Abstract
New therapeutic agents such as proteins, peptides, and nucleic acid-based agents are being developed every year, making it vital to find a non-invasive route such as nasal or pulmonary for their administration. However, a major concern for some of these newly developed therapeutic agents is their poor absorption. Therefore, absorption enhancers have been investigated to address this major administration problem. This paper describes the basic concepts of transmucosal administration of drugs, and in particular the use of the pulmonary or nasal routes for administration of drugs with poor absorption. Strategies for the exploitation of absorption enhancers for the improvement of pulmonary or nasal administration are discussed, including use of surfactants, cyclodextrins, protease inhibitors, and tight junction modulators, as well as application of carriers such as liposomes and nanoparticles.
Highlights
Absorption enhancers are functional excipients included in formulations to improve the absorption of drugs across biological barriers
All protease inhibitors were effective in reducing insulin degradation and these findings suggest that combination of absorption enhancers and protease inhibitors would be a useful approach for improving the pulmonary absorption of biologically active drugs
The results showed that treatment with a 0.1% G3 PAMAM dendrimer could increase the secretion of organic cation transporters (OCTs), OCT1, OCT2, and OCT3, which might be related to the absorption-enhancing mechanisms of the pulmonary absorption of the macromolecule
Summary
Absorption enhancers are functional excipients included in formulations to improve the absorption of drugs across biological barriers. In nasal and pulmonary administration, absorption enhancers have been investigated over the last two decades, to increase the rate of absorption by targeting different mechanisms [5,6] These mechanisms are either to improve the permeation of materials across the epithelial barrier via intracellular or paracellular mechanisms (Figure 1) or to enhance stability and mucus solubility of the drugs regionally. To date, no safe absorption enhancer for pulmonary administration of drugs has translated into commercial products Their use has generated safety concerns due to potential irreversible alteration of the epithelial cell membrane, which could potentially make the lung susceptible to the entry of exogenous allergens. TThhiiss rreevviieeww ccrriittiiccaallllyy aasssseesssseess aaddvvaanncceess iinn tthhee fifieelldd ooff aabbssoorrppttiioonn eennhhaanncceerrss ffoorr nnaassaall aanndd ppuullmmoonnaarryy ddrruugg aaddmmiinniissttrraattiioonn.
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