In silico model of antibiotics and quorum inhibitors sustained release from the multilayer corneal patch for the microbial keratitis treatment

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ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków


Kijeńska-Gawrońska, Ewa (Faculty of Materials Science and Engineering, Warsaw University of Technology, ul. Wołoska 141, 02-507, Warsaw)


Microbial keratitis is a devastating vision-threatening ocular disease requiring immediate broad spectrum antimicrobial treatment to prevent scarring, corneal perforation, and/or endophthalmitis. In the progression stages, to reduce the burden on the immune system, keratoplasty is applied. Temporary patches usually are used until the microbial activity is over in order to preserve tissue integrity until transplantation of a complete corneal graft is possible. Antibiotic-enhanced drops are often put into the eye until the microbial activity stops. However, with the effect of tears, antibiotics are almost removed from the eye within a few minutes.
The novel strategy aims to incorporate drugs inside synthetic tectonic patches, what can enable for reducing the amount of antibiotics by suturing patches to the infected zone and releasing agents directly to the targeted cornea perforation infected area. It is also aimed to use quorum sensing (QS) inhibitors to stop the virulence of bacterial and fungal-based keratitis. Utilization of in silico methods may lead to effective designing and development of the multilayer patches with optimal parameters in terms of structure and composition.
A computational model predicting the kinetics of drugs released from particular layers of the designed corneal patch was developed. The model was based on the rabbit eyeball geometry. The model assumes the diffusional character of the drug transport, where the drug clearance is caused mainly by the aqueous humor drainage. Due to the above-mentioned fact, the vitreous body was ignored in the developed model. The aqueous humor drainage was predicted by computer fluid dynamics (CFD) modeling. The developed in silico model enables for prediction of the time-drug concentration profiles separately for ocular tissues as well as for particular layers of the corneal patch. The average drug concentration changes were assumed to result from the specific interplay between diffusive-advective drug transport and the drug release from particular layers of the designed corneal patch. The developed in silico model was validated against the experimental data on the topically administrated ciprofloxacin.


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