Fabrication of Tip-Hollow and Tip-Dissolvable Microneedle Arrays for Transdermal Drug Delivery.

We developed a modified micromolding method for the mass production of a novel tip-hollow microneedle array (MA). The tip-hollow MA was fabricated by tuning of the vacuum degree at -80 kPa for 60 s during the micromolding process. Subsequently, a tip-dissolvable MA encapsulated with drugs in the microcraters was fabricated from tip-hollow MA using repeated dipping and the freeze-drying process. Both the tip-hollow and tip-dissolvable MAs could easily penetrate in the rabbit skin without breakage, while the tip-hollow MA can just create a shallow loop hole in the skin. The drug-loaded tip-dissolvable MA can rapidly dissolve, releasing and diffusing the drug in the skin. The tip-dissolvable MA exhibited the best drug permeation ability in that the corresponding flux through the punctured skin using tip-dissolvable MA loaded with Rhodamine B is about 1.7- and 5.8-fold of that through the punctured skin using solid MA and the intact skin, respectively. The tip-dissolvable MA loaded with 5 IU insulin was fabricated to treat the type 1 diabetic SD rats. The tip-dissolvable MA had a good hypoglycemic effect and exhibited longer normoglycemic period in comparison with subcutaneous injection (5 IU). Therefore, our tip-dissolve MA is a promising medical device for transdermal drug delivery.