Facile Photolithographic Fabrication of Zwitterionic Polymer Microneedles with Protein Aggregation Inhibition for Transdermal Drug Delivery.

Microneedle technology has received considerable attention in transdermal drug delivery system research owing to its minimally invasive and convenient self-administration with enhanced transdermal transport. The pre-drug loading microneedle method has been developed for several protein and chemical medicines. However, the protein activity and efficacy are severely affected owing to protein aggregation. Herein, we aim to develop non-degradable hydrogel photocross-linkable microneedles for suppressing protein aggregation. Four-point star-shaped microneedles are fabricated via a photolithography process, and sulfobetaine (SPB) monomer is combined with dextran-glycidyl methacrylate/acrylic acid to form the hydrogel network. Incorporating zwitterionic poly-sulfobetaine (poly-SPB) in the microneedles enables the protection of proteins from denaturation even under external stress, releases the proteins in their native state (without activity loss), and exhibits sufficient mechanical strength to penetrate porcine skin. The microneedles exhibit a high drug loading capacity along with an efficient drug release rate. The rhodamine B drug loading and release model shows that the microneedles can load 8 μg of drugs on one microneedle patch of 41 needles and release nearly 80% of its load within 1 h. We anticipate that this pre-drug loading platform and the advanced features of the microneedles can provide an effective option for administering therapeutic drugs.