Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology

Vanessa Andres-Guerrero, Mengmeng Zong, Eva Ramsay, Blanca Rojas, Sanjay Sarkhel, Beatriz Gallego, Rosa de Hoz, Ana I. Ramirez, Juan Jose Salazar, Alberto Trivino, Jose M. Ramirez, Eva M. del Amo, Neil Cameron, Beatriz de-las-Heras, Arto Urtti, George Mihov, Aylvin Dias, Rocio Herrero-Vanrell

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87 Citations (Scopus)

Abstract

Most of the posterior segment diseases are chronic and multifactorial and require long-termintraocular 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 presentwork involves the description of a newgeneration of microspheres based on poly(ester amide)s (PEA), which are novel polymerswith 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 inmale Sprague–Dawley rats and the location of themicrospheres 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.
Original languageEnglish
Pages (from-to)105 - 117
Number of pages13
JournalJournal of Controlled Release
Volume211
DOIs
Publication statusPublished - 2015

Keywords

  • Ocular drug delivery
  • Microspheres
  • Poly(ester amide)
  • Tolerance
  • Dexamethasone
  • Intraocular injection

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