Oral Delivery Strategies for Biological Drugs.

Abstract

Biologics have low toxicity and are highly specific and biocompatible, offering advantages over small-molecule drugs. The administration of biologics in oral form provides a significant benefit in improving patient compliance. However, oral administration faces the challenge of a harsh gastrointestinal environment, including low pH, enzyme degradation, and poor intestinal epithelium permeability, which limits the bioavailability of biologics. As a result, the administration of biologics remains primarily in the parenteral form. This review introduces the physiological barriers encountered by oral biologics delivery, describes the oral biologics currently on the market or under clinical trials, as well as oral biologics-based technologies, and discusses the recent progress on novel oral delivery technologies such as nanoparticle-delivery systems, ionic liquids, and microneedles. Specifically, colon-targeted approaches for oral biologics delivery are also explored, as the colon could be a more optimal absorption site due to having less diverse proteolytic enzymes and relatively limited digestibility compared to the upper gastrointestinal tract (GIT). Lastly, the future research directions for oral biologics are highlighted and it is concluded that with an in-depth study of biological drugs and advancement in delivery methods, oral biologics can pioneer new opportunities.