Zhou Zequan, Zhang Suohui, Yang Guozhong, Gao Yunhua
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Asian J Pharm Sci. 2021 Sep;16(5):612-622. doi: 10.1016/j.ajps.2021.05.002. Epub 2021 Jun 26.
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) 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 drug release. The sustained-release of BSA was observed 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.
包衣微针（MNs）被广泛用于生物药物递送。在本研究中，开发了一种新型的凝胶包封包衣微针（GEC-MNs）。水溶性药物包衣被藻酸钠（SA）络合凝胶包封。对GEC-MNs的制造工艺进行了优化以实现大规模生产。与水溶性包衣微针（72.02% ± 11.49%）相比，优化后的GEC-MNs的药物递送效率（88.42% ± 6.72%）稳步提高，并通过药物释放对这种提高进行了研究。观察到牛血清白蛋白（BSA）通过皮肤渗透实现了缓释。证实rhIFNα-1b GEC-MNs具有生物安全性和6个月的储存稳定性。rhIFNα-1b在GEC-MNs中的药代动力学显示出线性剂量依赖性关系。GEC-MNs中rhIFNα-1b的曲线下面积（AUC）（4.51 ng/ml·h）与皮内（ID）注射（5.36 ng/ml·h）具有生物等效性，且显著高于水溶性包衣微针（3.12 ng/ml·h）。GEC-MNs、可溶性包衣微针和ID注射的rhIFNα-1b消除半衰期分别为18.16、1.44和2.53小时。基于络合的GEC-MNs已被证明更高效、稳定，并能在包衣微针中实现水溶性药物的缓释，对生物制药具有很高的价值。
