Andrés Guerrero, VanessaZong, MengmengRamsay, EvaRojas López, BlancaSarkhel, SanjayGallego Collado, Beatriz IsabelHoz Montañana, Rosa deRamírez Sebastián, Ana IsabelSalazar Corral, Juan JoséTriviño Casado, AlbertoRamirez Sebastian, Jose ManuelAmo, Eva M. delCameron, NeilLas Heras Polo, Beatriz deUrtti, ArtoMihov, GeorgeDias, AylvinHerrero Vanrell, Rocío2023-06-182023-06-182015-08-100168-365910.1016/j.jconrel.2015.05.279https://hdl.handle.net/20.500.14352/23243Received 3 March 2015, Revised 18 May 2015, Accepted 19 May 2015, Available online 21 May 2015Most of the posterior segment diseases are chronic and multifactorial and require long-term intraocular medication. Conventional treatments of these pathologies consist of successive intraocular injections, which are associated with adverse effects. Successful therapy requires the development of new drug delivery systems able to release the active substance for a long term with a single administration. The present work involves the description of a new generation of microspheres based on poly(ester amide)s (PEA), which are novel polymers with improved biodegradability, processability and good thermal and mechanical properties. We report on the preparation of the PEA polymer, PEA microspheres (PEA Ms) and their characterization. PEA Ms (~ 15 μm) were loaded with a lipophilic drug (dexamethasone) (181.0 ± 2.4 μg DX/mg Ms). The in vitro release profile of the drug showed a constant delivery for at least 90 days. Based on the data from a performed in vitro release study, a kinetic ocular model to predict in vivo drug concentrations in a rabbit vitreous was built. According to the pharmacokinetic simulations, intravitreal injection of dexamethasone loaded PEA microspheres would provide release of the drug in rabbit eyes up to 3 months. Cytotoxicity studies in macrophages and retinal pigment epithelial cells revealed a good in vitro tolerance of the microsystems. After sterilization, PEA Ms were administered in vivo by subtenon and intravitreal injections in male Sprague–Dawley rats and the location of the microspheres in rat eyes was monitored. We conclude that PEA Ms provide an alternative delivery system for controlling the delivery of drugs to the eye, allowing a novel generation of microsphere design.engjournal articlehttps://doi.org/10.1016/j.jconrel.2015.05.279http://www.sciencedirect.com/science/article/pii/S0168365915005787restricted access547.1615.457617.73/.74Ocular drug deliveryMicrospheresPoly(ester amide)ToleranceDexamethasoneIntraocular injectionQuímica orgánica (Química)Farmacología (Medicina)Oftalmología2306 Química Orgánica3201.09 Oftalmología