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The dual inhibitor of the 5-lipoxygenase-activating protein (FLAP) and the microsomal prostaglandin E 2 synthase-1 (mPGES-1), named BRP-187, represents a promising drug candidate due to its improved anti-inflammatory efficacy along with potentially reduced side effects in comparison to non-steroidal anti-inflammatory drugs (NSAIDs). However, BRP-187 is an acidic lipophilic drug and reveals only poor water solubility along with a strong tendency for plasma protein binding. Therefore, encapsulation in polymeric nanoparticles is a promising approach to enable its therapeutic use. With the aim to optimize the encapsulation of BRP-187 into poly(lactic- co -glycolic acid) (PLGA) nanoparticles, a single-phase herringbone microfluidic mixer was used for the particle preparation. Various formulation parameters, such as total flow rates, flow rate ratio, the concentration of the poly(vinyl alcohol) (PVA) as a surfactant, initial polymer concentration, as well as presence of a co-solvent on the final particle size distribution and drug loading, were screened for best particle characteristics and highest drug loading capacities. While the size of the particles remained in the targeted region between 121 and 259 nm with low polydispersities (0.05 to 0.2), large differences were found in the BRP-187 loading capacities (LC = 0.5 to 7.29%) and drug crystal formation during the various formulations.

Optimized Encapsulation of the FLAP/PGES-1 Inhibitor BRP-187 in PVA-Stabilized PLGA Nanoparticles Using Microfluidics