title: Preparation and in vitro/in vivo evaluation of cyclosporin A-loaded nanodecorated ocular implants for subconjunctival application.
abstract: In terms of ocular drug delivery, biodegradable implant systems have several advantages including the ability to provide constant drug concentration at the target site, no necessity for surgical removal, and minimum systemic side effects. Cyclosporin A (CsA) is a neutral, hydrophobic, cyclic peptide of amino acids that frequently used for dry eye disease treatment. The aim of this study was to develop a nanoparticle-loaded implant system for sustained-release CsA delivery following subconjunctival implantation. Poly(lactide-co-glycolide) (85:15) or poly-ε-caprolactone (PCL) were used to prepare two different nanoparticle formulations. These nanoparticles loaded into PCL or poly(lactide-co-caprolactone) implant formulations were prepared by two different methods, which were molding and electrospinning. Size and zeta potential of nanoparticles were determined and the morphology of the formulations were investigated by scanning electron microscopy. CsA-loading efficiencies were calculated and the in vitro degradation and in vitro release studies were performed. MTT test was also performed using L929 fibroblast cells to evaluate the cytotoxicity of the formulations. PCL-PCL-NP-I formulation was implanted to Swiss Albino mice with induced dry eye syndrome to evaluate the efficacy. In vitro release studies showed that the release from the formulations continues between 30 and 60 days, and the cell viability was found to be 77.4%-99.0%. In vivo studies showed that healing is significantly faster in the presence of the selected implant formulation. Results indicated that nanodecorated implants are promising ocular carriers for controlled-release CsA application.
authors.affiliation: Hacettepe University Faculty of Pharmacy, Pharmaceutical Technology Department, Ankara, Turkey.
authors.forename: Sibel Bozdağ
authors.initials: SB
authors.lastname: Pehlivan
authors.forename: Burçin
authors.initials: B
authors.lastname: Yavuz
authors.forename: Semih
authors.initials: S
authors.lastname: Çalamak
authors.forename: Kezban
authors.initials: K
authors.lastname: Ulubayram
authors.forename: Abbas
authors.initials: A
authors.lastname: Kaffashi
authors.forename: İmran
authors.initials: İ
authors.lastname: Vural
authors.forename: Hasan Basri
authors.initials: HB
authors.lastname: Çakmak
authors.forename: Meltem Ezgi
authors.initials: ME
authors.lastname: Durgun
authors.forename: Emir Baki
authors.initials: EB
authors.lastname: Denkbaş
authors.forename: Nurşen
authors.initials: N
authors.lastname: Ünlü
mesh_terms: D000818:Animals; D003228:Conjunctiva / Q000187:drug effects*; D016572:Cyclosporine / Q000008:administration & dosage / Q000138:chemical synthesis*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis; D004341:Drug Evaluation / Q000379:methods; D004343:Drug Implants / Q000008:administration & dosage / Q000138:chemical synthesis*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011091:Polyesters / Q000008:administration & dosage / Q000138:chemical synthesis
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D011091:Polyesters; C033616:poly(lactide); D016572:Cyclosporine
keywords: controlled release; cyclosporin A; drug delivery; formulation; nano fiber; nanoparticle; ocular implants; ophtalmic drug delivery; subconjunctival application