Self-assembled nanoformulation of methylprednisolone succinatewith carboxylated block copolymer for local glucocorticoid therapy

Marat I. Kamalova, Trinh Ðang, Natalia V. Petrova, Alexander V. Laikov, Duong Luong, Rezeda A. Akhmadishina, Andrei Lukashkin, Timur I. Abdullin

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylatedtrifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almostmonodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potentialof −27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPSwere elucidated by comparing copolymers and glucocorticoids with different structure. The micellarstructure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with bloodserum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxi-city in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportationand hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometrywith multiple reaction monitoring which showed increased level of both MPS and methylprednisolonein neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as anadvanced in situ prepared nanoformulation and encourage its further investigation for a potential localglucocorticoid therapy.
Original languageEnglish
Pages (from-to)78-88
Number of pages11
JournalColloids and Surfaces B: Biointerfaces
Volume164
DOIs
Publication statusPublished - 11 Jan 2018

Fingerprint

Methylprednisolone Hemisuccinate
Methylprednisolone
Glucocorticoids
Block copolymers
UCON 50-HB-5100
Micelles
Liquid chromatography
Dilution
Hydrolysis
Hydrodynamics
Copolymers
Availability

Bibliographical note

© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • Methylprednisolone succinate
  • Ethylene oxide and propylene oxide copolymers
  • Nanoformulation
  • Self-assembly
  • Mixed micelles
  • Cellular availability
  • Mass spectrometry
  • Local glucocorticoid therapy

Cite this

Kamalova, M. I., Ðang, T., Petrova, N. V., Laikov, A. V., Luong, D., Akhmadishina, R. A., ... Abdullin, T. I. (2018). Self-assembled nanoformulation of methylprednisolone succinatewith carboxylated block copolymer for local glucocorticoid therapy. 164, 78-88. https://doi.org/10.1016/j.colsurfb.2018.01.014
Kamalova, Marat I. ; Ðang, Trinh ; Petrova, Natalia V. ; Laikov, Alexander V. ; Luong, Duong ; Akhmadishina, Rezeda A. ; Lukashkin, Andrei ; Abdullin, Timur I. / Self-assembled nanoformulation of methylprednisolone succinatewith carboxylated block copolymer for local glucocorticoid therapy. 2018 ; Vol. 164. pp. 78-88.
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abstract = "A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylatedtrifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almostmonodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potentialof −27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPSwere elucidated by comparing copolymers and glucocorticoids with different structure. The micellarstructure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with bloodserum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxi-city in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportationand hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometrywith multiple reaction monitoring which showed increased level of both MPS and methylprednisolonein neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as anadvanced in situ prepared nanoformulation and encourage its further investigation for a potential localglucocorticoid therapy.",
keywords = "Methylprednisolone succinate, Ethylene oxide and propylene oxide copolymers, Nanoformulation, Self-assembly, Mixed micelles, Cellular availability, Mass spectrometry, Local glucocorticoid therapy",
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Self-assembled nanoformulation of methylprednisolone succinatewith carboxylated block copolymer for local glucocorticoid therapy. / Kamalova, Marat I.; Ðang, Trinh; Petrova, Natalia V.; Laikov, Alexander V.; Luong, Duong; Akhmadishina, Rezeda A.; Lukashkin, Andrei; Abdullin, Timur I.

Vol. 164, 11.01.2018, p. 78-88.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Self-assembled nanoformulation of methylprednisolone succinatewith carboxylated block copolymer for local glucocorticoid therapy

AU - Kamalova, Marat I.

AU - Ðang, Trinh

AU - Petrova, Natalia V.

AU - Laikov, Alexander V.

AU - Luong, Duong

AU - Akhmadishina, Rezeda A.

AU - Lukashkin, Andrei

AU - Abdullin, Timur I.

N1 - © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2018/1/11

Y1 - 2018/1/11

N2 - A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylatedtrifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almostmonodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potentialof −27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPSwere elucidated by comparing copolymers and glucocorticoids with different structure. The micellarstructure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with bloodserum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxi-city in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportationand hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometrywith multiple reaction monitoring which showed increased level of both MPS and methylprednisolonein neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as anadvanced in situ prepared nanoformulation and encourage its further investigation for a potential localglucocorticoid therapy.

AB - A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylatedtrifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almostmonodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potentialof −27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPSwere elucidated by comparing copolymers and glucocorticoids with different structure. The micellarstructure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with bloodserum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxi-city in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportationand hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometrywith multiple reaction monitoring which showed increased level of both MPS and methylprednisolonein neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as anadvanced in situ prepared nanoformulation and encourage its further investigation for a potential localglucocorticoid therapy.

KW - Methylprednisolone succinate

KW - Ethylene oxide and propylene oxide copolymers

KW - Nanoformulation

KW - Self-assembly

KW - Mixed micelles

KW - Cellular availability

KW - Mass spectrometry

KW - Local glucocorticoid therapy

U2 - 10.1016/j.colsurfb.2018.01.014

DO - 10.1016/j.colsurfb.2018.01.014

M3 - Article

VL - 164

SP - 78

EP - 88

ER -