Design, characterization and enhanced bioavailability of hydroxypropylcellulose-naproxen conjugates

Abstract Polysaccharides are beneficially used as drug carriers via prodrug formation and offer a mechanism for better effectiveness and delivery of the drug. The unique geometry of hydroxypropylcellulose (HPC), a polysaccharide, allows the attachment of drug molecules with a higher degree of substitution because the hydroxyls groups are projected outside the HPC chains. Therefore HPC-Naproxen conjugates, i.e., macromolecular prodrugs, were synthesized using a powerful acylation reagent carbonyldiimadazole (CDI) in N,N' dimethylacetamide (DMAc) solvent. The reactions were carried out at 80°C under stirring for 24 h and inert environment. This reaction strategy appeared efficient to obtain a high degree of drug substitution (DS= 0.88-1.40) on the polymer parent chain as calculated by UV-visible spectrophotometry after hydrolysis of the samples. The method provides high efficacy as product yields were high (77-81%). Macromolecular prodrugs (MPDs) with different DS of naproxen designed were found soluble in organic solvents.