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Enhancing Oral Delivery of Biologics: A Non-Competitive and Cross-Reactive Anti-Leptin Receptor Nanofitin Demonstrates a Gut-Crossing Capacity in an Ex Vivo Porcine Intestinal Model.
Masloh, Solene; Chevrel, Anne; Culot, Maxime; Perrocheau, Anaëlle; Kalia, Yogeshvar N; Frehel, Samuel; Gaussin, Rémi; Gosselet, Fabien; Huet, Simon; Zeisser Labouebe, Magali; Scapozza, Leonardo.
Afiliação
  • Masloh S; Blood Brain Barrier Laboratory, Faculty of Science Jean Perrin, Artois University, UR 2465, Rue Jean Souvraz, 62300 Lens, France.
  • Chevrel A; Affilogic, 24 Rue de la Rainière, 44300 Nantes, France.
  • Culot M; School of Pharmaceutical Sciences, University of Geneva, 1 Rue Michel Servet, 1201 Geneva, Switzerland.
  • Perrocheau A; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1 Rue Michel Servet, 1201 Geneva, Switzerland.
  • Kalia YN; Affilogic, 24 Rue de la Rainière, 44300 Nantes, France.
  • Frehel S; Blood Brain Barrier Laboratory, Faculty of Science Jean Perrin, Artois University, UR 2465, Rue Jean Souvraz, 62300 Lens, France.
  • Gaussin R; Affilogic, 24 Rue de la Rainière, 44300 Nantes, France.
  • Gosselet F; School of Pharmaceutical Sciences, University of Geneva, 1 Rue Michel Servet, 1201 Geneva, Switzerland.
  • Huet S; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1 Rue Michel Servet, 1201 Geneva, Switzerland.
  • Zeisser Labouebe M; Affilogic, 24 Rue de la Rainière, 44300 Nantes, France.
  • Scapozza L; Affilogic, 24 Rue de la Rainière, 44300 Nantes, France.
Pharmaceutics ; 16(1)2024 Jan 16.
Article em En | MEDLINE | ID: mdl-38258126
ABSTRACT
Biotherapeutics exhibit high efficacy in targeted therapy, but their oral delivery is impeded by the harsh conditions of the gastrointestinal (GI) tract and limited intestinal absorption. This article presents a strategy to overcome the challenges of poor intestinal permeability by using a protein shuttle that specifically binds to an intestinal target, the leptin receptor (LepR), and exploiting its capacity to perform a receptor-mediated transport. Our proof-of-concept study focuses on the characterization and transport of robust affinity proteins, known as Nanofitins, across an ex vivo porcine intestinal model. We describe the potential to deliver biologically active molecules across the mucosa by fusing them with the Nanofitin 1-F08 targeting the LepR. This particular Nanofitin was selected for its absence of competition with leptin, its cross-reactivity with LepR from human, mouse, and pig hosts, and its shuttle capability associated with its ability to induce a receptor-mediated transport. This study paves the way for future in vivo demonstration of a safe and efficient oral-to-systemic delivery of targeted therapies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article