Enhanced delivery efficiency and sustained release of biopharmaceuticals by complexation-based gel encapsulated coated microneedles: rhIFNα-1b example

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 rhIFN alpha-1b GEC-MNs was confirmed to achieve biosafety and 6-month storage stability. Pharmacokinetics of rhIFN alpha-1b in GEC-MNs showed a linearly dose dependent relationship. The AUC of rhIFN alpha-1b in GEC-MNs (4.51 ng/mlmiddoth) was bioequivalent to the intradermal (ID) injection (5.36 ng/mlmiddoth) and significantly higher than water-soluble coated MNs (3.12 ng/mlmiddoth). The rhIFN alpha-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 watersoluble drug in coating MNs, constituting a high value to biopharmaceutical. (C) 2021 Shenyang Pharmaceutical University. Published by Elsevier B.V.

Automated summary

A novel gel encapsulated coated microneedle (GEC-MN) has been developed with improved drug delivery efficiency and sustained-release effect compared to traditional water-soluble coated MNs. The biosafety and stability of GEC-MNs have been confirmed, showing a linearly dose dependent relationship in pharmacokinetics.