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Coated microneedles (MNs) are widely used for delivering biopharmaceuticals. In this study, a novel gel encapsulated coated MNs (GEC-MNs) was developed. The water-soluble drug coating was encapsulated with sodium alginate (SA) in situ complexation gel. The manufacturing process of GEC-MNs was optimized for mass production. Compared to the water-soluble coated MNs (72.02% ± 11.49%), the drug delivery efficiency of the optimized GEC-MNs (88.42% ± 6.72%) was steadily increased, and this improvement was investigated through in vitro drug release. The sustained-release of BSA was observed in vitro permeation through the skin. The rhIFNα-1b GEC-MNs was confirmed to achieve biosafety and 6-month storage stability. Pharmacokinetics of rhIFNα-1b in GEC-MNs showed a linearly dose-dependent relationship. The AUC of rhIFNα-1b in GEC-MNs (4.51 ng/ml·h) was bioequivalent to the intradermal (ID) injection (5.36 ng/ml·h) and significantly higher than water-soluble coated MNs (3.12 ng/ml·h). The rhIFNα-1b elimination half-life of GEC-MNs, soluble coated MNs, and ID injection was 18.16, 1.44, and 2.53 h, respectively. The complexation-based GEC-MNs have proved to be more efficient, stable, and achieve the sustained-release of water-soluble drug in coating MNs, constituting a high value to biopharmaceutical., Graphical abstract In the coated microneedle produced by the layer-by-layer coating method, the water-soluble drug-containing coating is encapsulated by the complexation-based gel (GEC-MNs). After GEC-MNs are applied to the skin, the release rate of the drug is reduced by the outer layer of the gel. The pharmacokinetic results of rh-IFNα-1b showed that compared with intradermal injection and water-soluble coated microneedles, the sustained release was achieved in GEC-MNs.Image, graphical abstract

Daily administration of multiple injections can cause inconvenience and reduce compliance in diabetic patients; thus, microneedle (MN) administration is favored due to its various advantages. Accordingly, the two-layer sustained-release MNs (TS-MNs) were fabricated by encapsulating exenatide (EXT) in calcium alginate (CA) gel in this work. The TS-MNs were composed of a sodium alginate (SA) tip and a water-soluble matrix-containing calcium chloride (CaCl2). Subsequently, the calcium ion (Ca2+) contained in the matrix layer penetrated the tip layer for cross-linking, leaving the drug in the cross-linked network. The patches have adequate mechanical strength to pierce the skin; then, the matrix layer is dissolved, leaving the tip layer to achieve sustained release. Additionally, the TS-MNs encapsulating EXT retained high activity during long-term storage at room temperature. The pharmacokinetic results indicated that the plasma concentrations of EXT were sustained for 48 h in the EXT MN group, which agreed with the in vitro release test. Furthermore, they had high relative bioavailability (83.04%). Moreover, the hypoglycemic effect was observed to last for approximately 24 h after a single administration and remained effective after multiple administrations without drug resistance. These results suggest that the TS-MNs are a promising depot for the sustained delivery of encapsulated EXT.

The aim of this study was to prepare dissolving microneedles (DMNs) patches containing tranexamic acid (TA) for the treatment of melasma. Polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) were preferred as matrix materials through the compatibility experiment. In the in vitro permeation study, the transdermal amount of TA was significantly promoted through dissolving microneedles with the cumulative release was 44.43 ± 6.55%. By comparison, the release of TA solution assisted with solid microneedles (SMNs) was merely 11.31 ± 2.30% (p 0.05). Pharmacokinetics study indicated the bioavailability of dissolving microneedles was more than 1.3 times compared with oral administration. In pharmacodynamics investigation, TA dissolving microneedles obviously reduced melanin deposition in the skin of melasma guinea pigs after 8 consecutive administrations. In particular, the combination of tranexamic acid and licorice extract (LIC) dissolving microneedles worked better than tranexamic acid alone. Accelerated stress conditions including high temperature, high humidity, as well as photostability were designed to prove that TA microneedles maintained good pharmaceutical stability. In conclusion, tranexamic acid dissolving microneedles showed reliable quality and remarkable effect. Moreover, the combination of tranexamic acid and licorice extract had a synergistic therapy in melasma.