DESIGN, CHARACTERIZATION AND ENHANCED BIOAVAILABILITY OF HYDROXYPROPYLCELLULOSE-BASED NOVEL BIOCONJUGATES FOR INCLUSION OF A FLUOROQUINOLONE ANTIBIOTIC – GEMIFLOXACIN

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. Therefore, HPC-gemifloxacin conjugates, i.e., macromolecular prodrugs, were synthesized using acylation reagents, i.e., tosyl chloride and carbonyldiimidazole using N,N-dimethylacetamide as a solvent. The reactions were carried out at 80 °C under stirring for 24 h in inert environment. This strategy of reaction appeared efficient to obtain a high degree of drug substitution (DS = 0.42-1.34) 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 (71-76%). Macromolecular prodrugs with different DS of gemifloxacin (GEM) designed were found soluble in organic solvents. The pharmacokinetic studies showed that the t1/2 and tmax values of GEM from HPC-GEM conjugate were considerably higher, which indicates improved bioavailability of the drug after conjugate formation.

The benefits of macromolecular hydrogen sulfide prodrugs

The potential of H2S can be realised with design of macromolecular prodrugs.