School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, United Kingdom.
Elasmogen Ltd., Liberty Building, Foresterhill Road, Aberdeen AB25 2ZP, United Kingdom.
J Pharm Sci. 2022 Dec;111(12):3362-3376. doi: 10.1016/j.xphs.2022.08.027. Epub 2022 Aug 26.
Heavy chain only binding proteins, such as variable new antigen receptors (VNARs), have emerged as an alternative to the highly successful therapeutic monoclonal antibodies (mAb). Owing to their small size (∼ 11 kDa) and single chain only architecture, they are amenable to modular reformatting and can be produced using inexpensive expression systems. Furthermore, due to their low molecular weight (MW) and high stability, they may be suitable for alternative delivery strategies, such as microarray array patches (MAPs). In this study, the transdermal delivery of ELN22-104, a multivalent anti-hTNF-α VNAR, was examined using both dissolving and hydrogel-forming MAPs. For dissolving MAPs, the cumulative in vitro permeation of ELN22-104 reached a plateau after 2 h (12.24 ± 0.17 µg). This could be important for bolus dosing. Assessing two hydrogel-forming MAPs in vitro, PVP/PVA hydrogel-forming MAPs delivered significantly higher drug doses when compared to 'super swelling' MAPs, equivalent to 43.13 ± 10.36 µg and 23.13 ± 5.66 µg, respectively (p < 0.05). Consequently, this study has proven that by modifying the MAP system, the transdermal delivery of a VNAR across the skin can be enhanced. Furthermore, this proof-of-concept study has shown that transdermal delivery of 'next generation' biotherapeutics is achievable using MAP technology.
重链仅结合蛋白，如可变新抗原受体（VNAR），已经成为高度成功的治疗性单克隆抗体（mAb）的替代品。由于其体积小（约 11 kDa）和单链结构，它们易于进行模块化改造，可以使用廉价的表达系统进行生产。此外，由于其低分子量（MW）和高稳定性，它们可能适合替代的给药策略，如微阵列贴片（MAPs）。在这项研究中，使用溶解型和水凝胶形成型 MAP 研究了多价抗 hTNF-α VNAR ELN22-104 的经皮传递。对于溶解型 MAP，ELN22-104 的体外累积渗透在 2 小时后达到平台期（12.24 ± 0.17 µg）。这对于推注给药可能很重要。在体外评估两种水凝胶形成型 MAP 时，与“超级膨胀”型 MAP 相比，PVP/PVA 水凝胶形成型 MAP 递送的药物剂量显著更高，分别相当于 43.13 ± 10.36 µg 和 23.13 ± 5.66 µg（p < 0.05）。因此，这项研究证明，通过修饰 MAP 系统，可以增强 VNAR 经皮穿过皮肤的传递。此外，这项概念验证研究表明，使用 MAP 技术可以实现“下一代”生物疗法的经皮传递。
