Targeting passive

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]. 

Doxil , of which I had the pleasure of being one of the inventors (1-12), serves as an example of successful passive targeting to tumors in animals and humans (1,3,4,13). The ammonium sulfate (AS) transmembrane inside high/outside low gradient-driven loading is also the basis for doxorubicin (DOX) loading for Targeted Doxil (14), which soon will be tested in clinical trials. 

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... 

We have shown that polymeric micelles constmcted of block copolymers of poly(ethylene oxide) (PEG) and poly(L-asparate) containing the anticancer dmg (adriamycin, ADR) selectively accumulate at solid tumor sites by a passive targeting mechanism. This is likely due to the hydrophilicity of the outer PEG chains and micellar size (<100 nm) that allow selective tissue interactions [17,18]. Polymeric micelle size ranges are tailored during polymer synthesis steps. Carefully selection of block polymer chemistry and block lengths can produce micelles that inhibit nonselective scavenging by the reticuloendothelial system (RES) and can be utilized as targetable dmg... 

Therefore, DCM-Dex/CDDP conjugates with passive targeting ability to tumor can be expected to alleviate severe renal toxicity CDDP in the clinical cancer therapy. 

Polymeric micelles are mostly small (10-100 nm) in size and dmgs can be incorporated by chemical conjugation or physical entrapment. For efficient delivery activity, they shonld maintain their integrity for a sufficient amount of time after injection into the body. Most of the experience with polymeric micelles has been obtained in the field of passive targeting of anticancer drugs to tumours [33]. Attachment of antibodies or sugars, or introduction of a polymer sensitive to variation in temperature or pH has also been stndied [32]. 

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... 

Yokoyama, M. 1998. Novel passive targetable drug delivery with polymeric micellSotelated Polymers and Gels, T. Okano Ed., Academic Press, San Diego, pp. 193-229. 

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... 

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