Enhanced permeability and

In cancer treatment, passive targeting of macromolecular carriers to tumors is a commonly used approach. This passive targeting is based on the enhanced permeability and retention (EPR) effect, which leads to an accumulation of the high molecular weight carrier in the tumor tissue. The EPR effect arises from the different physiology of tumor vasculature, where the vessel walls are highly porous and lack the tight junctions that are present in healthy tissue. As a result, macromolecular carriers extravasate and accumulate preferentially in tumor tissue relative to normal tissues [63, 64]. 

Shielded polyplexes with improved blood circulating properties are interesting tools for systemic cancer therapy (see Sect. 4.2). Nanoparticles can take advantage of the enhanced permeability and retention (EPR effect) [89] for passive tumor targeting. The EPR effect is based on the leakiness of tumor vasculature, due to neovascularization in growing tumors, combined with an inadequate lymphatic drainage. Nanoparticles with an elongated plasma circulation time can extravasate and passively accumulate at the tumor site. 

Maeda H (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41 189-207... 

Nanosized objects perform various functions in the biomedical field. In the human body, nanosized particulate substances behave very differently from larger particles. In 1986, Maeda et al. found that the stained albumin, having a size of several nanometers, naturally accumulates in the region of cancerous tissues, which is now well known as the enhanced permeability and retention (EPR) effect. Many studies in the field of nanoparticles are based on this finding. Another application of nanoparticles is the delivery system using various polyplexes that are composed of carrier molecules and plasmid DNA or nucleic acid drugs such as antisenses and siRNA. In addition, nanofibers are mainly used for biodegradable scaffolds in tissue... 

Abbreviations PDT, Photodynamic therapy EPR, Enhanced permeability and retention IHF, Tetrahydrofuran UV, Ultraviolet DNA, Deoxyribonucleic acid PL, Photoluminescence SWNT, Single-walled nanotube DWNT, Double-walled nanotube MWNT, Multi-walled nanotube IV, Intravenous HSP, Heat shock protein ... 

The strategy for nanosized (<--200 nm) polyplexes to reach the tumor site after systemic in vivo delivery called passive targeting takes advantage of the enhanced permeability and retention (EPR) effect [17]. This phenomenon implies... 

Thermally induced permeability enhancement of the more lipophilic solutes (butanol, octanol and hydrocortisone) through hairless mouse stratum corneum occurred in the temperature range also associated with lipid transitions in the calorimetry studies. Therefore, it seems likely enhanced permeabilities and lipid mobility within the stratum corneum are correlated. However, these macroscopic studies are unable to provide more specific information concerning the molecular origins of the thermal transitions. The studies provide even less information concerning possible irreversible alterations of the keratinized protein components of the stratum corneum. 

A further consideration is that under pathological conditions, endothelium exhibits modified characteristics. In general, the permeability is enhanced this phenomenon is called the enhanced permeability and retention (EPR) effect. For example, the endothelial fenestrations in inflammation sites can be as large as 0.2 pm. Also, in tumor tissue, even larger fenestrations can be found. However, in this case, the pattern is not uniform and depends on the tumor type and stage of development. Even within one... 

The size of the polyplex is also crucial to its function. The threshold for first-pass elimination by the kidneys is approximately lOnm in diameter defining a rough lower size limit for nanoparticles (21). Upper size limits are more difficult to establish as they depend on a variety of factors that are variable within tumors including penetration of capillary endothelium, diffusion rates in tumor interstitium and intracellular spaces (22). Macromolecular complexes preferentially accumulate in tumors through the enhanced permeability and retention (EPR) effect (23). Ideally, a nanoparticle would be in a size window such that it could take advantage of the EPR effect. The size of the polyplex can be readily modified during complexation by altering the DNA to polymer ratio (24). 

Greish, K. (2007) Enhanced permeability and retention of macromolecular drags in solid tumors a royal gate for targeted anticancer nanomedicines. Journal of Drug Targeting 15 457-464. 

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