Enhanced permeation and retention effect

By utilizing polymerization in the miniemulsion system, larger HPG analogues can be created by linking several HPG units to a nanoparticle in order to obtain an optimum diameter of 50 nm [116], This size range is considered to be ideal for drug delivery carriers that may accumulate in tumors or inflamed tissue by the enhanced permeation and retention effect (EPR) [52],... 

Passive Targeting Enhanced Permeation and Retention Effect... 

Figure 4.1 Left Tuning of renal clearance with bow-tie dendrimers built from 2,2-dimethylolpropionic acid. Right Enhanced permeation and retention effect on mediated tumour uptake [12]. Reproduced with permission from E.R. Gillies, E. Dy, J.M.J. Frechet and F.C. Szoka, Molecular Pharmaceutics, 2005,2, 2,129.

This is unfortunate because the theoretical advantage of nanosystems is their small size, allowing freer movement than microspheres in the circulation, including the lymph and in tissues. Flow rates are important not least in the determination of the possibility of nanoparticle interaction with endothelial receptors prior to internalization, or indeed in the decoupling of carriers and receptors due to shear forces. Flow of nanoparticles is a vital element in extravasation and in the enhanced permeation and retention (EPR) effect. What is the influence of nanoparticle size on particle flow in the circulation And, with the advent of CNTs in particular, what is the influence of shape on flow and fate CNTs certainly behave differently in the blood from spherical C60 fidlerenes. CNTs activate human platelets and induce them to aggregate, whereas their spherical analogues do not... 

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. 

Then it appeared that conjugation of drugs with a polymer or macromolecule enhanced its passive distribution in favour to tumour tissue. This enhanced permeation and retention (EPR) effect was explained by differences... 

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