title: Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration.
abstract: Successful therapy for chronic diseases affecting the posterior segment of the eye requires sustained drug concentrations at the site of action for extended periods of time. To achieve this, it is necessary to use high systemic doses or frequent intraocular injections, both associated with serious adverse effects. In order to avoid these complications and improve patient's quality of life, an experimental study has been conducted on the preparation of a new generation of biodegradable poly(D,L-lactide-co-glycolide) (50:50) (PLGA) polymer microspheres (MSs) loaded with Dxm, vitamin E and/or human serum albumin (HSA). Particles were prepared according to a S/O/W encapsulation method and the 20-40μm fraction was selected. This narrow size distribution is suitable for minimally invasive intravitreal injection by small calibre needles. Characterisation of the MSs showed high Dxm loading and encapsulation efficiency (> 90%) without a strong interaction with the polymer matrix, as revealed by DSC analysis. MSs drug release studies indicated a small burst effect (lower than 5%) during the first five hours and subsequently, drug release was sustained for at least 30days, led by diffusion and erosion mechanisms. Dxm release rate was modulated when solid state HSA was incorporated into MSs formulation. SDS-PAGE analysis showed that the protein maintained its integrity during the encapsulation process, as well as for the release study. MSs presented good tolerance and lack of cytotoxicity in macrophages and HeLa cultured cells. After 12months of storage under standard refrigerated conditions (4±1°C), MSs retained appropriate physical and chemical properties and analogous drug release kinetics. Therefore, we conclude that these microspheres are promising pharmaceutical systems for intraocular administration, allowing controlled release of the drug.
authors.affiliation: Departamento de Ciencias Biomédicas, Unidad docente de Farmacia y Tecnología Farmacéutica, Universidad de Alcalá, Ctra. Madrid-Barcelona (A2) Km. 33. 600, 28871, Alcalá de Henares (Spain).
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez Villanueva
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Universidad Complutense de Madrid, Plaza de Ramón y Cajal, 28040, Madrid (Spain).
authors.forename: Irene
authors.initials: I
authors.lastname: Bravo-Osuna
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Universidad Complutense de Madrid, Plaza de Ramón y Cajal, 28040, Madrid (Spain).
authors.forename: Rocío
authors.initials: R
authors.lastname: Herrero-Vanrell
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Universidad Complutense de Madrid, Plaza de Ramón y Cajal, 28040, Madrid (Spain).
authors.forename: Irene Teresa
authors.initials: IT
authors.lastname: Molina Martínez
authors.affiliation: Departamento de Ciencias Biomédicas, Unidad docente de Farmacia y Tecnología Farmacéutica, Universidad de Alcalá, Ctra. Madrid-Barcelona (A2) Km. 33. 600, 28871, Alcalá de Henares (Spain). Electronic address: manuel.guzman@uah.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Guzmán Navarro
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D005938:Glucocorticoids / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D058449:Intravitreal Injections; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012709:Serum Albumin / Q000737:chemistry; D014810:Vitamin E / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D012709:Serum Albumin; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone
keywords: Controlled release; Dexamethasone; Human serum albumin; Intraocular administration; Microspheres; PLGA; Stability