Optimising oral systems for the delivery of therapeutic proteins and peptides

Abstract

Therapeutic proteins/peptides are mostly administered as parenteral (injectable) preparations as a result of their poor oral bioavailability which is due to degradation by proteolytic enzymes, poor membrane permeability and large molecular size. However, the oral route would be preferred to the parenteral administration because it is more convenient for self-administration, non-invasive and more patient friendly. Consequently, efforts have intensified over the past two decades to maximize the extent of absorption of protein and peptide drugs in order to achieve optimum bioavailability via the oral route. A suitable oral delivery system should retain the drug and maintain its integrity until it gets to the region of maximum absorption where the protein/peptide is released. It would be advantageous for such a delivery system to be capable of attaching itself to the absorptive cells in that region during the course of drug release by means of specific interactions with the tissue components. Furthermore, movement of drug should be independent of prevailing factors in the gut during passage. This review examines the various efforts and strategies that have been used to pursue the goals of effective oral peptide delivery, progress made so far, as well as current trends and future prospects. Relevant issues and phenomena such as membrane permeability control, intestinal absorption, paracellular pathway and targeting have also been discussed.

Meta‐Analysis for Correlating Structure of Bioactive Peptides in Foods of Animal Origin with Regard to Effect and Stability

“…The paracellular route is usually inaccessible to peptides due to the existence of the tight junctions between enterocytes (Assimakopoulos, Papageorgiou, & Charonis, 2011;Stevenson & Keon, 1998). However, permeability of this tight junction is dependent on Ca 2+ levels and is different for different epithelia; thus, permeability of tight junctions can be altered temporarily to allow flow of water-soluble compounds (Arhewoh, Ahonkhai, & Okhamafe, 2005).The preferred route is dependent on the number of AA residues in the bioactive peptide. Peptides with 2 or 3 AA residues might be absorbed into enterocytes utilizing the PepT1 transporter (Brodin, Nielsen, Steffansen, & Frokjaer, 2002) or in renal epithelia via either PepT1 or the additional PepT2 transporter (Yang, Dantzig, & Pidgeon, 1999).…”

Intracellular sorting of differently charged chitosan derivatives and chitosan-based nanoparticles

“…[1][2][3][4] However, only a limited number of NPs have reached preclinical and clinical studies partly because of a poor understanding of their behavior both in vivo and in vitro. [1][2][3][4] However, only a limited number of NPs have reached preclinical and clinical studies partly because of a poor understanding of their behavior both in vivo and in vitro.…”

Oral Delivery of Protein/Peptide Therapeutics

“…In addition, a combination of these approaches can further maximize the overall drug bioavailability. Those approaches have been described in a number of excellent review articles that readers are referred to for additional details (Jain, 2001;Sood and Panchagnula, 2001;Adessi and Sotto, 2002;Shah et al, 2002;Lambkin and Pinilla, 2002;Lee, 2002;Mahato et al, 2003;Arhewoh et al, 2005;Hamman et al, 2005;Rick, 2005;Mustata and Dinh, 2006;Kumar et al, 2006;Morishita and Peppas, 2006;Semalty et al, 2007;Shaji and Patole, 2008;Shingh et al, 2008;Ghilzai, 2006).…”