Circumventing the gastrointestinal barrier for oral delivery of therapeutic proteins and peptides (PPTs): current trends and future trajectories

Lily Ellysa Hashim, Akmal Hidayat Sabri, Malihah Athirah Mohamad, Qonita Kurnia Anjani, Mohd Faiz Mustaffa, Khuriah Abdul Hamid

Research output: Contribution to journalArticlepeer-review


Therapeutic proteins and peptides (PPTs) have become one of the most important biological molecules for the management of many common and complex diseases due to their high specificity and high bioactivity. However, these biomolecules are mainly given by the hypodermic injection, which often leads to poor patient compliance due to the invasive nature of this route of administration. The oral route has been considered the most convenient and patient-friendly route for drug delivery relative to hypodermic injection. Despite the ease and simplicity conferred by oral administration, this drug delivery route suffers rapid peptide degradation in gastric fluid and low intestinal uptake. In order to circumvent these issues, several strategies, such as enzyme inhibitors, permeation enhancers, chemical modification, mucoadhesive and stimuli-responsive polymers, and specialised particulate formulation have been developed. Such strategies are designed with the aim of protecting proteins and peptides from the harsh gastrointestinal environment as well as providing a strategy to enhance the uptake of the therapeutic across the gastrointestinal tract. This review aims to provide an overview of the current development in enteral drug delivery strategies for proteins and peptides. The design of these drug delivery systems in overcoming physical and chemical barriers along the gastrointestinal tract while improving oral bioavailability will be highlighted and discussed.
Original languageEnglish
JournalCurrent drug delivery
Issue number10
Early online date18 Apr 2023
Publication statusEarly online date - 18 Apr 2023


  • Pharmaceutical Science


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