Particulate-carrier systems

A notable property of liposomes, which has not been appreciated enough, is the presence of water inside liposomes. This makes them an excellent delivery system for biotechnologically engineered proteins with tertiary and quanternary structures which are sensitive to irreversible damage induced by dehydration, as often occurs with alternative, particulate carrier systems. 

Therefore, no detailed discussion on the interaction of any liposomes with any particular cell type should be stated here. We refer to several recent publications for a study of interaction of DOPE CHEMS liposomes and COS-7 and HUVEC (109) and for a study on size-dependent uptake of particles into B16-F10 (72). The combination of flow cytometry and a microscopic method (e.g., spectral bio-imaging) turned out to be highly useful both to study the initial mode of internalization and to follow the intracellular fate of liposomes and other particulate carrier systems. 

Oechslein, C.R., Fricker, G., and Kissel, T., Nasal delivery of octreotide Absorption enhancement by particulate carrier systems, 7 t. J. Pharm., 139 25-32 (1996). 

D. J. A. Crommelin, G. Scherphof, and G. Storm, Active targeting with particulate carrier systems in the blood compartment, Adv. Drug Deliv. Rev. 17 49-60 (1995). 

In addition to the issue of endothelial permeability, the effect of macrophages in direct contact with the blood circulation (e.g. Kupffer cells in the liver) on the disposition of carrier systems must be considered. Unless precautions are taken, particulate carrier systems are readily phagocytosed by these macrophages and tend to accumulate in these cells. Phagocytic uptake by the cells of the mononuclear phagocyte systems (MPS also sometimes known as the reticuloendothelial system, RES) has been described in Chapter 1 (Section 1.3.3.2). The MPS comprises both ... 

Other participate carrier systems Other particulate carrier systems which are under evaluation include ... 

A particular carrier system containing a cytotastic dmg is rapidly taken up by the MPS upon intravenous injection. How can one realistically extend the blood circulation time of this particulate carrier system keeping in mind that this system should be used in patients ... 

Liposomes belong to the most studied particulate carrier systems. In the past decades, a vast number of liposome preparation methods for the encapsulation of a large variety of molecules have been developed and refined. We refer to the corresponding literamre and to our publications for more information. We recommend the high pressure filter extrusion method for the preparation of peptide or DNA containing liposomes because of its ease, versatility, up-scaling options and high quality of the liposomes produced. 

One approach where the characteristics of the liposomal carrier system are well matched to the intended therapeutic application is the delivery of drugs to the MPS. Because of their particulate nature, the major route of clearance of liposomes, when administered in vivo by a variety of routes, is phagocytosis by MPS cells, especially macrophages in liver and spleen. Obviously, this "natural" fate of liposomes in vivo is an advantage if one attempts to treat diseases... 

The various particulate drug-carrier systems that have been investigated can be grouped into the following classes ... 

D. Meisner, Liposomes as a pulmonary drug delivery system, Pharmaceutical Particulate Carriers, (A. Rolland, ed.), Marcel Dekker, New York, 1993, p. 31. 

The process of phagocytosis is of particular relevance when particulate delivery systems, such as microspheres, liposomes and other advanced delivery systems (described in Chapter 5), are used. Such particulate carriers are susceptible to MPS clearance. Sequestration by the MPS is useful in some cases, for example in the treatment of certain microbial diseases. However, if the drag is to be delivered to sites other than the MPS, it is highly undesirable. Therefore considerable research effort is being directed towards methods of avoiding MPS uptake of drag delivery systems. Strategies to both exploit and avoid MPS uptake are described in detail in Chapter 5 (see Section 5.1.4). 

The development of liposomal systems has thus contributed greatly to the development of drag carrier systems in general and has highlighted the various pharmaceutical hurdles that must be overcome before a DOTS can reach the marketplace. In addition, liposomal development has provided fundamental knowledge on the fate of particulate systems in vivo and how this fate can be manipulated for therapeutic gain. 

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