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Anita Nikolova Penkova, Amin Naghdloo, Mark Humayun, Satwindar Singh Sadhal; Sustained-Release Drug Implants in the Vitreous Humor: Analytical and Computational Modeling. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2203.
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For patients requiring regular ocular drug therapy, frequent intravitreal injection is painful, undesirable, and unnecessarily risky, and therefore, sustained delivery is a viable alternative. One type of sustained-release systems includes micro-pellets loaded with the drug, encapsulated in a porous shell that can be injected into the vitreous humor where the released drug diffuses while the physiological flow of water provides the convective transport. The purpose of this work is to quantify the drug release rate from a spherical microcapsule for given drug diffusion and capsule permeability properties in the vitreous. The goal is to provide useful parameters such as capsule half-life for various transport parameters for the system.
The model consists of a porous microsphere shell encapsulating a specific drug. The fluid flow within the vitreous is described by Darcy’s equations for the analytical model and Brinkman flow for the computational analysis, while the drug transport is given by the classical convection-diffusion equation. With the timescale for the drug depletion being quite large, we consider the exterior surrounding the capsule to be quasi-steady and the interior is time dependent. In the vitreous, the fluid-flow process is relatively slow, and meaningful results can be obtained for small Peclet number (Pe) whereby a perturbation analysis is possible. For an isolated capsule, with approximately uniform flow in the far-field around it, the mass-transfer problem requires singular perturbation with inner and outer matching. The computational model, however, allows for fully time-dependent solution and also admits large Peclet numbers.
The analytical/computational modeling provides the drug distribution within and around the microsphere. Additionally, the effective lifetime of the drug capsule is obtained in terms of the shell permeability and the biophysical transport parameters. The perturbation analysis has been carried out to order Pe2 and agrees very well with the computational model. The results are sufficiently general and may be applied to a range of drugs and capsule permeability.
The release rate diminishes with time as expected since the drug source depletes and lowers the driving potential. The predictive results are applicable to the design of the sustained-release microspheres, especially in terms of selecting the capsule permeability.
This is a 2021 ARVO Annual Meeting abstract.
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