Production of high loading insulin nanoparticles suitable for oral delivery by spray drying and freeze drying techniques
Insulin nanoparticles (NPs) with high loading content have found diverse applications in different dosage forms. This work aimed to evaluate the impact of freeze-drying and spray drying process on the structures of insulin-loaded chitosan nanoparticles, with or without mannitol as cryoprotectants. We also assessed the quality of these nanoparticles by redissolving them. Before dehydration, the chitosan/sodium tripolyphosphate/insulin crosslinked nanoparticles were optimized to 318 nm of particle size, 0.18 of PDI, 99.4% of entrapment efficiency, and 25.01% of loading content. After reconstitution, all nanoparticles, except the one produced by the freeze-drying method without using mannitol, maintained their spherical particle structure. The nanoparticles dehydrated by spray drying without mannitol also showed the smallest mean particle size (376 nm) and highest loading content (25.02%) with similar entrapment efficiency (98.7%) and PDI (0.20) compared to mannitol-containing nanoparticles dehydrated by either spray drying or freeze-drying techniques. The nanoparticles dried by spray drying without mannitol also resulted in the fastest release and highest cellular uptake efficacy of insulin. This work shows that spray drying can dehydrate insulin nanoparticles without the need for cryoprotectants, creating a significant advantage in terms of greater loading capacity with lower additive requirements and operating costs as compared to conventional freeze drying approaches.
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Article by: Guo, Y., Baldelli, A., Singh, A. et al. Production of high loading insulin nanoparticles suitable for oral delivery by spray drying and freeze drying techniques. Sci Rep 12, 9949 (2022). https://doi.org/10.1038/s41598-022-13092-6
Materials
Chitosan (Average Mw 100 KDa, 75–85% deacetylated) was purchased from Sigma-Aldrich. (Oakville, Ontario, Canada). Sodium tripolyphosphate (TPP) was purchased from VWR (Radnor, Pennsylvania, USA). Recombinant human insulin used in this study was from Fisher Scientific (Waltham, Massachusetts, USA). Fluorescein isothiocyanate (FITC)-labelled human insulin and the 4’, 6-Diamidino-2-phenylindole dihydrochloride (DAPI) were purchased from Sigma-Aldrich. (Oakville, Ontario, Canada). The HepG2 cell line was obtained from ATCC (Manassas, Virginia, USA). All the other reagents were of analytical or chromatography grade.