Abstract
Overcoming the gastrointestinal (GI) barriers is a formidable challenge in the oral delivery of active macromolecules such as peptide- and protein- based drugs. In the past four decades, a plethora of formulation strategies ranging from permeation enhancers, nanosized carriers, and chemical modifications of the drug's structure has been investigated to increase the oral absorption of these macromolecular compounds. However, only limited successes have been achieved so far, with the bioavailability of marketed oral peptide drugs remaining generally very low. Recently, a few approaches that are based on physical interactions, such as magnetic, acoustic, and mechanical forces, have been explored in order to control and improve the drug permeability across the GI mucosa. Although in the early stages, some of these methods have shown great potential both in terms of improved bioavailability and spatiotemporal delivery of drugs. Here, we offer a concise, yet critical overview of these rather unconventional technologies with a particular focus on their potential and possible challenges for further clinical translation.
Highlights
Oral administration is one of the oldest and most convenient modes of drug delivery, yet still unresolved challenges lead to the continuous development of novel formulation strategies [1]
The molecular weight and physicochemical nature of these compounds often preclude their efficient permeation through the GI tract [15], which emphasizes the need for other oral drug delivery strategies
There was no significant difference in insulin bioavailability reported for these two types of formulations, i.e. both ranged from 1.3% to 1.9% relative to subcutaneous (s.c.) injection
Summary
Oral administration is one of the oldest and most convenient modes of drug delivery, yet still unresolved challenges lead to the continuous development of novel formulation strategies [1]. The approval of orally delivered glucagon-like peptide-1 receptor agonist, semaglutide, highlights the recent success in the pursuit of permeation enhancers to promote the absorption of peptides and proteins in the gastrointestinal (GI) tract [8,9,10] Despite these encouraging developments, the oral delivery strategies for macromolecular drugs still lag far behind the rapid advancement of biologics [11,12] and other new pharmacological modalities, such as the proteolysis targeting chimera (PROTAC) [13] and the RNAs therapeutics [14]. Instead of depending on the passive or receptor-mediated transport of active pharmaceutical ingredients (APIs), the proposed devices rely on magnetic, mechanical, electrochemical, and acoustic forces to enhance absorption [24,25] Still in their infancy, some of these strategies have shown great potential prompting their clinical development. A particular attention is paid to the relative efficiency of these formulation approaches in improving the oral bioavailability of poorly permeable drugs as well as the challenges and safety concerns associated with their clinical translatability
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