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

PY - 2019/1/1

Y1 - 2019/1/1

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

KW - encapsulation

KW - ATPASE ACTIVITY

KW - VIVO

KW - CONTROLLED-RELEASE

KW - MECHANISMS

KW - polypeptides

KW - MICROVASCULAR BLOOD-FLOW

KW - DELIVERY

KW - INSULIN

KW - NANOPARTICLES

KW - IN-VITRO

KW - nanoparticles

KW - amphiphilic random copolymers

KW - C-peptide

KW - diabetes

UR - http://www.scopus.com/inward/record.url?scp=85060580885&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics11010027

DO - 10.3390/pharmaceutics11010027

M3 - Article

AN - SCOPUS:85060580885

VL - 11

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 1

M1 - 27

ER -