A novel method for fabrication of coated microneedles with homogeneous and controllable drug dosage for transdermal drug delivery.

Over the years, scientists have been focused on the development of microneedle coating process to coat a broad range of therapeutic agents onto the surface of the solid microneedles for effective drug delivery. The precise dose control, content uniformity as well as large-scale production of coated microneedles are still the core issues that have been the interest of researchers in this topic. To this end, a repeatable method that involved a micro-molding process was demonstrated for mass fabrication of coated microneedles with homogeneous and controllable drug loading under mild conditions. In this system, the dissolvable drug carriers with precise dosage were first mounted onto the solid microneedles and then exposed to the high moisture condition to finally obtain the coated microneedle with uniform and precise drug loading. Using the microneedle molds with the volume of 4.71 nL, 8.24 nL, 10.47 nL, and 12.56 nL per cavity, the drug loadings were precisely controlled at 4.8 ng, 6.4 ng, 9.3 ng, and 13.5 ng per needle, with the standard deviation of 0.09, 0.01, 0.07, and 0.53%, respectively. Mechanical property tests showed that the coated microneedles are strong enough for reliable skin insertion, and with in vivo trials in diabetic mice, we further confirmed the similar hypoglycaemic effect of insulin-coated microneedles to subcutaneous injection. Taken together, the micro-molding-based fabrication process has practical merits in the mass production of coated microneedles with homogeneous and controllable drug loading, facilitating the clinical translation of the microneedle technique.

Assessment of mechanical stability of rapidly separating microneedles for transdermal drug delivery.

The rapidly separating microneedles (RS-PP-MNs), composed of PVA (separable arrow head) MNs and a poly(L-lactide-co-D, L-lactide) (PLA) supporting array, are used for transdermal delivery system at high humidity. The fabricated RS-PP-MNs should have sufficient mechanical strength at different humidity. In general, the water adsorption rate was increased with increasing humidity; by contrast, storage time was decreased with increasing humidity. The higher water adsorption rate indicated the lower mechanical strength, thereby lowering drug delivery efficiency. The prepared RS-PP-MNs could be successfully inserted within the skin at high humid atmosphere due to PLA supporting array. The bright field and fluorescence microscopic images suggested the probable real-time applicability of RS-PP-MNs. The in vitro and in vivo assay suggested that RS-PP-MNs potentially were able to deliver the drugs at high humidity condition. The significant improvement in the drug delivery efficiency and skin penetration ability was observed compared with the traditional MNs. In addition, the fabrication of RS-PP-MNs is facile and scalable. Therefore, the prepared RS-PP-MNs with supporting solid PLA array might be advantageous in real-time applications. This study is of great importance for the MN field as it offers more theoretical support for clinical applications.