Pilot-Scale Optimization Of The Solvent Exchange Production And Lyophilization Processing Of Peg-Pla Block Copolymer-Encapsulated Cawo4 Radioluminescent Nanoparticles For Theranostic Applications

Previous studies have shown that calcium tungstate (CaWO4) nanoparticles (NPs) can be used as a radiosensitizing/X-ray contrast agent for cancer treatment. However, due to the propensity of calcium tungstate to agglomerate in physiological solutions, there is a need to encapsulate these NPs within poly(ethylene glycol)-poly(D,L-lactic acid) (PEG-PLA) polymeric micelles through a solvent exchange process. Several parameters including solvent type, polymer to NP ratio, mixing method, and lyophilization were studied to optimize the encapsulation and storage procedures for future scale-up. Herein, we report that the cosolvent that was previously used in this procedure (dimethylformamide) can be replaced with a less toxic cosolvent (acetone), the polymer to NP ratio can be reduced from 600:1 to 50:1 without increasing the particle size by 20%, and mixing methods that create a more uniform flow field produce a more homogenous and less polydisperse particle distribution. In addition, our results indicate that sucrose as a lyophilization excipient produces less agglomeration during freeze-drying compared to mannitol. The smaller molecular weight 2 kDa and 2 kDa ("2 k-2 k") PEG-PLA was less prone to agglomeration during freeze-drying compared to 5 k-5 k PEG-PLA.