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单剂长效微阵列贴剂,具有超高载药量和多次释放热稳定抗体的功能。

Single-Administration Long-Acting Microarray Patch with Ultrahigh Loading Capacity and Multiple Releases of Thermally Stable Antibodies.

机构信息

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.

出版信息

Mol Pharm. 2023 May 1;20(5):2352-2361. doi: 10.1021/acs.molpharmaceut.2c00919. Epub 2023 Apr 4.


DOI:10.1021/acs.molpharmaceut.2c00919
PMID:37014806
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10155177/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392c/10155177/35ac7ded97cd/mp2c00919_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392c/10155177/225ef03c9abc/mp2c00919_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392c/10155177/1323ab1c01dc/mp2c00919_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392c/10155177/41c6a4a1d5c8/mp2c00919_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392c/10155177/35ac7ded97cd/mp2c00919_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392c/10155177/225ef03c9abc/mp2c00919_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392c/10155177/1323ab1c01dc/mp2c00919_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392c/10155177/41c6a4a1d5c8/mp2c00919_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/392c/10155177/35ac7ded97cd/mp2c00919_0005.jpg

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[5]
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本文引用的文献

[1]
A Single-Administration Microneedle Skin Patch for Multi-Burst Release of Vaccine against SARS-CoV-2.

Adv Mater Technol. 2022-10-30

[2]
Experimental and computational understanding of pulsatile release mechanism from biodegradable core-shell microparticles.

Sci Adv. 2022-7-15

[3]
Efficient Drug Delivery into Skin Using a Biphasic Dissolvable Microneedle Patch with Water-Insoluble Backing.

Adv Funct Mater. 2021-10-26

[4]
Strategies for eliciting multiple lineages of broadly neutralizing antibodies to HIV by vaccination.

Curr Opin Virol. 2021-12

[5]
Microneedle patch designs to increase dose administered to human subjects.

J Control Release. 2021-11-10

[6]
Fabrication of pure-drug microneedles for delivery of montelukast sodium.

Drug Deliv Transl Res. 2022-2

[7]
FDA approves 100th monoclonal antibody product.

Nat Rev Drug Discov. 2021-7

[8]
Dissolvable Microneedle Patches to Enable Increased Access to Vaccines against SARS-CoV-2 and Future Pandemic Outbreaks.

Vaccines (Basel). 2021-4-1

[9]
Microneedle for transdermal drug delivery: current trends and fabrication.

J Pharm Investig. 2021

[10]
Multifunctional Role of Polyvinylpyrrolidone in Pharmaceutical Formulations.

AAPS PharmSciTech. 2021-1-6

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