Flurbiprofen conjugates based on hydroxyethylcellulose: Synthesis, characterization, pharmaceutical and pharmacological applications

Khawar Abbas; Muhammad Ajaz Hussain; Syed Nasir Abbas Bukhari; Muhammad Amin; Muhammad Nawaz Tahir; Sheshanath V. Bhosale

doi:10.1016/j.arabjc.2018.03.011

Flurbiprofen conjugates based on hydroxyethylcellulose: Synthesis, characterization, pharmaceutical and pharmacological applications

Khawar Abbas
, Muhammad Ajaz Hussain^*
, Syed Nasir Abbas Bukhari
, Muhammad Amin
, Muhammad Nawaz Tahir
, Sheshanath V. Bhosale

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Present study deals with fabrication of macromolecular prodrugs (MPDs) of flurbiprofen (FLB) with hydroxyethylcellulose (HEC). FLB was activated using p-toluenesulfonyl chloride and reacted with pre-dissolved HEC to yield HEC-FLB conjugates 1–3. Resultant prodrugs showed moderate to high degree of substitution (DS: 0.40–1.74) and assembled into nanoparticles of 220–550 nm at water/DMSO interface. Pharmacokinetic studies of HEC-FLB conjugate revealed a t_max of 4.0 h indicating delayed release of FLB while t_1/2 of 10.63 h indicated sustained release characteristics of the conjugate in rabbit model. Pharmacological studies revealed that HEC-FLB conjugates had immunomodulatory potential as results showed 34 and 36% inhibition of Interleukin-6 and tumor necrosis factor-α, respectively. A 79% inhibition of paw edema indicated anti-inflammatory properties of the conjugates. Cell viability studies indicated safety of the conjugates to L929 cell lines up to 24 h in the range of 2–10 mM. Moreover, thermal analysis indicated greater stability of MPDs than FLB.

Original language	English
Pages (from-to)	2101-2109
Number of pages	9
Journal	Arabian Journal of Chemistry
Volume	13
Issue number	1
DOIs	https://doi.org/10.1016/j.arabjc.2018.03.011
State	Published - Jan 2020

Bibliographical note

Funding Information:
K. Abbas gratefully acknowledges financial support provided by the Higher Education Commission (HEC) of Pakistan under “HEC Indigenous 5000 fellowships Scheme”. FLB was generously gifted by Candid Pharmaceuticals Sialkot, Pakistan.

Funding Information:
K. Abbas gratefully acknowledges financial support provided by the Higher Education Commission (HEC) of Pakistan under “HEC Indigenous 5000 fellowships Scheme”. FLB was generously gifted by Candid Pharmaceuticals Sialkot, Pakistan.

Publisher Copyright:
© 2018 King Saud University

Keywords

Anti-inflammatory activity
Flurbiprofen
Hydroxyethylcellulose
Immunomodulatory assay
Prodrug

ASJC Scopus subject areas

General Chemistry
General Chemical Engineering

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10.1016/j.arabjc.2018.03.011

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@article{a75539c54b64472eb7a84e17940e8393,

title = "Flurbiprofen conjugates based on hydroxyethylcellulose: Synthesis, characterization, pharmaceutical and pharmacological applications",

abstract = "Present study deals with fabrication of macromolecular prodrugs (MPDs) of flurbiprofen (FLB) with hydroxyethylcellulose (HEC). FLB was activated using p-toluenesulfonyl chloride and reacted with pre-dissolved HEC to yield HEC-FLB conjugates 1–3. Resultant prodrugs showed moderate to high degree of substitution (DS: 0.40–1.74) and assembled into nanoparticles of 220–550 nm at water/DMSO interface. Pharmacokinetic studies of HEC-FLB conjugate revealed a tmax of 4.0 h indicating delayed release of FLB while t1/2 of 10.63 h indicated sustained release characteristics of the conjugate in rabbit model. Pharmacological studies revealed that HEC-FLB conjugates had immunomodulatory potential as results showed 34 and 36\% inhibition of Interleukin-6 and tumor necrosis factor-α, respectively. A 79\% inhibition of paw edema indicated anti-inflammatory properties of the conjugates. Cell viability studies indicated safety of the conjugates to L929 cell lines up to 24 h in the range of 2–10 mM. Moreover, thermal analysis indicated greater stability of MPDs than FLB.",

keywords = "Anti-inflammatory activity, Flurbiprofen, Hydroxyethylcellulose, Immunomodulatory assay, Prodrug",

author = "Khawar Abbas and Hussain, \{Muhammad Ajaz\} and Bukhari, \{Syed Nasir Abbas\} and Muhammad Amin and Tahir, \{Muhammad Nawaz\} and Bhosale, \{Sheshanath V.\}",

note = "Funding Information: K. Abbas gratefully acknowledges financial support provided by the Higher Education Commission (HEC) of Pakistan under “HEC Indigenous 5000 fellowships Scheme”. FLB was generously gifted by Candid Pharmaceuticals Sialkot, Pakistan. Funding Information: K. Abbas gratefully acknowledges financial support provided by the Higher Education Commission (HEC) of Pakistan under “HEC Indigenous 5000 fellowships Scheme”. FLB was generously gifted by Candid Pharmaceuticals Sialkot, Pakistan. Publisher Copyright: {\textcopyright} 2018 King Saud University",

year = "2020",

month = jan,

doi = "10.1016/j.arabjc.2018.03.011",

language = "English",

volume = "13",

pages = "2101--2109",

journal = "Arabian Journal of Chemistry",

issn = "1878-5352",

number = "1",

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TY - JOUR

T1 - Flurbiprofen conjugates based on hydroxyethylcellulose

T2 - Synthesis, characterization, pharmaceutical and pharmacological applications

AU - Abbas, Khawar

AU - Hussain, Muhammad Ajaz

AU - Bukhari, Syed Nasir Abbas

AU - Amin, Muhammad

AU - Tahir, Muhammad Nawaz

AU - Bhosale, Sheshanath V.

N1 - Funding Information: K. Abbas gratefully acknowledges financial support provided by the Higher Education Commission (HEC) of Pakistan under “HEC Indigenous 5000 fellowships Scheme”. FLB was generously gifted by Candid Pharmaceuticals Sialkot, Pakistan. Funding Information: K. Abbas gratefully acknowledges financial support provided by the Higher Education Commission (HEC) of Pakistan under “HEC Indigenous 5000 fellowships Scheme”. FLB was generously gifted by Candid Pharmaceuticals Sialkot, Pakistan. Publisher Copyright: © 2018 King Saud University

PY - 2020/1

Y1 - 2020/1

N2 - Present study deals with fabrication of macromolecular prodrugs (MPDs) of flurbiprofen (FLB) with hydroxyethylcellulose (HEC). FLB was activated using p-toluenesulfonyl chloride and reacted with pre-dissolved HEC to yield HEC-FLB conjugates 1–3. Resultant prodrugs showed moderate to high degree of substitution (DS: 0.40–1.74) and assembled into nanoparticles of 220–550 nm at water/DMSO interface. Pharmacokinetic studies of HEC-FLB conjugate revealed a tmax of 4.0 h indicating delayed release of FLB while t1/2 of 10.63 h indicated sustained release characteristics of the conjugate in rabbit model. Pharmacological studies revealed that HEC-FLB conjugates had immunomodulatory potential as results showed 34 and 36% inhibition of Interleukin-6 and tumor necrosis factor-α, respectively. A 79% inhibition of paw edema indicated anti-inflammatory properties of the conjugates. Cell viability studies indicated safety of the conjugates to L929 cell lines up to 24 h in the range of 2–10 mM. Moreover, thermal analysis indicated greater stability of MPDs than FLB.

AB - Present study deals with fabrication of macromolecular prodrugs (MPDs) of flurbiprofen (FLB) with hydroxyethylcellulose (HEC). FLB was activated using p-toluenesulfonyl chloride and reacted with pre-dissolved HEC to yield HEC-FLB conjugates 1–3. Resultant prodrugs showed moderate to high degree of substitution (DS: 0.40–1.74) and assembled into nanoparticles of 220–550 nm at water/DMSO interface. Pharmacokinetic studies of HEC-FLB conjugate revealed a tmax of 4.0 h indicating delayed release of FLB while t1/2 of 10.63 h indicated sustained release characteristics of the conjugate in rabbit model. Pharmacological studies revealed that HEC-FLB conjugates had immunomodulatory potential as results showed 34 and 36% inhibition of Interleukin-6 and tumor necrosis factor-α, respectively. A 79% inhibition of paw edema indicated anti-inflammatory properties of the conjugates. Cell viability studies indicated safety of the conjugates to L929 cell lines up to 24 h in the range of 2–10 mM. Moreover, thermal analysis indicated greater stability of MPDs than FLB.

KW - Anti-inflammatory activity

KW - Flurbiprofen

KW - Hydroxyethylcellulose

KW - Immunomodulatory assay

KW - Prodrug

UR - https://www.scopus.com/pages/publications/85044568073

U2 - 10.1016/j.arabjc.2018.03.011

DO - 10.1016/j.arabjc.2018.03.011

M3 - Article

AN - SCOPUS:85044568073

SN - 1878-5352

VL - 13

SP - 2101

EP - 2109

JO - Arabian Journal of Chemistry

JF - Arabian Journal of Chemistry

IS - 1

ER -

Flurbiprofen conjugates based on hydroxyethylcellulose: Synthesis, characterization, pharmaceutical and pharmacological applications

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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