Drug absorption macromolecules

McMartin C, Hutchinson LE, Hyde R, Peters GE (1987) Analysis of structural requirements for the absorption of drugs and macromolecules from the nasal cavity. J Pharm Sci 76 535-540. 

Epithelial cells migrate from the crypts to the tips of the villi in about 2 days [11]. During this time they differentiate and, at the end of their life cycle, are shed into the lumen. Their contents are extruded in the succus entericus and the intracellular enzymes become available for food and drug metabolization in the gut. The amount of cellular material liberated is about 250 g per day. Drugs and macromolecules can be absorbed by this first paracellular pathway, but no quantitative data are as yet available concerning the extent of this phenomenon. Recent literature suggests that some authors are in favor of absorption between the cells, called persorption and responsible for the uptake of cells [15], while others are still skeptical. 

Purity for a small molecule is a relatively simple concept. Normally, an HPLC method is sufficient to measure the content and impurity levels of a small molecule drug. A macromolecule, such as a protein, has a much more complex behavior. Determining protein concentration by UV absorption spectroscopy can give a measure of the total protein in the product, but it will not necessarily differentiate between active protein and inactive protein (i.e., denatured or otherwise degraded). A validated method or methods to determine the biological activity of the molecule is needed. So, whereas protein concentration is usually tested as part of the specifications, it is also normally accompanied by one or more methods that measure or correlate to biological activity. This is the bioassay. These methods can be animal-based or cell-based, protein interaction assays, binding methods such as surface plas-mon resonance or ELISA (enzyme-linked immunosorbent assay) and immunoblot methods. 

The absorption of drugs from the rectal [32] cavity has been studied in some detail. Muranishi et al. [34] have shown that a significant increase in the absorption and lymphatic uptake of soluble and colloidal macromolecules can be achieved by pretreating the rectal mucosal membrane with lipid-nonionic surfactant mixed micelles. They found no evidence of serious damage of the mucosal membrane. Davis [30] suggested that the vaginal cavity could be an effective delivery site for certain pharmaceuticals, such as calcitonin, used for the treatment of postmenopausal osteoporosis. 

M. Murakami, Enhanced absorption and lymphatic transport of macromolecules via the rectal route, in Delivery Systems for Peptide Drugs (S. S. Davis, L. Ilium, and E. Tomlinson, eds.), Plenum Press, New York, 1986, p. 177. 

Patton, J. 1996. Mechanisms of macromolecule absorption by the lungs. Advanced Drug Delivery Reviews 19, 3-36. 

---