Recent advances in mucus-penetrating nanomedicines for oral treatment of colonic diseases

ABSTRACT

Introduction

Oral administration is the most common route for treating colonic diseases that present increased incidences in recent years. Colonic mucus is a critical rate-limiting barrier for the accumulation of oral therapeutics in the colonic tissues. To overcome this obstacle, mucus-penetrating nanotherapeutics have been exploited to increase the accumulated amounts of drugs in the diseased sites and improve their treatment outcomes against colonic diseases.

Areas covered

In this review, we introduce the structure and composition of colonic mucus as well as its impact on the bioavailability of oral drugs. We also introduce various technologies used in the construction of mucus-penetrating nanomedicines (e.g. surface modification of polymers, physical means and biological strategies) and discuss their mechanisms and potential techniques for improving mucus penetration of nanotherapeutics.

Expert opinion

The mucus barrier is often overlooked in oral drug delivery. The weak mucus permeability of conventional medications greatly lowers drug bioavailability. This challenge can be addressed through physical, chemical and biological technologies. In addition to the reported methods, promising approaches may be discovered through interdisciplinary research that further helps enhance the mucus penetration of nanomedicines.

KEYWORDS:

• Mucus penetration
• nanomedicines
• oral administration
• inflammatory bowel disease
• colon cancer

Article highlights

• Gel-like colonic mucus is composed of mucins, a glycoprotein with hydrophobic domains at both ends and a hydrophilic glycosylated backbone.

• Small sizes, neutral charges and hydrophilic oleophobic surfaces are important factors for nanoparticles (NPs) to penetrate through mucus layer.

• Oral drug delivery is advantageous for treating colonic diseases due to its high patient compliance and direct targeting to the diseased sites.

• Some polymers, such as polyethylene glycol, zwitterion and perfluorochemical, have been applied to enhance mucus penetration of NPs.

• Nanomotors have been exploited to improve drug bioavailability by actively penetrating the mucus layer using internal or external driving forces.

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 of this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China [82072060], the Open Fund of State Key Laboratory of Southwestern Chinese Medicine Resources [SKLTCM2022067], the Science and Technology Department of Jiangxi Province [20212BDH81019 and 20224BAB206073], the Fundamental Research Funds for the Central Universities [SWU-XDPY22006], the Venture & Innovation Support Program for Chongqing Overseas Returnees [2205012980212766], the Distinguished Young Scholars of Chongqing [2022NSCQ-JQX5279], and the Natural Science Foundation Project of Chongqing [cstc2020jcyj-msxmX0292].