Enhancing the Transdermal Delivery of 'Next Generation' Variable New Antigen Receptors Using Microarray Patch Technology: a Proof-of-Concept Study.
Enhancing the Transdermal Delivery of 'Next Generation' Variable New Antigen Receptors Using Microarray Patch Technology: a Proof-of-Concept Study.
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使用微阵列贴片技术增强“下一代”可变新抗原受体的透皮递送：概念验证研究。
DOI：
10.1016/j.xphs.2022.08.027
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发表时间：
2022
影响因子：
3.8
通讯作者：
Hutton ARJ
中科院分区：
文献类型：
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作者：
Hutton ARJ
仅重链结合蛋白，例如可变新抗原受体 (VNAR)，已成为非常成功的治疗性单克隆抗体 (mAb) 的替代品。由于它们的尺寸小（~ 11 kDa）和单链结构，它们适合模块化重新格式化，并且可以使用廉价的表达系统进行生产。此外，由于它们的低分子量（MW）和高稳定性，它们可能适合替代递送策略，例如微阵列贴片（MAP）。在这项研究中，使用溶解性和水凝胶形成的 MAP 来检查 ELN22-104（一种多价抗 hTNF-α VNAR）的透皮递送。对于溶解的 MAP，ELN22-104 的累积体外渗透在 2 小时后达到稳定水平 (12.24 ± 0.17 µg)。这对于推注剂量可能很重要。在体外评估两种水凝胶形成的 MAP，与“超溶胀”MAP 相比，PVP/PVA 水凝胶形成的 MAP 递送的药物剂量显着更高，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，通过修改 MAP 系统，可以增强 VNAR 穿过皮肤的透皮递送。此外，这项概念验证研究表明，使用 MAP 技术可以实现“下一代”生物治疗药物的透皮给药。
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 cumulativein vitropermeation 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 MAPsin 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.