SSPC, the SFI Research Centre for Pharmaceuticals, School of Pharmacy, University College Cork, Cork T12 YT20, Ireland.
SSPC, the SFI Research Centre for Pharmaceuticals, School of Pharmacy, University College Cork, Cork T12 YT20, Ireland.
Eur J Pharm Biopharm. 2024 Nov;204:114517. doi: 10.1016/j.ejpb.2024.114517. Epub 2024 Sep 28.
Protein therapeutics are essential in the treatment of various diseases, but most of them require parenteral administration. Since intravenous and subcutaneous injections are associated with discomfort and pain, other routes have been investigated including intradermal microneedle delivery. Microneedles are shorter than hypodermic needles and therefore minimize contact with pain receptors in deeper skin layers. But the differences in anatomical and physiological characteristics of dermis and subcutis can potentially result in varying protein penetration through the skin, absorption, and metabolism. This review summarizes pharmacokinetic studies that compare the administration of protein therapeutics by subcutaneous injections and different types of microneedles intradermally including hollow, dissolvable, coated, and hydrogel-forming microneedles. Across animal and human studies, hollow microneedle delivery resulted in quicker and higher peak plasma levels of proteins and comparable bioavailability to subcutaneous injections potentially due to the extensive network of lymphatic and blood vessels in the dermis. In case of dissolvable and coated microneedles, drug release kinetics depend on component materials. The dissolution of polymer excipients can slow the release and permeation of protein therapeutics at the administration site and thereby delay absorption. The understanding of drug penetration through different skin layers, its absorption into blood capillaries or lymphatics, and dermal metabolism remains limited. Additionally, the effects of these processes on the differences in pharmacokinetic profiles of proteins following intradermal microneedle administration are not well understood. Greater insights are required for the development of the next generation of intradermal microneedle biotherapeutics.
蛋白质疗法在治疗各种疾病中至关重要，但大多数都需要通过注射给药。由于静脉和皮下注射会引起不适和疼痛，因此人们研究了其他途径，包括皮内微针给药。微针比皮下注射针短，因此最大限度地减少了与深层皮肤层中疼痛感受器的接触。但是，真皮和皮下组织的解剖和生理特性的差异可能导致蛋白质通过皮肤的渗透、吸收和代谢存在差异。这篇综述总结了比较蛋白质治疗剂通过皮下注射和不同类型的皮内微针（包括空心、可溶解、涂层和水凝胶形成微针）给药的药代动力学研究。在动物和人体研究中，空心微针给药导致蛋白质更快达到更高的峰值血浆水平，生物利用度与皮下注射相当，这可能是由于真皮中广泛的淋巴管和血管网络所致。对于可溶解和涂层的微针，药物释放动力学取决于成分材料。聚合物赋形剂的溶解会减缓药物在给药部位的释放和渗透，从而延迟吸收。药物通过不同皮肤层的渗透、进入毛细血管或淋巴管的吸收以及真皮代谢的理解仍然有限。此外，这些过程对皮内微针给药后蛋白质药代动力学特征差异的影响尚不清楚。需要更多的见解来开发下一代皮内微针生物疗法。
