Theranostics 2022; 12(3):1419-1439. doi:10.7150/thno.61747 This issue


Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies

Guanyu Chen1, Weirong Kang2, Wanqiong Li1, Shaomeng Chen1, Yanfeng Gao1✉

1. School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.
2. Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

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Chen G, Kang W, Li W, Chen S, Gao Y. Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies. Theranostics 2022; 12(3):1419-1439. doi:10.7150/thno.61747. Available from

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Graphic abstract

The past few years has witnessed a booming market of protein and peptide drugs, owing to their superior efficiency and biocompatibility. Parenteral route is the most commonly employed method for protein and peptide drugs administration. However, short plasma half-life protein and peptide drugs requires repetitive injections and results in poor patient compliance. Oral delivery is a promising alternative but hindered by harsh gastrointestinal environment and defensive intestinal epithelial barriers. Therefore, designing suitable oral delivery systems for peptide and protein drugs has been a persistent challenge. This review summarizes the main challenges for oral protein and peptide drugs delivery and highlights the advanced formulation strategies to improve their oral bioavailability. More importantly, major intestinal cell types and available targeting receptors are introduced along with the potential strategies to target these cell types. We also described the multifunctional biomaterials which can be used to prepare oral carrier systems as well as to modulate the mucosal immune response. Understanding the emerging delivery strategies and challenges for protein and peptide drugs will surely inspire the production of promising oral delivery systems that serves therapeutic needs in clinical settings.

Keywords: Protein and peptide drug, Oral delivery system, Physical and biochemical barrier, Intestinal mucosa, Intestinal cell targeting, Oral bioavailability.