Phase-Transition Microneedle Patches for Efficient and Accurate Transdermal Delivery of Insulin

Utilizing the unique virtue of polyvinyl alcohol (PVA) of forming microcrystalline domains as the cross-linking junctions, a new microneedle system, phase-transition microneedle (PTM) patch, is invented, which enables highly efficient transdermal delivery of insulin without depositing the needle tip materials to the skin. PTM, formed of biocompatible PVA as the main component, is sufficiently strong for its needle tip to penetrate the epidermis in the dry state, release preloaded cargos by absorbing body fluid in the dermis layer nearly as fast as subcutaneous injection, and retain mechanical toughness in the hydrated state to ensure complete removal from the skin. The microcrystalline cross-linking enables a protein-friendly fabrication process free of hazardous cross-linking agents required for chemical and ionic cross-linking. Pharmacokinetic and efficacy studies of insulin-loaded PTM using pig models indicate a transdermal bioavailability over 20%, similar deviations and peak width, only 18 min behind Tmax, and lower glycated hemoglobin (HbA_1c) as compared with injection pens. The complete removability of hydrated needle tips may endow PTM with an additional safety insurance, terminating medication whenever hypoglycemia becomes a concern. PTM patch is practically applicable to a variety of protein/peptide medicines requiring frequent dosing by offering painless administration, freedom of refrigeration, and minimal safety concerns.