Production of dasatinib encapsulated spray-dried poly (lactic-co-glycolic acid) particles

Abstract Fibrotic scarring of the retina, termed proliferative vitreoretinopathy (PVR), can cause permanent visual impairment and blindness following corrective surgery for retinal detachment and/or ocular trauma. We have previously shown that multiple intravitreal injections of dasatinib prevent PVR in an animal model. The aim of this research was to develop injectable sustained release systems for dasatinib, which would be preferred for clinical use over multiple ocular injections. To accomplish this, dasatinib was encapsulated in Poly (lactic-co-glycolic acid) [PLGA] particles via a benchtop spray-drying process. Spray drying parameters were optimized using a taguchi statistical approach to obtain particle size between 0.5 and 1.5  μm. Characterization of two different sets of particles, sub-micron and >1.0  μm in average diameter, respectively, showed that dasatinib release from sub-micron particles lasts 15 days while release from particles with diameters >1.0  μm lasts up to 55 days. Zeta potential measurement of aqueous buffer suspended particles suggests sub-micron particles to be more stable in aqueous environment compared to >1.0  μm particles. Dasatinib released from these particles maintained therapeutic efficacy, as dasatinib incorporated PLGA particles significantly inhibited the contraction of collagen matrices compared to PLGA (control) particles when tested on an in vitro scar contraction assay.