Rapid Transdermal Delivery of Insulin to Diabetic Rats Using Poly-γ-glutamic acid (γ-PGA) Microneedles

Abstract

This study presents a dissolving microneedle system which is composed of poly-?-glutamic acid (?-PGA) microneedles with a poly(vinyl pyrrolidone)/poly(vinyl alcohol) supporting array for rapid and efficient transdermal delivery of insulin The microneedles can be completely dissolved after insertion into the skin for 4 min (and the encapsulated insulin is released rapidly) A histological examination shows that the mechanical strength of microneedles is strong to pierce into porcine cadaver skin to a depth of approximately 400 ?m and about 500 ?m in rat skin depth Insulin-loaded microneedles were administered to diabetic rats using a homemade applicator to evaluate the feasibility of using these microneedles for diabetes treatment Pharmacodynamic and pharmacokinetic results show a similar hypoglycemic effect in rats receiving insulin-loaded microneedles and subcutaneous injection of insulin The relative pharmacological availability and relative bioavailability of insulin were both 98-99% compared to subcutaneous injection for the two administration indicating that insulin delivered via γ-PGA microneedles was almost completely absorbed from the skin into systemic circulation The hypoglycemic effect of insulin-loaded microneedles was almost similar to that of the subcutaneous administration of insulin of the same dose Storage ability analysis confirms that more than 90% of the insulin remained in the microneedles even after storage at room temperature (25 ?C) and 37 ?C for 1 month These results demonstrate that the proposed γ-PGA microneedles are stable for encapsulating bioactive molecules and have great potential for transdermal delivery of protein drugs in a relatively painless rapid and convenient manner

Date of Award	2014 Aug 27
Original language	English
Supervisor	Mei-Chin Chen (Supervisor)