Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Natalia Zashikhina
  • Vladimir Sharoyko
  • Mariia Antipchik
  • Irina Tarasenko
  • Yurii Anufrikov
  • Antonina Lavrentieva
  • Tatiana Tennikova
  • Evgenia Korzhikova-Vlakh

Organisationseinheiten

Externe Organisationen

  • Russian Academy of Sciences (RAS)
  • Staatliche Universität Sankt Petersburg
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Details

OriginalspracheEnglisch
Aufsatznummer27
FachzeitschriftPharmaceutics
Jahrgang11
Ausgabenummer1
Frühes Online-Datum11 Jan. 2019
PublikationsstatusVeröffentlicht - 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.

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Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications. / Zashikhina, Natalia; Sharoyko, Vladimir; Antipchik, Mariia et al.
in: Pharmaceutics, Jahrgang 11, Nr. 1, 27, 01.2019.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Zashikhina, N, Sharoyko, V, Antipchik, M, Tarasenko, I, Anufrikov, Y, Lavrentieva, A, Tennikova, T & Korzhikova-Vlakh, E 2019, 'Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications', Pharmaceutics, Jg. 11, Nr. 1, 27. https://doi.org/10.3390/pharmaceutics11010027, https://doi.org/10.15488/4530
Zashikhina, N., Sharoyko, V., Antipchik, M., Tarasenko, I., Anufrikov, Y., Lavrentieva, A., Tennikova, T., & Korzhikova-Vlakh, E. (2019). Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications. Pharmaceutics, 11(1), Artikel 27. https://doi.org/10.3390/pharmaceutics11010027, https://doi.org/10.15488/4530
Zashikhina N, Sharoyko V, Antipchik M, Tarasenko I, Anufrikov Y, Lavrentieva A et al. Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications. Pharmaceutics. 2019 Jan;11(1):27. Epub 2019 Jan 11. doi: 10.3390/pharmaceutics11010027, 10.15488/4530
Zashikhina, Natalia ; Sharoyko, Vladimir ; Antipchik, Mariia et al. / Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications. in: Pharmaceutics. 2019 ; Jahrgang 11, Nr. 1.
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title = "Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications",
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. ",
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note = "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.",
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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

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DO - 10.3390/pharmaceutics11010027

M3 - Article

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VL - 11

JO - Pharmaceutics

JF - Pharmaceutics

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ER -

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