Drug and gene targeting to the brain via blood–brain barrier receptor-mediated transport systems

Abstract The delivery of recombinant proteins, peptides, antisense agents, and non-viral gene medicines to brain via a trans-vascular route following intravenous administration is possible with the development of blood–brain barrier drug targeting technology. Drugs or genes are re-formulated and attached to molecular Trojan horses that ferry the drug or gene into brain via receptor-mediated transport across the BBB on endogenous peptide transport systems.

[1]  W. Pardridge,et al.  Imaging endogenous gene expression in brain cancer in vivo with 111In-peptide nucleic acid antisense radiopharmaceuticals and brain drug-targeting technology. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[2]  H. Vinters,et al.  Pharmacokinetics and Brain Uptake of Biotinylated Basic Fibroblast Growth Factor Conjugated to a Blood-Brain Barrier Drug Delivery System , 2002, Journal of drug targeting.

[3]  O. Rorstad,et al.  Characterization of the relaxant effects of vasoactive intestinal peptide (VIP) and PHI on isolated brain arteries , 1984, Brain Research.

[4]  W. Pardridge,et al.  Vector-mediated delivery of a polyamide ("peptide") nucleic acid analogue through the blood-brain barrier in vivo. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Busto,et al.  Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats , 1996, Brain Research.

[6]  W. Pardridge,et al.  Drug and gene targeting to the brain with molecular trojan horses , 2002, Nature Reviews Drug Discovery.

[7]  W. Pardridge,et al.  Carboxyl-directed Pegylation of Brain-derived Neurotrophic Factor Markedly Reduces Systemic Clearance with Minimal Loss of Biologic Activity , 1997, Pharmaceutical Research.

[8]  F. Calon,et al.  Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism. , 2003, Human gene therapy.

[9]  W. Pardridge,et al.  Intravenous RNA Interference Gene Therapy Targeting the Human Epidermal Growth Factor Receptor Prolongs Survival in Intracranial Brain Cancer , 2004, Clinical Cancer Research.

[10]  H. Vinters,et al.  Enhanced neuroprotective effects of basic fibroblast growth factor in regional brain ischemia after conjugation to a blood-brain barrier delivery vector. , 2002, The Journal of pharmacology and experimental therapeutics.

[11]  W. Pardridge,et al.  Conjugation of brain-derived neurotrophic factor to a blood–brain barrier drug targeting system enables neuroprotection in regional brain ischemia following intravenous injection of the neurotrophin , 2001, Brain Research.

[12]  W. Pardridge,et al.  Neuroprotection with noninvasive neurotrophin delivery to the brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  W. Pardridge,et al.  Epidermal growth factor radiopharmaceuticals: 111In chelation, conjugation to a blood-brain barrier delivery vector via a biotin-polyethylene linker, pharmacokinetics, and in vivo imaging of experimental brain tumors. , 1999, Bioconjugate chemistry.

[14]  X. Breakefield,et al.  Receptor Binding Activities of Biotinylated Derivatives of β‐Nerve Growth Factor , 1986 .

[15]  S. Yamada,et al.  Blood-Brain Barrier Transport of 125I-Labeled Basic Fibroblast Growth Factor , 2004, Pharmaceutical Research.

[16]  W. Pardridge,et al.  Central nervous system pharmacologic effect in conscious rats after intravenous injection of a biotinylated vasoactive intestinal peptide analog coupled to a blood-brain barrier drug delivery system. , 1996, The Journal of pharmacology and experimental therapeutics.

[17]  W. Pardridge,et al.  Neuroprotection in Transient Focal Brain Ischemia After Delayed Intravenous Administration of Brain-Derived Neurotrophic Factor Conjugated to a Blood-Brain Barrier Drug Targeting System , 2001, Stroke.

[18]  J. Mcculloch,et al.  Cerebral circulatory and metabolic effects of vasoactive intestinal polypeptide. , 1980, The American journal of physiology.

[19]  W. Pardridge,et al.  Normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism with intravenous nonviral gene therapy and a brain-specific promoter. , 2004, Human gene therapy.

[20]  W. Pardridge,et al.  Receptor‐mediated delivery of an antisense gene to human brain cancer cells , 2002, The journal of gene medicine.

[21]  W. Pardridge,et al.  Imaging brain tumors by targeting peptide radiopharmaceuticals through the blood-brain barrier. , 1999, Cancer research.

[22]  W. Pardridge.  Brain Drug Targeting: The Future of Brain Drug Development , 2001 .

[23]  Michael T. McManus,et al.  Gene silencing in mammals by small interfering RNAs , 2002, Nature Reviews Genetics.

[24]  C. Bucana,et al.  Differential permeability of the blood-brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice. , 1992, The American journal of pathology.

[25]  Jian Yi Li,et al.  Organ-specific gene expression in the rhesus monkey eye following intravenous non-viral gene transfer. , 2003, Molecular vision.

[26]  S. Finklestein,et al.  Delayed Treatment with Intravenous Basic Fibroblast Growth Factor Reduces Infarct Size following Permanent Focal Cerebral Ischemia in Rats , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.