Strategies and industrial perspectives to improve oral absorption of biological macromolecules

ABSTRACT

Introduction: Therapeutic proteins have become a highly attractive drug of choice due to minimal toxicity, high activity and exquisite specificity. Oral delivery of protein drugs is a very interesting area for research, and, naturally, numerous technologies are required to improve the oral bioavailability of therapeutic proteins.

Areas covered: This review article systemically generalized the major physiological barriers facing oral macromolecule delivery as well as the current approaches and novel developments in the field, including permeation enhancers, enzyme inhibitors, particulate drug delivery system, ligand delivery system, mucoadhesive delivery system, mucus penetration delivery system and other strategies.

Expert opinion: The development of composite formulation methods need to meet regulatory requirements for reproducibility, manufacturing cost, and bioavailability. So far, oral delivery of protein and peptide drugs is still facing immense challenges despite of the fact that some clinical studies are undergoing. The most advanced clinical strategies for therapeutic proteins are co-administration of absorption enhancers or protease inhibitors. Besides, rising new technologies in the field also provides a growing opportunity, such as nanotechnology, mucoadhesive and mucus penetration particulate delivery system.

KEYWORDS:

• Gastrointestinal barriers
• nanoparticles
• oral delivery
• peptides
• proteins

Article highlights

• Theoretical basis of the gastrointestinal tract and related barriers are provided.

• The transport mechanisms of macromolecules across intestinal epithelia are discussed.

• Novel pharmaceutical approaches to enhance macromolecules peroral absorption are presented.

• Recently developed formulations in clinical stages are introduced.

• Challenges and newly emerging technologies within this field are discussed.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by the Distinguished Professor Project of Liaoning Province (2015).