4.7 Review

Prevention of diabetes-associated fibrosis: Strategies in FcRn-targeted nanosystems for oral drug delivery

Journal

ADVANCED DRUG DELIVERY REVIEWS
Volume 175, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.addr.2021.04.016

Keywords

Antidiabetic peptides; FcRn; IgG; Albumin; Intestinal epithelium; Transcytosis; Half-life; Nanoparticles; Active targeting; Transgenic mouse model

Funding

  1. Portuguese funds through FCT-Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tec-nologia e Ensino Superior [UID/BIM/04293/2019]
  2. Fundacao para a Ciencia e a Tecnologia (FCT), Portugal [SFRH/BD/117598/2016, SFRH/BD/144719/2019]
  3. Research Council of Norway [274993, 287927]
  4. South-Eastern Norway Regional Health Authority [2018052, 2019084]
  5. Fundação para a Ciência e a Tecnologia [SFRH/BD/117598/2016, SFRH/BD/144719/2019] Funding Source: FCT

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Diabetes mellitus poses a risk for fibrosis complications, necessitating controlled symptomatology and innovative oral drug delivery strategies. Targeting drugs to receptors like FcRn in epithelial cells may enhance mucosal absorption and transport, offering new possibilities for oral drug delivery and improved treatment options for diabetes and fibrosis prevention.
Diabetes mellitus is a chronic disease with an elevated risk of micro-and macrovascular complications, such as fibrosis. To prevent diabetes-associated fibrosis, the symptomatology of diabetes must be controlled, which is commonly done by subcutaneous injection of antidiabetic peptides. To minimize the pain and distress associated with such injections, there is an urgent need for non-invasive oral transmucosal drug delivery strategies. However, orally administered peptide-based drugs are exposed to harsh conditions in the gastrointestinal tract and poorly cross the selective intestinal epithelium. Thus, targeting of drugs to receptors expressed in epithelial cells, such as the neonatal Fc receptor (FcRn), may therefore enhance uptake and transport through mucosal barriers. This review compiles how in-depth studies of FcRn biology and engineering of receptor-binding molecules may pave the way for design of new classes of FcRn-targeted nanosystems. Tailored strategies may open new avenues for oral drug delivery and provide better treatment options for diabetes and, consequently, fibrosis prevention. (c) 2021 Elsevier B.V. All rights reserved.

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