Mixed micelles drug absorption

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. 

In addition to improving drug absorption, permeation enhancers that form mixed micelles with peptides or proteins may also provide protection against metabolic processes, including protease-dependent inactivation, efflux transport, and protein denaturation, all of which could lead to reduced bioavailabUity. A permeation enhancer that may also inhibit some competing metabolic processes could greatly improve the poor and inconsistent bioavailabiUty of some short and cyclic polypeptides such as cyclosporine (11 aa cyclic peptide) (Figure 13.11). 

Muranishi, S., N. Muranishi, and H. Sezaki. 1979. Improvement of absolute bioavailability of normally poorly absorbed drugs Inducement of the intestinal absorption of streptomycin and gentamicin by lipid-bile salt mixed micelles in rat and rabbit. Int J Pharm 2 101. 

Muranishi, N., et al. 1980. Mechanism for the inducement of the intestinal absorption of poorly absorbed drugs by mixed micelles. I. Effects of various lipid-bile salt mixed micelles on the intestinal absorption of streptomycin in rat. Int J Pharm 4 271. 

Mixed micelles consist of fatty acids solubilized by surfactants or bile salts. The effects of mixed micelles on drug absorption were reviewed by Muranishi Mixed micelles are effective absorption enhancers for compounds such as heparin, streptomycin, gentamycin, and insulin. The effect of mixed micelles on drug absorption tends to be greater at the distal region of the GI tract. The mechanism for increased absorption is not known. Some publications claim that they are safe to use. Others report a disordering effect on intestinal epithelial cells. 

The inclusion of a surfactant in the suppository formulation may enhance the rectal absorption of drugs. The effect has been attributed to the formation of mixed micelles. It has been suggested that the presence of the micelle facilitates the incorporation of the lipid component of the mixed micelle into the biological membrane. This lipid then enhances the fluidity and permeability of the membrane to the poorly absorbed drug. It appears that the colorectal mucous membrane is more sensitive to the effects of mixed micelles than the gastrointestinal membrane of the small intestine. 

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