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.
Original language | English |
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Pages (from-to) | 1019-1027 |
Number of pages | 9 |
Journal | Cellulose Chemistry and Technology |
Volume | 55 |
Issue number | 9-10 |
DOIs | |
State | Published - 1 Sep 2021 |
Bibliographical note
Funding Information:The sustained release of HPC-GEM conjugate is supported by the half-life (t1/2) data, which has
Publisher Copyright:
© 2021, Publishing House of the Romanian Academy. All rights reserved.
Keywords
- Esterification
- Fluoroquinolone antibiotics
- Gemifloxacin
- Hydroxypropylcellulose
- Macromolecular prodrugs
- Pharmacokinetics
ASJC Scopus subject areas
- Organic Chemistry
- Materials Chemistry