4.8 Article

Porous poly(ε-caprolactone) implants: A novel strategy for efficient intraocular drug delivery

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 316, Issue -, Pages 331-348

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2019.09.023

Keywords

Poly (epsilon-caprolactone); Biodegradable porous implants; Supercritical carbon dioxide foaming/mixing method; Intraocular drug delivery; Safety; Retina

Funding

  1. FCT, Portugal [PD/BD/114115/2015, PD/BD/127821/2016, SFRH/BPD/101048/2014, PTDC/NEU-OSD/3123/2014, UID/NEU/04539/2013, PEst-C/EQB/UI0102/2013, PEst-C/EQB/UI0102/2018, PEst-C/EQB/UI0102/2019]
  2. FEDER-COMPETE [FCOMP-010124-FEDER-028417, POCI-01-0145-FEDER-007440]
  3. Centro 2020 Regional Operational Programme [CENTRO-01-0145-FEDER000008: Brain Health 2020]
  4. Fundação para a Ciência e a Tecnologia [PD/BD/127821/2016, PD/BD/114115/2015, PTDC/NEU-OSD/3123/2014] Funding Source: FCT

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This work reports the development of porous poly (epsilon-caprolactone) (PCL)-based intraocular implants, prepared by green supercritical carbon dioxide (scCO(2)) foaming/mixing method (SFM), to produce implants that degrade faster than typical slow-degrading PCL-based implants. The higher porosities and surface areas of these implants led to faster degradation rates at in vitro accelerated alkaline conditions than low porosity/surface area implants prepared by hot melting processing. These porous implants also presented distinct (faster) release rates of a test-drug (dexamethasone). Additionally, these porous devices did not cause cell death and did not reduce the number of neurons, indicating that are not toxic to retinal cells. We further explored the impact of PCL-based implant to the retina by in vivo evaluation and histological analysis. Implants were surgically inserted in the vitreous of Wistar rats, and their presence did not change the function, structure and anatomy of the retina. These devices demonstrated a good intraocular tolerance, further confirming their viability for prolonged drug delivery applications. Further comprehensive studies based on this promising preliminary assessment and proofof-concept could enable its future translation to clinical protective strategies for retinal diseases.

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