title: In vivo eye surface residence determination by high-resolution scintigraphy of a novel ion-sensitive hydrogel based on gellan gum and kappa-carrageenan.
abstract: In last years, sensitive hydrogels have become a breakthrough in ophthalmic pharmaceutical technology aimed at developing new strategies to increase the residence time of active substances. In a previous paper, we qualitatively demonstrated the capacity of a new ion sensitive hydrogel to increase the residence time. Nevertheless, the clearance of the gel from the ocular surface was not quantifiable with the used methodology. The aim of the present work was to use a well-established approach based on scintigraphy to quantitatively estimate the residence time of the previously proposed hydrogel. The rat corneal residence time of a topic ophthalmic formulation containing gellan gum and kappa carragenan (0.82% w/v) labeled with99mTc-DTPA radiotracer was evaluated and compared with the residence of an aqueous solution. Ophthalmic safety studies such as eye irritation or passage through the cornea were also carried out. After 1.5h of contact, 77% of the hydrogel remained in the ocular surface, presenting kinetics of disappearance one-phase decay and a half time of 262min. We conclude that the novel ophthalmic hydrogel developed with kappa carrageenan and gellan gum remains for long periods of time on the corneal surface, presenting a drop that fits an exponential decay.
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; Molecular Imaging Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, University Clinical Hospital, Universidade de Santiago de Compostela, 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: Molecular Imaging Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Silva-Rodríguez
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: Francisco Javier
authors.initials: FJ
authors.lastname: Otero-Espinar
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, University Clinical Hospital, Universidade de Santiago de Compostela, 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: Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Lamas
authors.affiliation: Molecular Imaging Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain; Nuclear Medicine Department, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Molecular Imaging Group, Department of Radiology, Faculty of Medicine, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela 15782, Spain; Fundación Tejerina, Madrid 28003, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Ruibal
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: Andrea
authors.initials: A
authors.lastname: Luaces-Rodríguez
authors.affiliation: Clinical Neurosciences Research Laboratory, University Clinical Hospital, Universidade de Santiago de Compostela, 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, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Lema
authors.affiliation: Molecular Imaging Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain; Nuclear Medicine Department, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Michel
authors.initials: M
authors.lastname: Herranz
authors.affiliation: Molecular Imaging Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Gómez-Lado
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-Mendez
authors.affiliation: Ophthalmology Department, Xerencia de Xestión Integrada de Santiago de Compostela (SERGAS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gil-Martínez
authors.affiliation: Obesidomic Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Pardo
authors.affiliation: Molecular Imaging Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Alexis
authors.initials: A
authors.lastname: Moscoso
authors.affiliation: Molecular Imaging Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain; Nuclear Medicine Department, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Galician PET Radiopharmacy Unit, Galaria, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sánchez-Martínez
authors.affiliation: Molecular Imaging Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain; Medical Physics Department, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain. Electronic address: juan.pardo.montero@sergas.es.
authors.forename: Juan
authors.initials: J
authors.lastname: Pardo-Montero
authors.affiliation: Molecular Imaging Group, University Clinical Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain; Molecular Imaging Group, Department of Radiology, Faculty of Medicine, University of Santiago de Compostela (USC), Campus Vida, Santiago de Compostela 15782, Spain. Electronic address: pablo.aguiar.fernandez@sergas.es.
authors.forename: Pablo
authors.initials: P
authors.lastname: Aguiar
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000009:adverse effects / Q000737:chemistry*; D003315:Cornea / Q000000981:diagnostic imaging / Q000378:metabolism*; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D020100:Hydrogels / Q000009:adverse effects / Q000737:chemistry*; D007509:Irritants; D007553:Isotope Labeling; D008297:Male; D009883:Ophthalmic Solutions; D011135:Polysaccharides, Bacterial / Q000009:adverse effects / Q000737:chemistry*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005079:Excipients; D020100:Hydrogels; D007509:Irritants; D009883:Ophthalmic Solutions; D011135:Polysaccharides, Bacterial; D019275:Radiopharmaceuticals; C048288:gellan gum; D002351:Carrageenan
keywords: (99m)Tc-DTPA; Cell cytotoxicity; Gellan-Gum (CAS Number 71010-52-1); Het Cam; Ion sensitive hydrogel; Kappa-Carrageenan (CID: 11966249); Ocular pharmacokinetics; Ophthalmic formulations; Radiotracers; Scintigraphy; Technetium-99mTc (CID: 26476); Technetium-99mTc-DTPA (CID: 166744)