DESIGN, CHARACTERIZATION AND ENHANCED BIOAVAILABILITY OF HYDROXYPROPYLCELLULOSE-BASED NOVEL BIOCONJUGATES FOR INCLUSION OF A FLUOROQUINOLONE ANTIBIOTIC – GEMIFLOXACIN
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Published:2021-12-03
Issue:9-10
Volume:55
Page:1019-1027
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ISSN:0576-9787
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Container-title:Cellulose Chemistry and Technology
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language:
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Short-container-title:Cellulose Chem. Technol.
Author:
HUSSAIN MUHAMMAD AJAZ, ,MALIK IRAM,SHAD IQRA,AMJAD FASIHA,AMIN MUHAMMAD,TAHIR MUHAMMAD NAWAZ,ULLAH NISAR,ASHRAF MUHAMMAD,IRFAN MUHAMMAD IMRAN, , , , , , , ,
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. 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.
Publisher
Institutul de Chimie Macromoleculara Petru Poni
Subject
Materials Chemistry,Organic Chemistry