Monday, March 17, 2008

Liposomes: Facts vs. Propaganda

If you found your way here through the Encapsula web site, you have probably already read our primer on liposomes and liposome technology. We have seen some very nice and accurate descriptions of the same on other web sites which often include excellent graphics which are really the key in being able to visualize and understand the concept. Unfortunately many of these sites, while very accurate about their general description of liposome technology, tend to completely misinterpret the specific details of liposome biophysical and physiological behavior. Although a more recent review of these websites reveals that the most spectacular, and unproven, of the promises (98-100% intestinal absorption of liposomal encapsulated water-soluble compounds) have been removed from the websites, there is still a reference to the entire liposome being absorbed along with its contents into the bloodstream. There is currently no reputable scientific evidence that this occurs. Other sites have made similar claims about topically applied liposomes. Again, this has not been reported and reproduced in the scientific literature to date.

When injected intravenously, liposomes produce a very distinctive biodistribution that is typical of any particulate matter that is injected directly into the bloodstream. The reticulo-endothelial system (macrophages located primarily in the liver, spleen and lungs), or RES, will endocytose the liposomes. Water-soluble compounds and drugs show no such preference for the RES. Depending on the size, type, lipid composition and surface modifications of the liposomes however, the pharmacokinetic profile and relative uptake of liposomes among these organs can be dramatically altered. A small proportion of a dose of so-called “stealth” liposomes and other small liposomes with various surface modifications can be directed to sites of inflammation such as that found with focal infections, arthritic joints and tumors, but the majority of the dose of these liposomes will also end up in the RES with time. Therefore if liposomes were absorbed intact into the bloodstream via oral or topical delivery, the liposomes would collect in the RES just as if they were injected intravenously. We have not seen this data from either orally dosed or topically applied liposomes. Needless to say, this data, if it existed or is produced in the future, will create quite a stir in both the liposome and general drug delivery communities.

This is not to say that there has not been successful delivery of water-soluble compounds, namely calcitonin and insulin (Takeuchi, et al), by orally dosed liposomes in rats. However, the authors report that they do not find intact liposomes in the bloodstream. These liposomes are also specially formulated to withstand the acid environment of the stomach plus are surface modified in order to adhere to the intestinal wall. While this thorough and impressive research represents a major breakthrough in liposomology, it does not show that liposomes pass through the intestinal wall into the bloodstream, especially not the generic phosphatidylcholine liposomes which are used in the products advertised by some companies on the internet.

The data on topical delivery by liposomes varies dramatically depending on the compound being delivered and the type of liposome used as well as the intended delivery site. Fat-soluble compounds such as steroids which can be delivered topically by other methods also can be delivered by liposomes with some reports in the literature of that delivery being enhanced. However, there does not yet appear to be an efficient liposomal system for delivering water-soluble compounds to the bloodstream, although there is at least one liposome company devoted to this effort.

New and exciting science in all fields including liposomology is reported every day. If you find scientific articles on non-intravenous delivery of liposomes to the bloodstream that refutes the above statements, we invite you to post a review of the paper. Just remember, the key is demonstrating that the liposomes appear in the RES in order to claim that intact liposomes are indeed entering the bloodstream by the alternative route.