ROS-responsive microneedles loaded with integrin avβ6-blocking antibodies for the treatment of pulmonary fibrosis

  • J Control Release. 2023 Aug;360:365-375. doi: 10.1016/j.jconrel.2023.03.060.
Hao Ding  1 ,  Yuan Cui  1 ,  Jian Yang  1 ,  Yu Li  1 ,  Hongtao Zhang  2 ,  Sheng Ju  1 ,  Xingyu Ren  3 ,  Cheng Ding  4 ,  Jun Zhao  5
Affiliations
  • 1. Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, China.
  • 2. Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou 215000, China.
  • 3. Department of Medical imaging, College of Clinical Medicine, Suzhou Vocational Health College, Suzhou 215000, China.
  • 4. Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, China. Electronic address: [email protected].
  • 5. Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, China. Electronic address: [email protected].
PMID: 37331606 DOI: 10.1016/j.jconrel.2023.03.060
Abstract

Pulmonary fibrosis (PF) is a fibrotic interstitial pneumonia with poor prognosis and limited treatment methods. Inhibition of Integrin αVβ6 expression could prevent pulmonary fibrosis, however, a phase II clinical trial of αVβ6-blocking antibody treating PF stopped prematurely due to low bioavailability and toxic side effects of systematic administration. Here, we describe a micro-invasive percutaneous transthoracic and hydrogen peroxide-responsive microneedle composed of degradable gel for smart delivery of Integrin αvβ6-blocking antibody which has the advantages of rapid response, excellent biocompatibility, protection of bioactivity, high tissue permeation and specific targeting to lesions. This microneedle could partially release Integrin αvβ6-blocking antibodies when exposed to hydrogen peroxide generated during PF, thus reducing activation of the pro-fibrotic factor TGF-β1 from its latent precursor and showing excellent therapeutic efficacy for PF.

Keywords
Drug delivery; Integrin αvβ6; Microneedle; Minimally invasive surgery; Pulmonary fibrosis.
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