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Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology

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Andrés-Guerrero, Vanessa, Zong, Mengmeng, Ramsay, Eva, Rojas, Blanca, Sarkhel, Sanjay, Gallego, Beatriz, de Hoz, Rosa, Ramírez, Ana I., Salazar, Juan José, Triviño, Alberto, Ramírez, José M., del Amo, Eva M., Cameron, Neil R., de-las-Heras, Beatriz, Urtti, Arto, Mihov, George, Dias, Aylvin and Herrero-Vanrell, Rocío (2015) Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology. Journal of Controlled Release, 211 . pp. 105-117. doi:10.1016/j.jconrel.2015.05.279

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Official URL: http://dx.doi.org/10.1016/j.jconrel.2015.05.279

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Abstract

Most 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.

Item Type: Journal Article
Subjects: R Medicine > RE Ophthalmology
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Science > Engineering
Library of Congress Subject Headings (LCSH): Ophthalmic drugs , Eye -- Diseases -- Treatment, Microspheres, Polymeric drug delivery systems
Journal or Publication Title: Journal of Controlled Release
Publisher: Elsevier BV
ISSN: 0168-3659
Official Date: 10 August 2015
Dates:
DateEvent
10 August 2015Published
21 May 2015Available
19 May 2015Accepted
Volume: 211
Page Range: pp. 105-117
DOI: 10.1016/j.jconrel.2015.05.279
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Seventh Framework Programme (European Commission) (FP7)
Grant number: Project number 246180
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