title: Comparative studies for ciprofloxacin hydrochloride pre-formed gels and thermally triggered (in situ) gels: in vitro and in vivo appraisal using a bacterial keratitis model in rabbits.
abstract: This article reports on comparative in vitro characterization and in vivo evaluation of pre-formed cellulose-based gels, methylcellulose (MC) and carboxymethylcellulose sodium (CMC) and in situ gel-forming Pluronic F127 (PL) for ocular delivery of ciprofloxacin hydrochloride (Cipro) by using a bacterial keratitis model and histological corneal examination. Drug-polymer interactions were studied employing thermal analysis. Further, different concentrations (1-3% w/w or 10-30% w/w) of gels depending on the nature of the polymer used were prepared, characterized for clarity, pH, rheology and in vitro release. Selected gel formulations were evaluated for ocular delivery to Staphylococcus aureus-infected rabbit corneas; and ocular toxicity through histological examination of the cornea. The results demonstrated no Cipro-polymers physicochemical interactions and pseudoplastic flow for all gels used at 35 °C. Both polymer concentrations and drug solubility in the gels are dominantly the rate-determining factors for in vitro drug release. The corneal healing rate for all gel-based formulations was significantly faster (p < 0.05) than that for Cipro solution-treated rabbits. PL-based gel induced significant swelling/edema of the corneal stroma, compared with MC- and CMC-based gels. In conclusion, cellulose-based polymers have superior ocular tolerability/dramatically less irritant; and superior efficacy with more convenient administration compared with PL and Cipro solution, respectively.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Minia University , Minia , Egypt.
authors.forename: Hamdy
authors.initials: H
authors.lastname: Abdelkader
authors.forename: Heba F
authors.initials: HF
authors.lastname: Mansour
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003315:Cornea / Q000187:drug effects / Q000382:microbiology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005260:Female; D005782:Gels / Q000737:chemistry; D007634:Keratitis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D008747:Methylcellulose / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits; D012212:Rheology; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D014783:Viscosity
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D005782:Gels; D020442:Poloxamer; D002939:Ciprofloxacin; D008747:Methylcellulose; D002266:Carboxymethylcellulose Sodium
keywords: In situ gel; keratitis; methylcellulose; ocular delivery; pre-formed gel; viscosity