Liposomes passive targeting

Table 1 Requirements to Achieve Therapeutically Efficacious Passive Targeting of Liposomes Loaded with Drugs and Their Solution...

Main requirements to achieve therapeutically efficacious passive targeting of liposomes... 

In addition to the passive targeting of tumors due to the EPR effect, active targeting of PEGylated liposomes has also been successful. A study by Huwyler and coworkers (1996), for example, showed that coupling a monoclonal antibody to the surface of PEGylated liposomes resulted in significant transfer of the liposomes across the blood-brain barrier, which is difficult to achieve otherwise. The attached... 

Unfortunately, unmodified liposomes are rapidly coated with globular apoproteins found in serum. This is also true of injectable lipid emulsions but here this reaction is desirable since the oils are administered for nutritional purposes and it is an advantage for them to be rapidly metabolized. In the case of liposomes, passive destruction by the lymphoreticular endothelial system (LRES) is not necessarily desirable, especially if the system is targeted to a specific surface such as a tumor which may be remote from the injection site. 

Conventional liposomes, which are neutral or negatively charged, are generally used for passive targeting to the cells of the MPS. 

Conventional liposomes are those that do not carry any sterically stabilizing or targeting moieties on their surface. Their biodistribution depends strongly on their physicochemical properties (size, potential, composition) and physiological and pathological conditions of the body [193], Thus, conventional liposomes comprise the passive targeting of drug molecules. 

However, the administration of free doxorubicin often leads to dose-limiting side effects such as cardiotoxicity and myelosu-pression. This toxicity can be reduced by liposomal encapsulation of doxorubicin because of the modified biodistribution of the drug (1). Additionally, the efficiency of the drug is improved due to the passive targeting effect of liposomes. 

Decreased lymphatic drainage keeps the carriers in the tumor. This passive targeting mechanism has been called the enhanced permeation and retention (EPR) effect and was first identified by Maeda et al. [98,99]. Numerous studies have shown that the EPR effect results in passive accumulation of macromolecules and nanosized particulates (e.g., polymer conjugates, polymeric micelles, dendrimers, and liposomes) in solid tumor tissues, increasing the therapeutic index while decreasing side effects. Figure 4 describes the concept of passive tumor targeting by EPR effects. 

As early as 1981, researchers were making multilamellar liposomes entrapping diatrizoic add salts (Renografin) and passively targeting the spleen, one of the natural end points of such unPEGylated liposomes. Although they may initiate nonspecific macrophage activation, these systems have the... 

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