Optimization of PLGA and PLGA-dasatinib particles through a Taguchi design approach

Proliferative vitreoretinopathy (PVR) is a disease of the retina in the human eye. Retinal pigment epithelium cells (RPE) undergo an epithelial to mesenchymal transition in response to retinal trauma. This transition gives the cells mobility and allows them to potentially infiltrate the vitreous chamber and deposit on either side of the retina. Once cell deposition has occurred, along with several other transformed cells derived from cell types such as Müller glia, these migratory cells can form a membrane contiguous with the retinal extracellular matrix and, upon contraction, cause wrinkling of the retina. If left untreated PVR can lead to traction retinal detachment and blindness. There are limitations to the methods currently being used to treat this disease. The most common treatment option for PVR is surgery, which has a limited success rate. Pharmacological agents, such as the protein kinase inhibitor dasatinib, are also being investigated for their efficacy in treating this condition. Dasatinib has been shown to prevent PVR and associated cellular functions in porcine animal models in a dosedependent manner. One of the limitations of using dasatinib, however, is the need for recurring drug injections to keep a therapeutic level in the eye and prevent retinal contracture. Targeted ocular drug delivery, through the use of polymeric nanoparticles, offers a promising method to deliver dasatinib to the eye without the need for frequent daily injections. In this project, spray drying, a technique that produces drug-encapsulated polymer shells from a liquid dispersion, was used to encapsulate dasatinib in PLGA v particles. Particle size was optimized to produce particles under 1 μm in diameter through the use of a Taguchi statistical design approach. Particles were manufactured on a Büchi B-90 nanospray spray dryer. PLGA particle optimization was completed before the production of PLGA dasatinib particles. After PLGA particle optimization, PLGA dasatinib particles were produced (n = 3) and their size analyzed using scanning electron microscopy. The release kinetics of dasatinib from the PLGA particles was analyzed using UV-Visible spectroscopy from this the drug release kinetics and mechanism was determined