UNASSIGNED: The purpose of this work was to evaluate the influence of the co-encapsulation of lyoprotectants with @entity2690 into @entity7050 nanoparticles, on the stability of the protein and nanoparticles upon lyophilization. Different lyoprotectants were used, namely @entity7970 , @entity413 , @entity969 , @entity948 and @entity5121 at 10% (w/v). @entity2690 -loaded @entity7050 nanoparticles with co-encapsulated lyoprotectants achieved a mean particle size of 386-466nm, and a zeta potential ranging between -34 and -38mV, dependent on the lyoprotectant used. Formulations had association efficiencies and loading capacities of 85-91% and 10-12%, respectively. The lyophilization process increased the colloidal stability of nanoparticles, and maintained their spherical shape and smooth surface, particularly in presence of lyoprotectants. XRPD revealed that the lyophilizates of nanoparticles with co-encapsulated lyoprotectants were amorphous, whereas formulations with externally added lyoprotectants, except @entity7970 , showed crystallinity. FTIR assessment showed that co-encapsulating lyoprotectants better preserved @entity2690 structure upon lyophilization with a spectral area overlap of 82-87%, compared to only 72% in lyoprotectant absence. These results were confirmed by circular dichroism spectroscopy. Surprisingly, the simultaneous co-encapsulation and addition of lyoprotectants was detrimental to protein stabilization. The @entity2690 in vitro release studies demonstrated that formulations with co-encapsulated @entity7970 , @entity413 , @entity969 , @entity948 and @entity5121 achieved 83%, 69%, 70%, 77% and 74%, respectively after 48h. In contrast, formulations added with those lyoprotectants prior lyophilization showed a lower release rate not higher than 60% after 48h. This work gives rise to a different promising strategy of co-encapsulating lyoprotectants and therapeutic proteins, to better stabilize protein structure upon lyophilization.

Co-encapsulation of lyoprotectants improves the stability of protein-loaded XXXX nanoparticles upon lyophilization.

@entity7970 :: ('MESH:D014199', 'Chemical') :: ['trehalose'] @entity948 :: ('MESH:D005632', 'Chemical') :: ['fructose'] @entity5121 :: ('MESH:D013012', 'Chemical') :: ['sorbitol'] @entity2690 :: ('3630', 'Gene') :: ['Insulin', 'insulin'] @entity7050 :: ('MESH:C043435', 'Chemical') :: ['PLGA'] @entity969 :: ('MESH:D013395', 'Chemical') :: ['sucrose'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity7050 :: (MESH:C043435,Chemical) :: ['PLGA']
