Brain drug delivery and blood–Brain barrier transport

Pardridge, William M.

doi:10.3109/10717549309022762

Cited by 33 publications

(17 citation statements)

References 68 publications

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“…Examples of brain targeting vectors include cationized albumin, the OX26 monoclonal antibody to the rat transferrin receptor, or monoclonal antibodies to the insulin receptor. 14,15 Different types of coupling strategies have been developed to attach proteins to phospholipids or pegylated phospholipids while preserving their biological activity. Covalent coupling to phospholipids can be achieved using, for example, amino-reactive homobifunctional cross-linkers.…”

Section: Immunoliposomesmentioning

confidence: 99%

Drug transport to brain with targeted liposomes

2005

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Summary: Antibody-conjugated liposomes or immunoliposomes are particulate drug carriers that can be used to direct encapsulated drug molecules to diseased tissues or organs. The present review discusses examples of successful applications of this technology to achieve drug transport across the blood-brain barrier. In addition, information will be provided on practical aspects such as phospholipid compositions of liposomes, antibody coupling technologies, large-scale production of liposomes, and obstacles related to drug loading of the carrier. Prospects of future uses of immunoliposome-based drug delivery systems such as gene therapy of the brain and clinical trials are discussed.

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Section: Immunoliposomesmentioning

confidence: 99%

Drug transport to brain with targeted liposomes

2005

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“…The natural ligand of the receptor, ie, transferrin, can be coupled to the surface of pegylated liposomes to achieve tumor targeting (Ishida et al 2001). It is important to note, however, that the transferrin receptor (which has a binding constant K D of 5.6 nM) is heavily saturated in vivo by the µM endogenous plasma transferrin concentrations (Pardridge 1993). This strong competition with endogenous transferrin leads to poor in vivo receptor targeting after intravenous injection.…”

Section: Vector-conjugated Liposomesmentioning

confidence: 99%

Tumor targeting using liposomal antineoplastic drugs

Huwyler¹

2008

IJN

137

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During the last years, liposomes (microparticulate phospholipid vesicles) have been used with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumor drugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vectorconjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this fi eld of research.

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“…An explanation is provided by the observation that nanoparticles with a mean size around 170 nm, such as the OX7-IL, cannot penetrate across the endothelial layer in these tissues (Drummond et al 1999;Torchilin 2005). At least, the brain vasculature is characterized by a very tight capillary endothelium, the blood -brain barrier, which has an important protective function for this organ (Pardridge 1993). In the lungs, deposition of OX7-IL within the vasculature (but not the parenchyma) can be explained by endothelial cells expressing the Thy1.1 antigen (Danilov et al 2001).…”

Section: Discussionmentioning

confidence: 96%

Drug targeting using OX7-immunoliposomes: Correlation between Thy1.1 antigen expression and tissue distribution in the rat

Tuffin

Huwyler

Waelti

et al. 2008

Journal of Drug Targeting

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OX7 monoclonal antibody F (ab 0 )2 fragments directed against Thy1.1 antigen can be used for drug targeting by coupling to the surface of drug-loaded liposomes. Such OX7-conjugated immunoliposomes (OX7-IL) were used recently for drug delivery to rat glomerular mesangial cells, which are characterized by a high level of Thy1.1 antigen expression. In the present study, the relationship between OX7-IL tissue distribution and target Thy1.1 antigen localization in different organs in rat was investigated.Western blot and immunohistofluorescence analysis revealed a very high Thy1.1 expression in brain cortex and striatum, thymus and renal glomeruli. Moderate Thy1.1 levels were observed in the collecting ducts of kidney, lung tissue and spleen. Thy1.1 was not detected in liver and heart. There was a poor correlation between Thy1.1 expression levels and organ distribution of fluorescence-or 14 C-labeled OX7-IL. The highest overall organ density of OX7-IL was observed in the spleen, followed by lung, liver and kidney. Heart and brain remained negative. With respect to intra-organ distribution, a localized and distinct signal was observed in renal glomerular mesangial cells only. As a consequence, acute pharmacological (i.e. toxic) effects of doxorubicin-loaded OX7-IL were limited to renal glomeruli. The competition with unbound OX7 monoclonal antibody F (ab 0 )2 fragments demonstrated that the observed tissue distribution and acute pharmacological effects of OX7-IL were mediated specifically by the conjugated OX7 antibody. It is concluded that both the high target antigen density and the absence of endothelial barriers are needed to allow for tissue-specific accumulation and pharmacological effects of OX7-IL. The liposomal drug delivery strategy used is therefore specific toward renal glomeruli and can be expected to reduce the risk of unwanted side effects in other tissues.

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Brain drug delivery and blood–Brain barrier transport

Cited by 33 publications

References 68 publications

Drug transport to brain with targeted liposomes

Drug transport to brain with targeted liposomes

Tumor targeting using liposomal antineoplastic drugs

Drug targeting using OX7-immunoliposomes: Correlation between Thy1.1 antigen expression and tissue distribution in the rat

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