Subcutaneous delivery of insulin loaded poly(fumaric-co-sebacic anhydride) microspheres to type 1 diabetic rats.

The method of phase inversion nanoencapsulation (PIN) and microencapsulation was used to produce biodegradable poly(fumaric-co-sebacic anhydride) (p(FASA)) microspheres that contain insulin. Microspheres were characterized by SEM and a laser light scattering technique to determine particle size distribution. Insulin stability was determined by RP and SEC HPLC. Release rate studies were conducted and microspheres were administered subcutaneously (SQ) to type 1 diabetic rats to determine the bioactivity of insulin at three different dosages. Pharmacokinetic parameters for SQ experiments were measured using the trapezoidal rule by plotting average plasma insulin level (PIL) vs. time and determining peak concentration (CP), the time of peak concentration (TP), duration of PIL curve (D), and relative bioavailability (RB). When our insulin containing formulation was analyzed by HPLC, there was no evidence of high molecular weight transformation (HMWT) or deamidated products. In addition, we effectively altered the onset, peak, and duration of insulin action after SQ injection.