Bo Zhi Chen

Fabrication of coated polymer microneedles for transdermal drug delivery

Abstract As an alternative to hypodermic needles, coated polymer microneedles (MNs) are able to deliver drugs to subcutaneous tissues after being inserted into the skin. The dip‐coating process is a versatile, rapid fabricating method that can form coated MNs in a short time. However, it is still a challenge to fabricate coated MNs with homogeneous and precise drug doses in the dip‐coating process. In this study, to fabricate coated polymer microneedles with controlled drug loading, an adjustable apparatus that can be lifted and lowered was designed to immerse a polylactic acid (PLA) MN patch in the coating solutions. Using the coating solution containing 0.5% (w/w) sulforhodamine B, the drug loadings were up to 12 ng, 14 ng, and 18 ng per needle for the MNs with heights of 550 &mgr;m, 650 &mgr;m, and 750 &mgr;m, respectively. Moreover, for the MNs with a 650‐&mgr;m height, when increasing the viscosity of the coating solutions from 150 mPa·s to 1360 mPa·s, 2850 mPa·s, and 8200 mPa·s, the drug loading increased from 2.5 ng to 5 ng, 14 ng, and 22 ng per needle, respectively. Meanwhile, the drug delivery efficiencies of these MNs were approximately 90%. In the insertion experiments, the MNs could successfully penetrate the skin and deliver the coated drug with approximately 90% efficiency when the MN tips were exposed to the outer environment. In vivo studies in mice indicated that the coated polymer MNs continuously delivered drugs, and the skin recovered without any injuries. These results demonstrated that the coated polymer MN was a safe and effective method for transdermal drug delivery. Graphical abstract Figure. No Caption available.

Microneedles with Controlled Bubble Sizes and Drug Distributions for Efficient Transdermal Drug Delivery.

Drug loaded dissolving microneedles (DMNs) fabricated with water soluble polymers have received increasing attentions as a safe and efficient transdermal drug delivery system. Usually, to reach a high drug delivery efficiency, an ideal drug distribution is gathering more drugs in the tip or the top part of DMNs. In this work, we introduce an easy and new method to introduce a bubble with controlled size into the body of DMNs. The introduction of bubbles can prevent the drug diffusion into the whole body of the MNs. The heights of the bubbles are well controlled from 75 μm to 400 μm just by changing the mass concentrations of polymer casting solution from 30 wt% to 10 wt%. The drug-loaded bubble MNs show reliable mechanical properties and successful insertion into the skins. For the MNs prepared from 15 wt% PVA solution, bubble MNs achieve over 80% of drug delivery efficiency in 20 seconds, which is only 10% for the traditional solid MNs. Additionally, the bubble microstructures in the MNs are also demonstrated to be consistent and identical regardless the extension of MN arrays. These scalable bubble MNs may be a promising carrier for the transdermal delivery of various pharmaceuticals.

Controlled Delivery of Insulin Using Rapidly Separating Microneedles Fabricated from Genipin-Crosslinked Gelatin

Rapidly separating genepin-crosslinked gelatin (RS-GC) microneedles (MNs) mounted on the polyvinyl alcohol (PVA)-coated polylactic acid (PLA) MNs (RS-PGC-MNs) are fabricated, in which GC-MNs deliver insulin within the skin and the PLA supporting array is easily separated by the dissolution of the PVA layer. The release of insulin is controlled by utilizing the virtue of genipin as a crosslinking agent for producing biocompatible GC-MNs. The degree of crosslinking enhances the mechanical strength as well as humidity resistance. The in vitro and in vivo insulin release tests show significant changes in the release rates in the RS-PGC-MNs with different crosslinking degree. The hypoglycemic effect in diabetic mice demonstrate that the higher crosslinking GC-MNs result in characteristic controlled insulin release compared with other treatments and prolonged effectiveness of the RS-PGC-MNs. The proposed RS-PGC-MNs is a promising device for effective use as a noninvasive and painless controlled insulin delivery system.

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.