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

Research output: Contribution to journalArticleResearchpeer-review

53 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

Cite this

Andres-Guerrero, V., Zong, M., Ramsay, E., Rojas, B., Sarkhel, S., Gallego, B., ... Herrero-Vanrell, R. (2015). Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology. Journal of Controlled Release, 211, 105 - 117. https://doi.org/10.1016/j.jconrel.2015.05.279
Andres-Guerrero, Vanessa ; Zong, Mengmeng ; Ramsay, Eva ; Rojas, Blanca ; Sarkhel, Sanjay ; Gallego, Beatriz ; Hoz, Rosa de ; Ramirez, Ana I. ; Salazar, Juan Jose ; Trivino, Alberto ; Ramirez, Jose M. ; del Amo, Eva M. ; Cameron, Neil ; de-las-Heras, Beatriz ; Urtti, Arto ; Mihov, George ; Dias, Aylvin ; Herrero-Vanrell, Rocio. / Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology. In: Journal of Controlled Release. 2015 ; Vol. 211. pp. 105 - 117.
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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.",
keywords = "Ocular drug delivery, Microspheres, Poly(ester amide), Tolerance, Dexamethasone, Intraocular injection",
author = "Vanessa Andres-Guerrero and Mengmeng Zong and Eva Ramsay and Blanca Rojas and Sanjay Sarkhel and Beatriz Gallego and Hoz, {Rosa de} and Ramirez, {Ana I.} and Salazar, {Juan Jose} and Alberto Trivino and Ramirez, {Jose M.} and {del Amo}, {Eva M.} and Neil Cameron and Beatriz de-las-Heras and Arto Urtti and George Mihov and Aylvin Dias and Rocio Herrero-Vanrell",
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Andres-Guerrero, V, Zong, M, Ramsay, E, Rojas, B, Sarkhel, S, Gallego, B, Hoz, RD, Ramirez, AI, Salazar, JJ, Trivino, A, Ramirez, JM, del Amo, EM, Cameron, N, de-las-Heras, B, Urtti, A, Mihov, G, Dias, A & Herrero-Vanrell, R 2015, 'Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology', Journal of Controlled Release, vol. 211, pp. 105 - 117. https://doi.org/10.1016/j.jconrel.2015.05.279

Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology. / Andres-Guerrero, Vanessa; Zong, Mengmeng; Ramsay, Eva; Rojas, Blanca; Sarkhel, Sanjay; Gallego, Beatriz; Hoz, Rosa de; Ramirez, Ana I.; Salazar, Juan Jose; Trivino, Alberto; Ramirez, Jose M.; del Amo, Eva M.; Cameron, Neil; de-las-Heras, Beatriz; Urtti, Arto; Mihov, George; Dias, Aylvin; Herrero-Vanrell, Rocio.

In: Journal of Controlled Release, Vol. 211, 2015, p. 105 - 117.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology

AU - Andres-Guerrero, Vanessa

AU - Zong, Mengmeng

AU - Ramsay, Eva

AU - Rojas, Blanca

AU - Sarkhel, Sanjay

AU - Gallego, Beatriz

AU - Hoz, Rosa de

AU - Ramirez, Ana I.

AU - Salazar, Juan Jose

AU - Trivino, Alberto

AU - Ramirez, Jose M.

AU - del Amo, Eva M.

AU - Cameron, Neil

AU - de-las-Heras, Beatriz

AU - Urtti, Arto

AU - Mihov, George

AU - Dias, Aylvin

AU - Herrero-Vanrell, Rocio

PY - 2015

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N2 - 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.

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KW - Ocular drug delivery

KW - Microspheres

KW - Poly(ester amide)

KW - Tolerance

KW - Dexamethasone

KW - Intraocular injection

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JO - Journal of Controlled Release

JF - Journal of Controlled Release

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