Liposomes blood-brain barrier

One possibility to enhance, in a controlled manner, entry of drugs into the CNS would be to alter P-glycoprotein function at the blood-brain barrier. Such an enhancement could result from (1) direct modification of export pump function by inhibitors and intracellular signals or (2) bypassing the export pump by delivery systems not being recognized as substrates (e.g., nanoparticles or vector-coupled liposomes, which are taken up by endocytotic mechanisms) [58-65],... 

Plasma clearance (Cl), blood-brain barrier permeability surface area product (PS) and accumulation as % injected dose detected in brain tissue (%ID tissue) at 1 h after administration. Results show free [ H]-daunomycin (Daunomycin), [ H]-daunomycin encapsulated in conventional liposomes (Liposomes), sterically stabilized liposomes (PEG-liposomes), immunoliposomes (29 0X26, where 29 designates the number of 0X26 mAb conjugated per liposome) and control immunoliposomes where the 0X26 mAb was replaced by a non-specific isotype control antibody (IgG2a). Values are means SEM of n = 3 experiments. 

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... 

Intravenous Administration Liposomes administered intravenously face barriers such as the endothelial lining of the vasculature and the blood-brain barrier. Extravasation of the liposomes occurs only in organs such as liver, spleen, and bone... 

Xie, Y., Ye, L., Zhang, X., Cui, W., Lou, J., Nagai, T., and Hou, X. (2005), Transport of nerve growth factor encapsulated into liposomes across the blood-brain barrier In vitro and in vivo studies, / Controlled Release, 105,106-119. 

Rg = H or CH, Rg = Et, R4 = Ph), which have pifa in the range of 7-8 and are 40-60% dissociated, are capable of crossing the blood-brain barrier and exertingCNS effeets, including sedation. It was shown that the ionized form of barbiturates can permeate liposomal bilayers provided that 5-substituents impart sufficient lipophilicity (157). 

FIGURE 22.1 Breaches in the blood-brain barrier (BBB). In various CNS diseases, the BBB becomes leaky to macromolecules, and in CNS injuries, destruction of the endothelial lining creates permeability. By taking advantage of these characteristics, extravasation by nanoparticles, that is, liposomes, dendrimers, polymer-based diagnostics systems, can reach deep within the CNS. Figure adapted from Ref. [34]. 

The use of liposomes for the transfer of therapeutic enzymes through the "blood-brain" barrier, which permits to deliver these enzymes into cells of the central nervous system also seems very attractive. It has been already shown that horse raddish peroxidase, encapsulated into liposomes made of phosphatidylcholine, cholesterol and phosphatidic acid (7 2 1 molar ratio), acquires the ability to cross the hemato-encephalic barrier, whereas the native enzyme cannot. The presence of peroxidase in brain cells was proved by histochemical methods. The same authors have shown that after injection of the liposomal glucose oxidase into the rat s tail vein, up to 5% of the enzymatic activity can be discovered in brain tissues. ... 

Whereas the relationship of solute permeability with lipophilicity has been studied in a large number of in vivo systems (including intestinal absorption models [54,55], blood-brain [56 58] and blood nerve [59] barrier models, and cell culture models [60 62], to name just a few), numerous in vitro model systems have been developed to overcome the complexity of working with biological membranes [63-66]. Apart from oil-water systems that are discussed here, the distribution of a solute between a water phase and liposomes is... 

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