Modeling and Design of Chitosan-PCL Bi-Layered Microspheres for Intravitreal Controlled Release

Chronic retinal diseases usually require repetitive local dosing. Depending on factors such as dosing frequency, mode of administration, and associated costs, this can result in poor patient compliance. A better alternative involves using controlled release drug delivery systems to reduce the frequency of intravitreal dosing and extend drug release. However, reaching the market stage is a time-consuming process. In this study, we employed two computational approaches to model and estimate the parameters governing the diffusion-controlled drug release of bovine serum albumin and bevacizumab (an agent that slows neovascularization due to retinal disorders) from bi-layered core-shell microspheres composed of chitosan and polycaprolactone (PCL). We used the estimated parameters to simulate the cumulative release under various conditions, optimize device design to guide future experimental efforts and improve the duration of release above a target daily therapeutic release rate from the microspheres. We investigated the effects of polymeric layer sizes on drug release. We provided straightforward computational tools for others to reuse in designing bi-layered microspheres suitable for addressing intravitreal drug delivery needs in the treatment of ocular neovascularization in chronic retinal diseases.