide encapsulation efficiency, as well as maximal loading capacity, on initial drug concentration was studied. The kinetic of drug release was studied at model physiological conditions. Novel formulations of a long-acting C-peptide exhibited their effect ex vivo by increasing activity of erythrocyte Na + /K + -adenosine triphosphatase.
AB - The development and application of novel nanospheres based on cationic and anionic random amphiphilic polypeptides with prolonged stability were proposed. The random copolymers, e.g., poly(L-lysine-co-D-phenylalanine) (P(Lys-co-DPhe)) and poly(L-glutamic acid-co-D-phenylalanine) (P(Glu-co-DPhe)), with different amount of hydrophilic and hydrophobic monomers were synthesized. The polypeptides obtained were able to self-assemble into nanospheres. Such characteristics as size, PDI and ζ-potential of the nanospheres were determined, as well as their dependence on pH was also studied. Additionally, the investigation of their biodegradability and cytotoxicity was performed. The prolonged stability of nanospheres was achieved via introduction of D-amino acids into the polypeptide structure. The cytotoxicity of nanospheres obtained was tested using HEK-293 cells. It was proved that no cytotoxicity up to the concentration of 500 µg/mL was observed. C-peptide delivery systems were realized in two ways: (1) peptide immobilization on the surface of P(Glu-co-DPhe) nanospheres; and (2) peptide encapsulation into P(Lys-co-DPhe) systems. The immobilization capacity and the dependence of C-peptide encapsulation efficiency, as well as maximal loading capacity, on initial drug concentration was studied. The kinetic of drug release was studied at model physiological conditions. Novel formulations of a long-acting C-peptide exhibited their effect ex vivo by increasing activity of erythrocyte Na + /K + -adenosine triphosphatase.
KW - Amphiphilic random copolymers
KW - Diabetes
KW - Encapsulation
KW - Polypeptides
UR - http://www.scopus.com/inward/record.url?scp=85060580885&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics11010027
DO - 10.3390/pharmaceutics11010027
M3 - Article
C2 - 30641932
AN - SCOPUS:85060580885
VL - 11
JO - Pharmaceutics
JF - Pharmaceutics
IS - 1
M1 - 27
ER -