Towards scale-up and regulatory shelf-stability testing of curcumin encapsulated polyester nanoparticles.

This study reports scale-up and shelf-stability of curcumin encapsulated poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles. The curcumin encapsulated PLGA nanoparticles were prepared by emulsification solvent evaporation/diffusion, and large quantities were made by varying the homogenisation time (5, 15 and 30 min). The particle size decreased as the homogenisation duration increased from 5 to 30 min, and the particles were spherical as confirmed by atomic force microscopy. For the large-scale preparations, the mean particles size was found to be 288.7 ± 3.4 (polydispersity index 0.15 ± 0.01) with curcumin entrapment 52.5 ± 4.3 %, which were comparable to the lab-scale preparations. The curcumin encapsulated nanoparticles were freeze-dried using sucrose (5 %, w/v) as a cryoprotectant. The freeze-dried nanoparticles were subjected to 6-month stability study as per the International Conference on Harmonisation guideline at room temperature and refrigerated storage conditions. Intermediate sampling was done (monthly), and the nanoparticles were thoroughly characterised for particle size, entrapment efficiency, surface morphology and crystallinity, which were compared to fresh preparations. The curcumin encapsulated PLGA nanoparticles were found to be stable at refrigerated as well as room temperature storage test conditions indicated by their particle characteristics. X-ray diffraction results confirm amorphous nature of curcumin on nano-encapsulation that stays intact after freeze drying and 6-month stability testing. Together these data offer possibility of producing large quantities of polymer nanoparticles that are suitable for room as well as refrigerated storage conditions opening up possibilities to conduct repeated dosings in a chronic setting or regulatory toxicology studies of such nanomedicines.