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 α-1b GEC-MNs was confirmed to achieve biosafety and 6- month storage stability. Pharmacokinetics of rhIFN α-1b in GEC-MNs showed a linearly dosedependent relationship. The AUC of rhIFN α-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 rhIFN α-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 GECMNs have proved to be more efficient, stable, and achieve the sustained-release of watersoluble drug in coating MNs, constituting a high value to biopharmaceutical. [ABSTRACT FROM AUTHOR]