title: In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan.
abstract: Gellan gum, kappa-carrageenan and alginates are natural polysaccharides able to interact with different cations that can be used to elaborate ion-activated in situ gelling systems for different uses. The interaction between fluid solutions of these polysaccharides and cations presents into the tear made these biopolymers very interesting to elaborate ophthalmic drug delivery systems. The main purpose of this study is to evaluate the ability of mixtures of these polymers to obtain ion-activated ophthalmic in situ gelling systems with optimal properties for ocular use. To achieve this purpose different proportion of the biopolymers were analyzed using a mixture experimental design evaluating their transparency, mechanical properties and bioadhesion in the absence and presence of simulated tear fluid. Tear induces a rapid sol-to-gel phase transition in the mixtures forming a consistent hydrogel. The solution composed by 80% of gellan gum and 20% kappa-carrageenan showed the best mechanical and mucoadhesive properties. This mixture was evaluated for rheological behavior, microstructure, cytotoxicity, acute corneal irritancy, ex-vivo and in vivo ocular toxicity and in vivo corneal contact time using Magnetic Resonance Images (MRI) techniques. Result indicates that the system is safe at ophthalmic level and produces an extensive ocular permanence higher than 6h.
authors.affiliation: Pharmacy and Pharmaceutical Technology Department and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela 15782, Spain; Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Anxo
authors.initials: A
authors.lastname: Fernández-Ferreiro
authors.affiliation: Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: González Barcia
authors.affiliation: Instituto Oftalmológico Gómez-Ulla, Rúa de Maruxa Mallo, 3, Santiago de Compostela 15706, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gil-Martínez
authors.affiliation: Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Vieites-Prado
authors.affiliation: Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain; Surgery Department (Ophthalmology), Faculty of Optics and Optometry, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela 15782, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Lema
authors.affiliation: Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Barbara
authors.initials: B
authors.lastname: Argibay
authors.affiliation: Pharmacy and Pharmaceutical Technology Department and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela 15782, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Blanco Méndez
authors.affiliation: Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Lamas
authors.affiliation: Pharmacy and Pharmaceutical Technology Department and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela 15782, Spain. Electronic address: francisco.otero@usc.es.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Otero-Espinar
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D002351:Carrageenan / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002645:Chickens; D016503:Drug Delivery Systems / Q000379:methods*; D005123:Eye / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D015603:Keratinocytes / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008855:Microscopy, Electron, Scanning; D044367:Phase Transition; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D012212:Rheology; D013499:Surface Properties; D013666:Tears / Q000737:chemistry
chemical_list: D020100:Hydrogels; D011135:Polysaccharides, Bacterial; C048288:gellan gum; D002351:Carrageenan
keywords: Alginate (CID 6850754); Gellan gum; Gellan-gum (CAS Number 71010-52-1); Het-Cam; In situ gelling system; In vivo ocular surface permanence; Ion-activated ophthalmic hydrogel; Kappa-carrageenan; Kappa-carrageenan (CID 11966249); Magnetic Resonance Imaging; Ocular toxicity; Polysaccharides; Real-Time Cell Analyzer System