LAUSR

To enhance the scope of therapeutic interventions using star polymeric nanoparticles of desired concentrations, an understanding of the effect of converting aqueous formulations into stable redispersible dry powders by freeze drying on their physicochemical and biological properties is essential. We demonstrate that parameters such as the choice of the cryoprotectant, its molecular weight, and concentration play an important role during lyophilization and reconstitution processes. We hypothesized that utilizing cryoprotectants akin to shell-forming polymers may be ideal in protection against aggregation and keeping the nanostructures intact during lyophilization and reconstitution, as well as retaining the overall biological efficacy of their cargo. Through an evaluation of miktoarm polymer-based nanoparticles, we demonstrate that PEG2k at 1% w/v concentration provides the optimized cryoprotection, and the resulting solid formulations upon redispersion in an aqueous medium preserve the desired nanoparticle and curcumin properties. PEG2k at 1% w/v is more efficient than PEG5k and saccharides including glucose, sucrose, trehalose, and mannitol in enhancing the integrity of micelles during lyophilization and reconstitution. Addition of PEG2k 1% w/v (with or without lyophilization and redispersion) enhances drug release in PBS buffer, while it has no impact in the cell culture media. Nanoformulations protect endothelial cells from cytotoxicity of curcumin, and addition of cryoprotectant or the lyophilization/redispersion processes did not impair anti-inflammatory efficacy of curcumin.