title: Novel dexamethasone-loaded nanomicelles for the intermediate and posterior segment uveitis.
abstract: Development and characterization of dexamethasone (DEX)-encapsulated polymeric nanomicelles have been reported. A low molecular weight di-block copolymer was synthesized and characterized for its structure, molecular weights, critical micelle concentration (CMC), and cytotoxicity in ocular cells. In order to delineate the effects of drug-polymer interactions on drug solubilization in micelle core, a response surface methodology was generated with the help of SAS 9.02 (exploratory model). The method for preparing micelle was modified based on the results obtained from exploratory model. The formulation was optimized by response surface methodology (optimization model) to achieve DEX solubility of above 1 mg/mL. The optimized formulation was characterized for DEX solubility, nanomicelle size, polydispersity index, surface morphology, in vitro transport across conjunctival cell line, and ex vivo transport across excised rabbit sclera. Nanomicelles exhibited average sizes in range of 25-30 nm with unimodel size distribution and low polydispersity of 0.125. Nanomicelles increased DEX permeability by 2 times across conjunctival cell line and by 2.5 times across the excised rabbit sclera as compared to DEX suspension. A design of experiment (DOE) strategy was successfully applied to understand the effects of drug-polymer interaction on drug solubility. DOE was also employed to achieve optimal formulation with high DEX solubility. Nanomicellar formulation significantly enhanced DEX permeability across the excised rabbit sclera. Therefore, nanomicellar formulation may provide therapeutic levels in the back of the eye following topical administration.
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, Missouri, 64108-2718, USA.
authors.forename: Ravi D
authors.initials: RD
authors.lastname: Vaishya
authors.forename: Mitan
authors.initials: M
authors.lastname: Gokulgandhi
authors.forename: Sulabh
authors.initials: S
authors.lastname: Patel
authors.forename: Mukul
authors.initials: M
authors.lastname: Minocha
authors.forename: Ashim K
authors.initials: AK
authors.lastname: Mitra
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003228:Conjunctiva / Q000166:cytology / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008823:Micelles; D053758:Nanoparticles; D011817:Rabbits; D012590:Sclera / Q000378:metabolism; D012995:Solubility; D015867:Uveitis, Intermediate / Q000188:drug therapy*; D015866:Uveitis, Posterior / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D008823:Micelles; D003907:Dexamethasone