Enhanced permeability and retention effect

A number of studies have examined the use of a dendrimer drug carrier to treat a variety of tumors. One approach has been based on the exploitation of the enhanced permeability and retention effect (EPR effect) to localize drug conjugates in tumor tissue. " A second approach has involved the conjugation of a... 

Minko T, Kopeckova P, Pozharov V, Jensen K, Kopecek J. The influence of cytotoxicity of macromolecules and of VEFG gene modulated vascular permeability on the enhanced permeability and retention effect in resistant solid tumor. Pharm Res 2000 17 505-514. 

The passive targeting of polymeric micelles to solid tumors can be achieved by the enhanced permeability and retention effect (EPR effect). Maeda and his coworkers presented this new drug targeting strategy in 1986 (31,32). As illustrated in Fig. 3, the vascular permeability of tumor tissues is enhanced by the actions of secreted factors such as kinin. As a result of this increased vascular permeability, macromolecules selectively increase their transport from blood vessels to tumor tissues. Furthermore, the lymphatic drainage system does not operate effectively in tumor tissues. 

Tumor-Targeted Macromolecular Drug Delivery Based on the Enhanced Permeability and Retention Effect in Solid Tumor... 

Table 1 Factors affecting enhanced permeability and retention effect that influence the accumulation of macromolecular drugs in solid tumors...

Passive accumulation and physiological effects have been exploited for disease treatment in preclinical models for inflammation and cancer ° without surface modification or active targeting by ligand attachment. This may reflect the neovasculature associated with these conditions and the enhanced permeability and retention effect in tumors in which nanoscale particles migrate and accumulate across leaky vasculature in disease tissue. Relying on physiological conditions, however, limits the capability to control the location and dose and results in widespread biodistrihution commonly associated with unmodified nanoparticles that... 

A. K. Iyer et al.. Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov. Today, 11(17-18), 812-818 (2006). 

Dendritic polymers may also have application in the delivery of anticancer agents. Dendrimers have been shown to selectively deliver a high payload of traditional chemotherapeutic agents, such as cisplatin, to a tumor [305]. Blood vessels in tumors have a higher permeability and poorer lymphatic drainage than vessels in normal tissue. This enhanced permeability and retention effects (EPR effect) allows selective delivery of a dmg to a tumor, and has been demonstrated with nondendritic polymer-antitumor agent conjugates [306,307]. 

In the same model of subcutaneous glioma, there has been recent work to inject, this time intravenously, LNC loaded with ferrocidiphenol 15 and coated with long PEG chains. The coating of the nanocapsules allows the LNC to remain longer in the bloodstream than conventional LNC, and thus to enhance accumulation in tumors through the EPR (enhanced permeability and retention) effect. Indeed, tumoral progression curves show a marked reduction in the size of tumors in treated rats. After several days, the tumor volume diminishes significantly to the point of disappearance at the end of the experimental period [156]. 

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