title: Extended release and enhanced bioavailability of moxifloxacin conjugated with hydrophilic cellulose ethers.
abstract: Macromolecular prodrugs (MPDs) of moxifloxacin were fabricated based on hydroxypropylcellulose (HPC) and hydroxyethylcellulose (HEC). UV/Vis spectrophotometry was employed to determine covalently loaded drug content (DC) of each conjugate. The degree of substitution (DS) of moxifloxacin attained ranged from 0.27 to 0.38 (HPC) and 0.19 to 0.26 (HEC) per anhydroglucose unit (AGU), respectively. Transmission electron microscopic analyses showed that HPC-moxifloxacin conjugates self-assembled into nanowires of ∼ 30 nm diameters while HEC-moxifloxacin conjugates self-assembled into nanoparticles of 150-350 nm. In vitro drug release studies revealed that 15 and 49% moxifloxacin release occurred from the HPC-moxifloxacin conjugate after 6h at pH 1.2 and 7.4, respectively. Similarly, moxifloxacin release from HEC-moxifloxacin conjugates was 15 and 39% at pH 1.2 and 7.4, respectively. Bioavailability and pharmacokinetic studies in rabbits showed that both HPC- and HEC-conjugates exhibited significantly enhanced moxifloxacin plasma half-life, over 24h, confirming sustained release and enhanced bioavailability (AUC 2.0-2.1 times higher) of moxifloxacin.
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan.
authors.forename: Nazia S
authors.initials: NS
authors.lastname: Abbas
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Amin
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan. Electronic address: majaz172@yahoo.com.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Hussain
authors.affiliation: Department of Sustainable Biomaterials, and Macromolecules and Interfaces Institute, Virginia Tech, 230 Cheatham Hall, Blacksburg, VA 24061, United States.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Edgar
authors.affiliation: Institute of Inorganic and Analytical Chemistry, Johannes Guttenberg University, Duesbergweg 10-14, Mainz 55128, Germany.
authors.forename: Muhammad N
authors.initials: MN
authors.lastname: Tahir
authors.affiliation: Institute of Inorganic and Analytical Chemistry, Johannes Guttenberg University, Duesbergweg 10-14, Mainz 55128, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Tremel
mesh_terms: D000818:Animals; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008297:Male; D000077266:Moxifloxacin; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits
chemical_list: D003692:Delayed-Action Preparations; D024841:Fluoroquinolones; D011355:Prodrugs; D002482:Cellulose; C002283:hydroxyethylcellulose; C008079:hydroxypropylcellulose; D000077266:Moxifloxacin
keywords: Hydroxyethylcellulose; Hydroxypropylcellulose; Moxifloxacin; Nano-assembly; Pharmacokinetics; Prodrugs