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

被引:10
作者
Tran, Khanh T. M. [1 ]
Le, Thinh T. [1 ]
Agrahari, Vivek [3 ]
Ouattara, Louise A. [3 ]
Anderson, Sharon M. [3 ]
Le-Kim, Trang Huyen [2 ,4 ]
Singh, Onkar N. [3 ,5 ]
Doncel, Gustavo F. [3 ]
Nguyen, Thanh D. [1 ,2 ]
Peet, M. Melissa [3 ]
机构
[1] Univ Connecticut, Dept Biomed Engn, Storrs, CT 06269 USA
[2] Univ Connecticut, Dept Mech Engn, Storrs, CT 06269 USA
[3] Eastern Virginia Med Sch, CONRAD, Norfolk, VA 23507 USA
[4] Korea Adv Inst Sci & Technol, Dept Mat Sci & Engn, Daejeon, South Korea
[5] Alentia Therapeut, CMC Mfg & Tech Operat, Summit, NJ USA
关键词
microarray patch; fabrications; therapeutic antibodies; protein stabilization; long-acting delivery; DISSOLVING MICRONEEDLES; SUSTAINED-RELEASE; DRUG; IGG; DELIVERY; FABRICATION; TREHALOSE; COMPLEX;
D O I
10.1021/acs.molpharmaceut.2c00919
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:2352 / 2361
页数:10
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