New insights into nanomedicines for oral delivery of glucagon‐like peptide‐1 analogs

Author:

Pinto Soraia Filipa Tavares12ORCID,Santos Hélder Almeida345ORCID,Sarmento Bruno Filipe Carmelino Cardoso16ORCID

Affiliation:

1. Instituto de Investigação e Inovação em Saúde (i3S) University of Porto Porto Portugal

2. Instituto de Ciências Biomédicas Abel Salazar (ICBAS) University of Porto Porto Portugal

3. Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy University of Helsinki Helsinki Finland

4. W.J. Kolff Institute for Biomedical Engineering and Materials Science University Medical Center Groningen, University of Groningen Groningen The Netherlands

5. Department of Biomedical Engineering University Medical Center Groningen, University of Groningen Groningen The Netherlands

6. Instituto Universitário de Ciências da Saúde (IUCS‐CESPU) Gandra Portugal

Abstract

AbstractType 2 diabetes mellitus (T2DM) is a metabolic disorder that arises when the body cannot respond fully to insulin, leading to impaired glucose tolerance. Currently, the treatment embraces non‐pharmacological actions (e.g., diet and exercise) co‐associated with the administration of antidiabetic drugs. Metformin is the first‐line treatment for T2DM; nevertheless, alternative therapeutic strategies involving glucagon‐like peptide‐1 (GLP‐1) analogs have been explored for managing the disease. GLP‐1 analogs trigger insulin secretion and suppress glucagon release in a glucose‐dependent manner thereby, reducing the risk of hyperglycemia. Additionally, GLP‐1 analogs have an extended plasma half‐life compared to the endogenous peptide due to their high resistance to degradation by dipeptidyl peptidase‐4. However, GLP‐1 analogs are mainly administered via subcutaneous route, which can be inconvenient for the patients. Even considering an oral delivery approach, GLP‐1 analogs are exposed to the harsh conditions of the gastrointestinal tract (GIT) and the intestinal barriers (mucus and epithelium). Hereupon, there is an unmet need to develop non‐invasive oral transmucosal drug delivery strategies, such as the incorporation of GLP‐1 analogs into nanoplatforms, to overcome the GIT barriers. Nanotechnology has the potential to shield antidiabetic peptides against the acidic pH and enzymatic activity of the stomach. In addition, the nanoparticles can be coated and/or surface‐conjugated with mucodiffusive polymers and target intestinal ligands to improve their transport through the intestinal mucus and epithelium. This review focuses on the main hurdles associated with the oral administration of GLP‐1 and GLP‐1 analogs, and the nanosystems developed to improve the oral bioavailability of the antidiabetic peptides.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Funder

Fundação para a Ciência e a Tecnologia

Publisher

Wiley

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