July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018

Drug-loaded intraocular lenses: prediction of the in vivo therapeutic efficacy
Author Affiliations & Notes
  • Helena Filipe
    Ophthalmology, Hospital of the Armed Forces, Lisbon, Portugal
    Ophthalmology, Hospital SAMS, Lisbon, Portugal
  • Ana Topete
    Instituto Superior Técnico, Lisbon, Portugal
  • Benilde Saramago
    Instituto Superior Técnico, Lisbon, Portugal
  • Ana Paula Serro
    Instituto Superior Técnico, Lisbon, Portugal
    Instituto Superior de Ciências da Saúde Egas Moniz, Lisbon, lisbon, Portugal
  • Footnotes
    Commercial Relationships   Helena Filipe, None; Ana Topete, None; Benilde Saramago, None; Ana Paula Serro, None
  • Footnotes
    Support  Fundação para a Ciência e Tecnologia (FCT) [projects UID/QUI/00100/2013 and PTDC/CTM-BIO/3640/2014] ; support from PhysIOL for providing the materials for IOLs
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4455. doi:
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    • Get Citation

      Helena Filipe, Ana Topete, Benilde Saramago, Ana Paula Serro;
      Drug-loaded intraocular lenses: prediction of the in vivo therapeutic efficacy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4455.

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

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Abstract

Purpose : Cataracts treatment involves the removal of the opacified natural lens and implantation of an intraocular lens (IOL). In the post-operatory period, antibiotics and anti-inflammatories eye drops are administered with a frequent posology to prevent eventual complications. This drug delivery method is not very effective and may lead to low patient compliance. In this work it is explored the possibility of using drug-loaded IOLs to comply with the therapeutic needs: 1-2 weeks for antibiotic and 3-4 weeks for anti-inflammatory. A simplified mathematical model was used to predict the in vivo efficacy of the devices, by comparing the estimated drug concentration in the aqueous humour with values reported in the literature for the minimal inhibitory concentration (MIC) of the antibiotic and half-maximal inhibitory concentrations (IC50) for cyclooxygenase-1 and 2 (COX-1 and COX2) for anti-inflammatories.

Methods :
An antibiotic, moxifloxacin (MXF), and 2 anti-inflammatories, diclofenac (DFN) and ketorolac (KTL), were loaded in the IOLs by soaking, in the drugs solutions at 60°C for 2 weeks. Drug release experiments in vitro were performed in sink conditions. A mathematical model that takes into account the volume of the aqueous humour and its rate of renovation was fitted to the experimental release profiles using the equation of Korsmeyer-Peppas for the first points (≤60% of the total drug release amount) and Table Curve® software for the remaining points, to predict the in vivo efficacy of the drugs. Direct comparison with aqueous humour drug concentrations reported in vivo tests was also carried out.

Results :
Controlled release profiles for more than 20 days for MXF, around 15 days for DFN and 10 days for KTL were obtained in the in vitro experiments. According to the model, MXF shall be above or within the MICs ranges for S. aureus and S. epidermidis for 2 weeks, DFN above the ranges of IC50 for COX-1 and COX-2 for 4 weeks, and KTL above the minimum value for 2 weeks only. Comparing with aqueous humour drug concentrations found in literature, MXF concentration is above the minimum value for more than 2 weeks, DFN for 4 weeks and KTL for 18 days. All estimated maximum concentrations shall be non-toxic for the eye.

Conclusions :
MXF and DFN comply with the therapeutic needs, while KTL is slightly under.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 


Figure 1. Estimated [MXF] in the aqueous humor: A) first 24 h, (B) last 6-15 days


Figure 1. Estimated [MXF] in the aqueous humor: A) first 24 h, (B) last 6-15 days

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