Department of Biomedical Engineering, University of Connecticut, 181 Auditorium Road, Storrs, Connecticut 06269, United States.
Department of Mechanical Engineering, University of Connecticut, 191 Auditorium Road, Storrs, Connecticut 06269 United States.
Mol Pharm. 2023 May 1;20(5):2352-2361. doi: 10.1021/acs.molpharmaceut.2c00919. Epub 2023 Apr 4.
Current antibody (Ab) therapies require development of stable formulations and an optimal delivery system. Here, we present a new strategy to create a single-administration long-lasting Ab-delivery microarray (MA) patch, which can carry high doses of thermally stabilized Abs. The MA fabricated by an additive three-dimensional manufacturing technology can be fully embedded into the skin via a single application to deliver doses of Abs at multiple programmable time points, thus sustaining Ab concentrations in systemic circulation. We developed an MA formulation that stabilized and delivered human immunoglobulins (hIg) in a time-controlled manner while maintaining their structure and functionality. As an example, the b12 Ab─a broadly neutralizing Ab against HIV-1─maintained antiviral activity in vitro after MA manufacturing and heat exposure. Pharmacokinetic studies of MA patch-delivered hIg in rats successfully provided a proof of concept for concurrent and time-delayed Ab delivery. These MA patches codeliver different Abs, providing a tool for expanded protection against viral infections or combination HIV therapy and prevention.
目前的抗体(Ab)治疗需要开发稳定的制剂和最佳的给药系统。在这里,我们提出了一种新的策略,来创建一种单次给药的长效 Ab 递药微阵列(MA)贴剂,它可以携带高剂量的热稳定 Ab。通过增材三维制造技术制造的 MA 可以通过单次应用完全嵌入皮肤,以在多个可编程时间点递送电剂量的 Ab,从而维持 Ab 在全身循环中的浓度。我们开发了一种 MA 配方,该配方以时间控制的方式稳定和递送人免疫球蛋白(hIg),同时保持其结构和功能。例如,b12 Ab——一种广泛中和 HIV-1 的中和抗体——在 MA 制造和热暴露后仍保持体外抗病毒活性。MA 贴剂递送电 hIg 的药代动力学研究在大鼠中成功地为同时和延迟 Ab 递药提供了概念验证。这些 MA 贴片共递送不同的 Abs,为针对病毒感染或联合 HIV 治疗和预防的扩展保护提供了一种工具。
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