Oral delivery of biomacromolecules by overcoming biological barriers in the gastrointestinal tract: an update

ABSTRACT

Introduction

Biomacromolecules have proven to be an attractive choice for treating diseases due to their properties of strong specificity, high efficiency, and low toxicity. Besides greatly improving the patient’s complaint, oral delivery of macromolecules also complies with hormone physiological secretion, which has become one of the most innovative fields of research in recent years.

Areas covered

Oral delivery biological barriers for biomacromolecule, transport mechanisms, and various administration strategies were discussed in this review, including absorption enhancers, targeting nanoparticles, mucoadhesion nanoparticles, mucus penetration nanoparticles, and intelligent bionic drug delivery systems.

Expert opinion

The oral delivery of biomacromolecules has important clinical implications; however, these are still facing the challenges of low bioavailability due to certain barriers. Various promising technologies have been developed to overcome the barriers and improve the therapeutic effect of oral biomacromolecules. By considering safety and efficacy comprehensively, the development of intelligent nanoparticles based on the GIT environment has demonstrated some promise in overcoming these barriers; however, a more comprehensive understanding of the oral fate of oral biomacromolecules is still required.

KEYWORDS:

• Oral delivery
• biomacromolecules
• gastrointestinal barriers
• nanoparticles
• intelligent delivery systems

Article highlights

• The complex structure of macromolecules not only confers its good targeting specificity but also leads to poor stability and permeability in the gastrointestinal tract composed of multiple biological barriers.

• The mucus layer and epithelial barrier significantly reduce the mucosal penetration efficiency of most biomacromolecules and conventional drug carriers.

• Various promising oral delivery strategies for overcoming the biological barriers in the gastrointestinal tract for macromolecules were developed, including absorption enhancers, mucosal adhesion or penetration nanoparticles, intelligent drug delivery systems.

• A comprehensive exploration of intelligent drug delivery systems, including biomimetic nanoparticles, environment-responsive nanoparticles, and biomimetic oral microneedles, has greatly increased the feasibility of oral delivery of biomacromolecules.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

National Natural Science Foundation of China (32201135, 31870987) and the Ministry of Science and Technology of the People’s Republic of China.