Fumaryl Diketopiperazine Microspheres Platform Design for Protein Pulmonary Delivery in Diabetes Rats Model.

Abstract

The cornerstone of this study was to formulate and optimize fumaryl diketopiperazine (FDKP) microspheres of insulin-load (INS@FDKP-MPs) with the aid of Box-Behnken design (BBD) to enhance insulin bioavailability. The property characterization of INS@FDKP-MPs was studied and the stability study was confirmed by evaluating the effect on sample appearance, insulin and related protein content, hygroscopicity. At the same time, the pharmacodynamics of INS@FDKP-MPs was evaluated by testing the concentration of blood glucose of the diabetic model rats under different conditions. The optimized formulation of INS@FDKP-MPs drug loading microspheres is 2.37 h of stirring time, 4.64 of pH value and 23.11% of the drug ratio. Under this condition, the results of optimized formulation showed the average microspheres size of 1.69 nm, the drug loading rate of 10.95%. The size of microspheres is all below 3 m and the pulmonary deposition rate in stage 3 and stage 4 is more than twice that of other stages. The results of stability confirmed that INS@FDKP-MPs had good stability within three months. Futhermore, pharmacodynamics results indicated that inhaled insulin (Tmin 60 to 90 min) could rapidly be absorbed into the systemic circulation compared to subcutaneous injection (Tmin 120 min); Inhaled insulin can continuously reduce blood glucose concentration within 120 minutes, which is significantly faster than subcutaneous injection (180 minutes). That is stand for reducing the possibility of hypoglycemia. Through Pulmonary Administration, INS@FDKP-MPs can be efficiently and effectively absorbed into the systemic circulation with good pharmacodynamics and the ability to lower blood glucose levels.