Dexamethasone delivery to the ocular posterior segment by sustained-release Laponite formulation

Prieto, E. ; Cardiel, M.J. (Universidad de Zaragoza) ; Vispe, E. ; Idoipe, M. ; Garcia-Martin, E. (Universidad de Zaragoza) ; Fraile, J.M. (Universidad de Zaragoza) ; Polo, V. (Universidad de Zaragoza) ; Mayoral, J.A. (Universidad de Zaragoza) ; Pablo, L.E. (Universidad de Zaragoza) ; Rodrigo, M.J.

Resumen: This paper presents a novel nanoformulation for sustained-release delivery of dexamethasone (DEX) to the ocular posterior segment using a Laponite (LAP) carrier - DEX/LAP 1:10 w w-1 formulation; 10 mg ml-1. In vivo ocular feasibility and pharmacokinetics after intravitreal (IV) and suprachoroidal (SC) administration in rabbit eyes are compared against IV administration of a DEX solution (1 mg ml-1). Thirty rabbit eyes were injected with the DEX/LAP formulation (15 suprachoroid/15 intravitreous). Ophthalmological signs were monitored at day 1 and at weeks 1-4-12-24 post-administration. Three eyes per sample time point were used to quantify DEX concentration using high-performance liquid chromatography-mass spectrometry. The ocular tissues'' pharmacokinetic parameters (lens, vitreous humour, choroid-retina unit and sclera) were studied. DEX/LAP was well tolerated under both administration methods. Peak intraocular DEX levels from the DEX/LAP were detected in the vitreous humour after both deliveries soon after administration. The vitreous area under the curve was significantly greater after both DEX/LAP deliveries (IV: 205 968.47; SC: 11 442.22 ng g-1 d-1) than after IV administration of the DEX solution (317.17 ng g-1 d-1). Intravitreal DEX/LAP delivery extended higher vitreous DEX levels up to week 24 (466.32 311.15 ng g-1). With SC delivery, DEX levels were detectable in the choroid-retina unit (12.04 20.85 ng g-1) and sclera (25.46 44.09 ng g-1) up to week 24. This study demonstrated the intraocular feasibility of both SC and IV administration of the DEX/LAP formulation. The LAP increased the intraocular retention time of DEX when compared with conventional solutions. DEX/LAP could be considered a biocompatible and useful sustained-release formulation for treating posterior-pole eye diseases.

Idioma: Inglés

DOI: 10.1088/1748-605X/aba445

Año: 2020

Publicado en: Biomedical Materials 15, 6 (2020), 065021 [14 pp]
ISSN: 1748-6041

Factor impacto JCR: 3.715 (2020)

Categ. JCR: ENGINEERING, BIOMEDICAL rank: 39 / 90 = 0.433 (2020) - Q2 - T2
Categ. JCR: MATERIALS SCIENCE, BIOMATERIALS rank: 24 / 40 = 0.6 (2020) - Q3 - T2

Factor impacto SCIMAGO: 0.743 - Bioengineering (Q1) - Biomaterials (Q1) - Mechanics of Materials (Q1) - Business and International Management (Q1) - Chemistry (miscellaneous) (Q1) - Biomedical Engineering (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/E37-17R
Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/Construyendo Europa desde Aragón
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/M17-00213
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI12-02285
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI17-01726
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI17-01946
Financiación: info:eu-repo/grantAgreement/ES/MINECO-AEI-FEDER/MAT2017-83858-C2-2

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)
Área (Departamento): Área Oftalmología (Dpto. Cirugía)
Área (Departamento): Área Anatomía Patológica (Dpto. Cirugía)