Antibody-directed liposomes as drug-delivery vehicles

Abstract

The field of liposome targeting has developed rapidly in the past 10 years as a multidisciplinary approach to the controlled delivery of bioactive molecules. Liposomes as delivery vehicles offer several benefits over the administration of free compounds as therapeutic devices. Advantages such as the ability to encapsulate a wide variety of polar, nonpolar, and amphipathic agents make the liposome an attractive delivery device for many applications. Encapsulation protects the drug from metabolic degradation and protects host tissue from non-specific effects until their arrival at the site of consumption. The large relative carrying capacity of the liposomes permits the transfer of thousands of drug molecules to a given cell. Regardless of the type of liposome or its route of administration, the primary consumer of either empty or drug-laden liposomes are the highly phagocytic members of the reticuloendothelial system. Thus, except for these ‘natural’ target cells, liposomes remain relatively non-specific transporters. Conjugation of targeting ligands such as antibodies to the drug or drug carrier confers specificity of that complex for a certain cell or organ expressing the targeted antigenic determinant. However, direct conjugation of drug with antibody has met with limited success, due in part to the required chemical coupling between the drug and antibody. Alternatively, by first entrapping a native drug into a liposome by a non-perturbing method, followed by conjugation of antibodies to the surface of the liposome, some of the advantages of either independent approach may be realized without many of the disadvantages. The pros and cons of this general approach have been debated during the past decade in many comprehensive reviews and monographs that have been published on the subject of liposome targeting. The primary emphasis of the current effort is to focus on one particular strategy for liposome targeting, i.e., the use of antibodies as vector molecules for targeted liposome drug delivery systems. In the sections that follow we try to describe the progress realized and the pitfalls and the limitations encountered with this approach to drug targeting.