title: In vivo tissue distribution and efficacy studies for cyclosporin A loaded nano-decorated subconjunctival implants.
abstract: Biodegradable implants are promising drug delivery systems for sustained release ocular drug delivery with the benefits such as minimum systemic side effects, constant drug concentration at the target site and getting cleared without surgical removal. Dry eye syndrome (DES) is a common disease characterized with the changes in ocular epithelia surface and results in inflammatory reaction that might lead to blindness. Cyclosporin A (CsA) is a cyclic peptide that is frequently employed for the treatment of DES and it needs to be applied several times a day in tear drops form. The aim of this study was to evaluate in vivo behavior and efficacy of the developed nano-decorated subconjunctival implant systems for sustained release CsA delivery. Biodegradable Poly-ɛ-caprolactone (PCL) implant or micro-fiber implants containing CsA loaded poly-lactide-co-glycolide (85:15) (PLGA) or PCL nanoparticles were prepared in order to achieve sustained release. Two of the formulations PCL-PLGA-NP-F and PCL-PCL-NP-I were selected for in vivo evaluation based on their in vitro characteristics determined in our previous study. In this study, formulations were implanted to Swiss Albino mice with induced dry eye syndrome to investigate the ocular distribution of CsA following subconjunctival implantation and to evaluate the efficacy. Tissue distribution study indicated that CsA was present in ocular tissues such as cornea, sclera and lens even 90 days after the application and blood CsA levels were found lower than ocular tissues. Efficacy studies also showed that application of CsA-loaded fiber implant formulation resulted in faster recovery based on their staining scores.
authors.affiliation: a Pharmaceutical Technology Department, Faculty of Pharmacy.
authors.forename: Burçin
authors.initials: B
authors.lastname: Yavuz
authors.affiliation: a Pharmaceutical Technology Department, Faculty of Pharmacy.
authors.forename: Sibel
authors.initials: S
authors.lastname: Bozdağ Pehlivan
authors.affiliation: b Nanotechnology and Nanomedicine Department.
authors.forename: Abbas
authors.initials: A
authors.lastname: Kaffashi
authors.affiliation: c Basic Pharmaceutical Sciences Department.
authors.forename: Semih
authors.initials: S
authors.lastname: Çalamak
authors.affiliation: c Basic Pharmaceutical Sciences Department.
authors.forename: Kezban
authors.initials: K
authors.lastname: Ulubayram
authors.affiliation: d Pharmaceutical Chemistry Department , and.
authors.forename: Erhan
authors.initials: E
authors.lastname: Palaska
authors.affiliation: e Ophthalmology Department, Faculty of Medicine, Hacettepe University , Ankara , Turkey.
authors.forename: Hasan Basri
authors.initials: HB
authors.lastname: Çakmak
authors.affiliation: a Pharmaceutical Technology Department, Faculty of Pharmacy.
authors.forename: Nurşen
authors.initials: N
authors.lastname: Ünlü
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003315:Cornea / Q000378:metabolism*; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014018:Tissue Distribution
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016572:Cyclosporine
keywords: Cyclosporin A; in vivo; nanoparticle; ocular drug delivery; ocular implant