Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5511873 | International Journal of Biological Macromolecules | 2017 | 35 Pages |
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 Lâ1, 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 ÌC, respectively, indicating extraordinary thermal stability imparted to drugs after MPD formation.
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Authors
Khawar Abbas, Muhammad Amin, Muhammad Ajaz Hussain, Muhammad Sher, Syed Nasir Abbas Bukhari, Ibrahim Jantan, Kevin J. Edgar,