ABSTRACT

The development of drug delivery systems based on the lipid uptake and lipoprotein pathways requires specialized methodologies from the pharmaceutical, biological, and synthetic chemistry disciplines. This chapter describes some of the methodologies which the authors have found useful in lipid/lipoprotein transport studies and in the development of lymphatic- or lipoprotein-based drug delivery systems. There are numerous experimental methodologies and protocols which have been reported for the assessment of lymphatic transport in the rat. A complication which may be associated with interpretation of intestinal lymphatic transport data based on thoracic lymph levels is that the presence of lipoproteins within the lymph system may facilitate the exchange of drugs between the general circulation and the lymphatics. In an anesthetized mesenteric lymph duct cannulated rat model, the intestinal lymphatic transport of DDT was increased by a factor of approximately twofold when the period of fasting after cannulation was varied between 2 and 48 hr.