Designing novel bioconjugates of hydroxyethyl cellulose and salicylates for potential pharmaceutical and pharmacological applications

Khawar Abbas, Muhammad Amin, Muhammad Ajaz Hussain, Muhammad Sher, Bukhari Syed Nasir Abbas, Ibrahim Jantan, Kevin J. Edgar

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

This deals with fabrication of macromolecular prodrugs (MPDs) of salicylic acid (SA) and aspirin (ASP) based on a hydrophilic cellulose ether, hydroxyethyl cellulose (HEC). Degrees of substitution (DS) of SA and ASP per HEC repeating unit (HEC-RU) were achieved ranging from 0.60 to 2.18 and 0.53 to1.50, respectively. The amphiphilic HEC-SA conjugate 2 assembled into nanowire-like structures, while HEC-ASP conjugate 6 formed nanoparticles (diameter 300–00 nm) at a water/DMSO interface. After oral administration in rabbit models, conjugates 2 and 6 showed plasma half-life of 6.96 and 7.01 h with maximum plasma concentration (Cmax) of 15.27 and 23.01 μg L−1, respectively, and each reached peak plasma concentration (tmax) at 4.0 h. Immunomodulatory assays (interleukin 6 and tumor necrosis factor-α values) revealed that anti-inflammatory properties of SA and ASP were unaltered in conjugates. Swelling inhibition of 61 and 71% was observed for conjugates 2 and 6, respectively, in a carrageenan induced paw edema test. Cytotoxic profiling (MTT assay) showed that conjugates were safe for administration in the concentration range of 2–10 mM up to 24 h. Thermal analyses revealed that Tdm values of SA and ASP conjugates were increased by 99 and 154 ̊C, respectively, indicating extraordinary thermal stability imparted to drugs after MPD formation.

Original languageEnglish
Pages (from-to)441-450
Number of pages10
JournalInternational Journal of Biological Macromolecules
Volume103
DOIs
Publication statusPublished - 1 Oct 2017

Fingerprint

Salicylic Acid
Salicylates
Cellulose
Aspirin
Pharmacology
Pharmaceutical Preparations
Prodrugs
Plasmas
Assays
Hot Temperature
Nanowires
Carrageenan
Dimethyl Sulfoxide
Ether
Nanoparticles
Oral Administration
Half-Life
Swelling
Interleukin-6
Edema

Keywords

  • Cytotoxicity
  • Hydroxyethyl cellulose
  • Immunomodulatory assay
  • Pharmacokinetics
  • Salicylates

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Designing novel bioconjugates of hydroxyethyl cellulose and salicylates for potential pharmaceutical and pharmacological applications. / Abbas, Khawar; Amin, Muhammad; Hussain, Muhammad Ajaz; Sher, Muhammad; Syed Nasir Abbas, Bukhari; Jantan, Ibrahim; Edgar, Kevin J.

In: International Journal of Biological Macromolecules, Vol. 103, 01.10.2017, p. 441-450.

Research output: Contribution to journalArticle

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