However, all oral formulations are still at an early stage for the treatment of systemic fungal infections. Most of groups appear to have abandoned their research after publishing a single paper in which oral delivery vehicles have been shown to improve therapeutic efficacy. To our knowledge, most studies have remained at experimental research, lacking clinical potential. Only one group from the University of British Columbia has continued to pursue development of an oral AmB formulation over many years and published a series of papers. They have successfully developed two lipid-based formulations for oral administration. One is an oral emulsion composed of Peceol® and DSPE-PEG; the other is an oral cochleate composed of negatively charged phospholipid and calcium cations. The oral emulsion gave a favorable outcome that increased intestinal absorption of AmB, directly leading to patent acquisition by iCo Therapeutics Inc. (Vancouver, BC, Canada). The oral cochleate is currently in development by BioDelivery Sciences, Inc. (Raleigh, NC), who published results of a Phase I trial in February 2009 showing a positive therapeutic effect equivalent to IV therapy. However, it is unknown whether the two lipid-based formulations could progress to the market because further clinical data have not been reported. According to the current findings, cubosomes with a lipid composition and liquid crystalline structure have been developed to enhance the oral bioavailability of AmB, showing a better therapeutical effect on fungal infection in vivo. Unfortunately, there are many difficulties in the development of AmB-loaded cubosomes as a practicable oral drug delivery system. As mentioned previously, the design, selection, and development of drug delivery systems require in-depth understanding of the behavior of a drug under physiological conditions and of its physicochemical properties. However, there is still limited knowledge of how to increase AmB oral bioavailability. It remained difficult to select and design an appropriate drug delivery system to improve AmB oral absorption. Perhaps, some novel drug delivery system will emerge that can be used to develop an effective oral formulation of AmB. In spite of the difficulties, these lipid formulations may have better prospects compared to other drug delivery systems currently known. resource:https://www.tandfonline.com/doi/full/10.1080/10717544.2016.1225852
