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. 2009 Nov 16;64(22):4553-4565.
doi: 10.1016/j.ces.2009.04.050.

Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents

Nicholas A Peppas  1 , Daniel A Carr
Affiliations

Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents

Nicholas A Peppas et al. Chem Eng Sci. .

Abstract

The combination of materials design and advances in nanotechnology has led to the development of new therapeutic protein delivery systems. The pulmonary, nasal, buccal and other routes have been investigated as delivery options for protein therapy, but none result in improved patient compliances and patient quality of life as the oral route. For the oral administration of these new systems, an understanding of protein transport is essential because of the dynamic nature of the gastrointestinal tract and the barriers to transport that exist.Models have been developed to describe the transport between the gastrointestinal lumen and the bloodstream, and laboratory techniques like cell culture provide a means to investigate the absorption and transport of many therapeutic agents. Biomaterials, including stimuli-sensitive complexation hydrogels, have been investigated as promising carriers for oral delivery. However, the need to develop models that accurately predict protein blood concentration as a function of the material structure and properties still exists.

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Figures

Figure 1
Figure 1
Drug levels in the blood with (—) traditional repeated dosing and (----) controlled delivery dosing.
Figure 2
Figure 2
Potential barriers to solute transport in a cell culture system. (A) Cell monolayer system grown onto a microporous system. (B) Concentration profile system for the solute with the largest concentration drop within the cell monolayer. Co, original concentration of the solute, Cd, concentration of the solute in the donor chamber, Cr, concentration of the solute in the receiver chamber
Figure 3
Figure 3
Transport pathways through the cell monolayer
Figure 4
Figure 4
Comparison of absorptive surface areas for drugs in the intestine in vivo and in Caco-2 monolayers.
Figure 5
Figure 5
Comparison of absorptive surface areas for high and low permeability drugs.
Figure 6
Figure 6
Anionic complexation hydrogel swelling behavior as a function of the pH of the gastrointestinal tract.
See this image and copyright information in PMC

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