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

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

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.

Keywords: fabrications; long-acting delivery; microarray patch; protein stabilization; therapeutic antibodies.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies*
  • HIV Infections* / drug therapy
  • HIV Infections* / prevention & control
  • Humans
  • Rats
  • Skin

Substances

  • Antibodies