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

doi:10.1016/j.colsurfb.2018.01.014

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 journal › Article › peer-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 language	English
Pages (from-to)	78-88
Number of pages	11
Journal	Colloids and Surfaces B: Biointerfaces
Volume	164
DOIs	https://doi.org/10.1016/j.colsurfb.2018.01.014
Publication status	Published - 11 Jan 2018

Bibliographical note

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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1-s2.0-S0927776518300146-main.pdfAccepted author manuscript, 562 KBLicence: CC BY-NC-ND

Andrei Lukashkin
- A.Lukashkinbrighton.acuk
Person: Academic

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title = "Self-assembled nanoformulation of methylprednisolone succinatewith carboxylated block copolymer for local glucocorticoid therapy",

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",

author = "Kamalova, {Marat I.} and Trinh {\DH}ang and Petrova, {Natalia V.} and Laikov, {Alexander V.} and Duong Luong and Akhmadishina, {Rezeda A.} and Andrei Lukashkin and Abdullin, {Timur I.}",

note = "{\textcopyright} 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/",

year = "2018",

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doi = "10.1016/j.colsurfb.2018.01.014",

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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.

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

SN - 0927-7765

VL - 164

SP - 78

EP - 88

JO - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

ER -

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

Abstract

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Keywords

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