Stealth effect

These are known by their registered tradename, Stealth liposomes (see Lasic 1993, p. 284). As discussed by Lasic, the stealth effect is the result of a steric layer surrounding the liposome, and these liposomes are also known as sterically stabilized liposomes. We discuss steric stabilization in Chapter 13. 

PLGA microspheres can be prepared in rather narrow size ranges from 0.2 /mi up to > 100 /mi. The preparation, properties and degradation of these polymers have been discussed extensively in Chapter 4 (see Section 4.5.1). PLGA microspheres can now be prepared with surface oriented PEG-chains which improves in vivo circulation time ( stealth-effects ). 

Gnanou, Taton et al. have reported a series of dendrimer-hke PEOs with an increasing structural complexity (Figure 27.7). In this case, the advantages of the dendritic stracture (multivalency and shape persistence) were combined with the specific properties of PEO, namely stealth effect, biocompatibihty, nontoxidty, low immunogenicity, and antigenicity. 

The present clinical data indicate that the pharmacokinetics of MCC-465 differ from those of the free doxombicin but are very similar to doxil in humans. Also, MCC-465 shows peak plasma levels and AUCs similar to the doxil. The increased AUCs result from the increased plasma levels. The volume of distribution at steady state (Vdss) ofMCC 65 is also similar to that reported for doxil (8). These pharmacokinetics data indicate that the stability in blood circulation of MCC-465 is similar to doxil. These results suggest that the conjugation of the F(ab )2 of GAH did not interfere with the stealth effect of the pegylated liposomes. Until now, we have not reached MTD yet. 

The advantageous effects of liposomal carrier systems include protection of compounds from metabolism or degradation, as well as enhanced cellular uptake. Liposome-mediated delivery of cytotoxic drugs to cells in culture has resulted in improved potency [58,59]. Prolonged release of encapsulated cargo has also been demonstrated [60,61]. More recently, liposomes with extended circulation half-lives and dose-independent pharmacokinetics (Stealth liposomes) [62] have shown promise in delivery of drugs that are normally very rapidly degraded. 

Zhu G, Oto E, Vaage J, et al. The effect of vincristine-polyanion complexes in STEALTH liposomes on pharmacokinetics, toxicity and anti tumor activity. Cancer Chemother Pharmacol 1996 39 138. 

MPEG-DSPE cholesterol— stealth liposomal pharmacology study, single- (transient effects in... 

Stealth liposomes Liposomal infusion reaction (hypoactivity, flushing, diarrhea, emesis, and decreased blood pressure seen following intravenous infusion in dogs) Transient effect (resolved within 1-2 hr). Biological significance is not apparent but the finding has been related to histamine release due to the infusion of a large amount of lipid 27... 

As described above, the circulation time of a particulate carrier in the blood can be prolonged using stealth technology to enhance particle hydrophilicity. If the circulation time is sufficiently prolonged and the particle size does not exceed, say, 0.2 urn, then accumulation at tumor and inflammation sites (EPR-effect) can be observed. 

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