Abstract
Present study deals with the synthesis of macromolecular prodrugs of aceclofenac (ACL) on to hydrophilic polysaccharide hydroxyethylcellulose (HEC). ACL prodrugs synthesized were thoroughly characterized by spectroscopic techniques and found organo-soluble. The esterified prodrugs showed self-assembly behaviour at solvent interface of DMSO/water and appeared as nanoparticles of 200-550 nm diameter. The HEC-ACL conjugates showed significant inhibition (43%) in the levels of interleukin 6 (IL-6) which indicated its immunomodulatory potential. The conjugates showed 81% inhibition in edema created after carrageenan injection. HEC-aceclofenac conjugates appeared biocompatible in cell viability studies. Bioavailability studies revealed that ACL from the conjugate shows plasma half-life of 7.90 h which is significantly higher than unmodified ACL (3.93 h). Moreover, t(max) of 4.0 h with peak plasma concentration (C-max) of 8.27 mu g mL(-1) for ACL from conjugate indicated its enhanced bioavailability.