May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Dexamethasone-Loaded Poly--Caprolactone Intravitreal Implants
Author Affiliations & Notes
  • F. Azan
    Ophthalmology, Hotel Dieu Paris, Paris, France
    U598; Physiopathology of ocular diseases : Therapeutic innovations, Inserm, Paris, France
  • S. Fialho
    U598; Physiopathology of ocular diseases : Therapeutic innovations, Inserm, Paris, France
    Faculty of Pharmacy, Federal University, Minas Gerais, Brazil
  • A. Silva-Cunha
    U598; Physiopathology of ocular diseases : Therapeutic innovations, Inserm, Paris, France
    Faculty of Pharmacy, Federal University, Minas Gerais, Brazil
  • J.-L. Bourges
    Ophthalmology, Hotel Dieu Paris, Paris, France
    U598; Physiopathology of ocular diseases : Therapeutic innovations, Inserm, Paris, France
  • F. Behar-Cohen
    Ophthalmology, Hotel Dieu Paris, Paris, France
    U598; Physiopathology of ocular diseases : Therapeutic innovations, Inserm, Paris, France
  • Footnotes
    Commercial Relationships F. Azan, None; S. Fialho, None; A. Silva-Cunha, None; J. Bourges, None; F. Behar-Cohen, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 284. doi:
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    • Get Citation

      F. Azan, S. Fialho, A. Silva-Cunha, J.-L. Bourges, F. Behar-Cohen; Dexamethasone-Loaded Poly--Caprolactone Intravitreal Implants. Invest. Ophthalmol. Vis. Sci. 2007;48(13):284.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: poly-ε-caprolactone (PCL) is a biodegradable and biocompatible polymer that presents a very low degradation rate, making it suitable for long-term delivery of drugs. While extensive work has been conducted for its medical applications, few studies have explored its potential for intraocular sustained drug delivery. The objective of the present work is to evaluate the feasibility and characteristics of PCL tablets for the prolonged and controlled intravitreous release of dexamethasone.

Methods:: Dexamethasone crystalline (MW = 392.5; aqueous solubility at 37°C = 1.0 mg/ml) and polymer poly-ε-caprolactone (PCL, density = 1.145 g/cm3) were purchased from Sigma-Aldrich CO (France). For the implant preparation, dexamethason and PCL (1:4) were dissolved in a mixture of acetonitrile and distilled water and placed at -80 oC. The frozen solution was lyophilized and 200 mg of the obtained powder was compressed using a hydraulic press SSP-10A at 10 ton/cm2, during 10 minutes in the form of discs containing a diameter of 13 mm. The obtained discs were, next, cut in the size of implants of 4.0 mm of diameter. The in vitro release study was realized under sink conditions and the mass loss was evaluated in parallel. Morphological changes of the implants were analyzed using scanning electron microscopy and differential scanning calorimetry (DSC) was used to check dexamethasone and PCL stability. In vivo tolerance was evaluated after implantation of empty (n=3) and dexamethasone-loaded PCL implants (N=3) in pigmented rabbit eyes. Rabbit eyes were followed-up at 3, 8, 15 and 30 days post implantation.

Results:: Implant allows for a controlled and prolonged delivery of dexamethasone since it releases 25% of dexamethasone in 21 weeks under sink conditions. Its very low degradation rate was confirmed by the mass loss and scanning electron microscopy studies. It is possible to consider that the developed implant can release the drug, in vitro, for more than one year. In vivo studies are currently undertaken to correlate the release profile. Preliminary observations show that PCL intravitreous implants are very well tolerated in the rabbit eye.

Conclusions:: PCL intravitreous implants are well tolerated and allows for a very long controlled release of drugs.

Keywords: corticosteroids • vitreous • drug toxicity/drug effects 
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