Poster presented at the 4th Congress on Innovation in Drug Delivery Site-Specific Drug Delivery (IDD2016). Antibes-Juan-les-Pins, France, 25-28 September 2016N/

Colaço, Rogério

Filipe, Helena

Mata, José L. G.

Pereira, José C. F.

Pereira, José M. C.

Pimenta, Andreia

Saramago, Benilde

Serro, Ana Paula

Valente, Ana

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 Ocular drug delivery from contact lenses:  mimetizing the hydrodynamic conditions of the eye  Andreia Pimenta1,2, Ana Valente1, José M.C Pereira2, José C.F Pereira2, Helena Filipe3,4, José L.G. Mata1, Rogério Colaço2, Benilde Saramago1, Ana Paula Serro1,5   1 Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal 2 Departamento de Engenharia Mecânica e IDMEC, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal 3 Hospital das Forças Armadas - Polo de Lisboa, Lisbon, Portugal 4 Hospital dos SAMS, Lisbon, Portugal 5 Centro de Investigação Interdisciplinar Egas Moniz, Instituto Superior de Ciências da Saúde Egas Moniz, Caparica, Portugal . To Fundação para a Ciência e a Tecnologia for Andreia Pimenta PhD grant BD/52334/2013 (MIT-Portugal program) and for funding through projects UID/QUI/00100/2013 and M-ERA.NET/0005/2012. Acknowledgments  Currently, most in vitro drug release studies for ophthalmic applications are carried out in static sink conditions. Although this procedure is simple and useful to make comparative studies, it does not describe adequately the drug release kinetics in the eye, considering the small tear volume and flow rates found in vivo. In a normal situation, the human eye contains a tear volume that ranges from 6.2 to 30.0 L [1] and the tear flow rate assumes values between 0.9 and 2.1 L/min [2]. The use of contact lenses increases the tear turnover to values of the order 1.4-4.3 L/min [2]. Introduction  Microfluidic cell (MFC)  A MFC of poly(methylmethacrylate) with a cylindrical inner chamber of 45 µL  was designed and fabricated.        The flow inside the microfluidic cell was modeled through the numerical solution of the Navier-Stokes and continuity equations using the Star-CCM+ simulation package.  Drug release experiments - Static: Diclofenac loaded 2-hydroxyethyl methacrylate  (PHEMA) samples were immersed in 4 mL of PBS solution in closed vessels, at 36 °C, under stirring (180 rpm). At predetermined time intervals, 800 µl aliquots of the supernatant were collected and replaced by the same volume of fresh PBS solution.  - Dynamic: drug release experiments in the microfluidic cell were performed at 36°C and a continuous flow of PBS of 3 µL/min.  In vivo efficacy The in vivo efficacy of anti-inflammatory released in dynamic conditions was estimated through comparison to the daily dose delivered by topical application. Methods Results  A microfluidic cell was successfully fabricated to approximate in vitro ocular drug release experiments to the eye tear film in vivo hydrodynamic conditions.  Experimental results shown that DCF release kinetics is affected by the release conditions; dynamic conditions developed in this study are expected to be closer to the in vivo conditions when compared with common sink conditions.  Results suggest the studied drug/hydrogel pair shall be effective during  5 days.  Conclusions [1] Mishima S, Gasset A, Klyce SD, Baum JL, Determination of tear volume and tear flow. Invest Ophthalmol Vis Sci. 1966;5: 264–76. [2] Robert L. Stamper, Marc F. Lieberman MVD, Becker-Shaffer’s Diagnosis and Therapy of the Glaucomas. Elsevier, 8th Edition.   i) Design and validation of a microfluidic cell to mimic the continuous, volumetric flow rate of tear fluid and its low volume; ii) Comparison of drug release profiles of anti-inflammatory, diclofenac (DCF), from a soft contact lens material obtained in static sink and in dynamic conditions; iii) Estimation of the drug released in vivo efficacy. Objectives Figure 1.  a) Schematic design of the MFC b) Experimental apparatus Figure 4.  DCF concentration Day DCF mass (µg/lens) 1 420.0 2 127.7 3 54.0 4 22.8 5 9.7 6 3.6 Table 1. Amount of DCF released from PHEMA , estimated by numerical simulation  MFC inner chamber with volume of 45 µL.  Considering a flow rate of 3µL/min, the fluid flows in the cell uniformly (Figure 2). Symmetric and very regular paths are followed from the inlet pipe to the eight exiting pipes.  Possibility of numerically simulate other inner chamber volumes and flow rates. Figure 2. Representation of the fluid paths inside the microfluidic cell Author contact: andreia.pimenta@tecnico.ulisboa.pt Figure 3.  DCF fractional cumulative mass release  Different release kinetics for the same drug/hydrogel pair. . 3 mL . 45 µL . Continuous flow  From the release results in dynamic conditions it is possible to estimate the concentration of DCF released from PHEMA hydrogels in a volume equivalent to the tear film. Considering that…. The recommend posology for DCF is 8.5 µg/day (5 x 1 drop).  Results suggest the studied drug/hydrogel pair shall be effective during  5 days.  Drug eluting contact lens Human eye   In order to predict in a more reliable way the drug release kinetics in the eye, it is crucial to develop microfluidic models that mimic, as close as possible, the hydrodynamic conditions of the eye.  

Ocular drug delivery from contact lenses: mimetizing the hydrodynamic conditions of the eye

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Ocular drug delivery from contact lenses: mimetizing the hydrodynamic conditions of the eye

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