Fabrication of composite microneedles integrated with insulin-loaded CaCO3 microparticles and PVP for transdermal delivery in diabetic rats.

Dissolving microneedles (MNs) display high efficiency, safety and painless in transdermal delivery for poorly permeable drugs. Here, a dissolving composite MNs prepared from insulin-loaded CaCO3 microparticles (INS-CaCO3 MPs) and poly(vinyl pyrrolidone) (PVP) as matrix were fabricated with two-step centrifuging and molding process to immobilize insulin in the MNs. The as-prepared INS-CaCO3/PVP MNs exhibited remarkable mechanical strength and slower solubility properties when compared with pure PVP MNs. In vitro skin insertion capability was determined by staining with FITC-labeled insulin which was revealed after insertion, gradually diffusing from the puncture sites to deeper tissues. In vivo pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded dissolving MNs on diabetic rats for glucose regulation. The relative pharmacological availability (RPA) and relative bioavailability (RBA) of insulin from MNs were 98.2 and 96.6%. Thus, this study suggests that the use of INS-CaCO3/PVP MNs achieved both high efficiency and constant release of insulin in comparison with the traditional subcutaneous injection approach and presented a promising device to delivery insulin for diabetic therapy.