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Review
. 2021 Mar 25;22(7):3349.
doi: 10.3390/ijms22073349.

Delivery of Orally Administered Digestible Antibodies Using Nanoparticles

Toshihiko Tashima  1
Affiliations
Review

Delivery of Orally Administered Digestible Antibodies Using Nanoparticles

Toshihiko Tashima. Int J Mol Sci. .

Abstract

Oral administration of medications is highly preferred in healthcare owing to its simplicity and convenience; however, problems of drug membrane permeability can arise with any administration method in drug discovery and development. In particular, commonly used monoclonal antibody (mAb) drugs are directly injected through intravenous or subcutaneous routes across physical barriers such as the cell membrane, including the epithelium and endothelium. However, intravenous administration has disadvantages such as pain, discomfort, and stress. Oral administration is an ideal route for mAbs. Nonetheless, proteolysis and denaturation, in addition to membrane impermeability, pose serious challenges in delivering peroral mAbs to the systemic circulation, biologically, through enzymatic and acidic blocks and, physically, through the small intestinal epithelium barrier. A number of clinical trials have been performed using oral mAbs for the local treatment of gastrointestinal diseases, some of which have adopted capsules or tablets as formulations. Surprisingly, no oral mAbs have been approved clinically. An enteric nanodelivery system can protect cargos from proteolysis and denaturation. Moreover, mAb cargos released in the small intestine may be delivered to the systemic circulation across the intestinal epithelium through receptor-mediated transcytosis. Oral Abs in milk are transported by neonatal Fc receptors to the systemic circulation in neonates. Thus, well-designed approaches can establish oral mAb delivery. In this review, I will introduce the implementation and possibility of delivering orally administered mAbs with or without nanoparticles not only to the local gastrointestinal tract but also to the systemic circulation.

Keywords: drug delivery system; mouth-to-systemic circulation monoclonal antibody delivery; nanodelivery; neonatal Fc receptor-mediated transcytosis; oral immunotherapy; orally administered monoclonal antibodies.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
The position of digestive organs.
Figure 2
Figure 2
Pattern diagram of the small intestinal surface.
Figure 3
Figure 3
Structure of cyclosporine as N-methylated macropeptide.
Figure 4
Figure 4
Structures of IgG and its fragments such as Fc, Fab, and F(ab′)2.
Figure 5
Figure 5
Schematic overview of transcytosis or salvation pathway of IgG through FcRn binding.
Figure 6
Figure 6
Schematic overview of transcytosis of albumin through megalin–cubilin and FcRn binding.
See this image and copyright information in PMC

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