Beyine İlaç Tașınması: Truva Atı Teknolojisi

Year 2014, Issue: 1, 1 - 16, 01.01.2014

Selin S. Doğan Seçil Toktaş Yılmaz Çapan

Abstract

Beyine İlaç Taşınmasında Kullanılan Taşıyıcı Sistemler, Ankara, 2013. KBE, beyni toksik ve zararlı bileşiklerden koruyarak homeostazı sağlayan, aynı zamanda pek çok etkin maddenin beyindeki hedef bölgelere ulaşmasını kısıtlayan en önemli faktördür. Tedaviyi sınırlayan bu fizyolojik bariyerin sebep olduğu engeli ortadan kaldırmak, ancak geliştirilen yeni stratejilerle mümkün olmaktadır. Nano boyutlu kolloidal sistemler, santral sinir sistemi hastalıklarının tedavisinde pasif ve aktif hedeflendirme yoluyla umut vaat eden yaklaşımlar olarak yer almaktadır. Bu yaklaşımlar arasında reseptör aracılı taşıyıcı RAT sistemler dikkat çekmektedir. Reseptörlere hedeflendirilmek üzere geliştirilen Truva Atı / Molecular Trojan Horse MTH teknolojisi sayesinde büyük moleküllü ilaçların beyine taşınmasına olanak sağlanmıştır. Hedeflendirilmiş taşıyıcı sistemlerin SSS’de kullanımları ile ilgili araştırmalar, günümüzde beyin kanseri, inme, Alzheimer, Parkinson, beyin travması gibi hastalıklar üzerinde yoğunlaşmaktadır. Bu çalışmanın amacı, kolloidal sistemlerin hedeflendirilmesinde kullanılan yaklaşımların ve güncel çalışmaların değerlendirilmesi ile yeni stratejilerin belirlenmesine olanak sağlamaktır.

Keywords

İlaç hedeflendirme, kan-beyin engeli, nanopartiküler sistemler, Truva atı

Beyine İlaç Tașınması: Truva Atı Teknolojisi

Abstract

Delivery Systems for Brain Drug Targeting, Ankara, 2013. Blood-brain barrier is the main factor which maintains homeostasis by protecting brain from toxic and harmful compounds, but it also represents the main limiting factor for a number of drug molecules to reach the aimed areas in brain. The only way to overcome this treatment-limiting obstacle could be reached by the help of new strategies. Nanoscale colloidal systems are promising strategies in the treatment of central nervous system CNS diseases by passive and active targeting. Receptor mediated transport systems RMT are in the spotlıght of targeting strategies.By the help of Molecular Trojan Technology, which is developed for receptor targeting, large molecule drugs will be transported to brain. Nowadays, research interest in targeted delivery systems in the treatment of CNS disorders has been focused on brain cancer, stroke, Alzheimer’s disease, Parkinson disease. Therefore, the aim of this present review is to evaluate the targeting approaches of colloidal systems and current studies for the development of new strategies.

Keywords

Drug targeting, blood-brain barrier, nanoparticulate systems, Trojan horse

References

• Beduneau, A., Saulnier, P.,Benoit, J.P. Active targeting of brain tumors using nanocarriers. Biomaterials, 28 (33), 4947-4967 (2007).
• Garcia-Garcia, E., Andrieux, K., Gil, S.,Couvreur, P. Colloidal carriers and blood-brain barrier (BBB) translocation: a way to deliver drugs to the brain? Int J Pharm, 298 (2), 274-292 (2005).
• Harikrishna Devalapally, A.C., Mansoor M. Amiji. Role of nanotechnology in pharmaceutical product development. Journal of Pharmaceutical Sciences, 96 (10), 2547-2565 (2007).
• Schnyder, A.,Huwyler, J. Drug transport to brain with targeted liposomes. NeuroRx, 2 (1), 99-107 (2005).
• VJ Mohanraj, Y.C. Nanoparticles – A Review. Tropical Journal of Pharmaceutical Research, 5 (1), 561-573 (2006).
• Newton, H.B. Advances in strategies to improve drug delivery to brain tumors. Expert Rev Neurother, 6 (10), 1495-1509 (2006).
• K. Ringe, C.M.W., B. A. Sabe. Nanoparticle Drug Delivery to the Brain. Encyclopedia of Nanoscience and Nanotechnology, 7, 91-104 (2004).
• Mittal, G., Carswell, H., Brett, R., Currie, S.,Kumar, M.N. Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer’s pathology. J Control Release (2010).
• Kreuter, J. Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev, 47 (1), 65-81 (2001).
• Pardridge, W.M. Molecular Trojan horses for blood-brain barrier drug delivery. Curr Opin Pharmacol, 6 (5), 494-500 (2006).
• Pardridge, W.M. The blood-brain barrier: bottleneck in brain drug development. NeuroRx: the journal of the American Society for Experimental NeuroTherapeutics, 2 (1), 3-14 (2005).
• Pardridge, W.M. Re-engineering biopharmaceuticals for delivery to brain with molecular Trojan horses. Bioconjug Chem, 19 (7), 1327-1338 (2008).
• Pardridge, W.M. Targeting neurotherapeutic agents through the blood-brain barrier. Arch Neurol, 59 (1), 35-40 (2002).
• Hwa Jeong Lee, B.E., Jayne Lesley, Ulrich Bickel, William M. Pardridge. Targeting Rat Anti- Mouse Transferrin Receptor Monoclonal Antibodies through Blood-Brain Barrier in Mouse. The journal of pharmacology and experimental therapeutics, 292 (3), 1048-1052 (2000).
• Pardridge, W.M. Blood-brain barrier delivery. Drug Discov Today, 12 (1-2), 54-61 (2007).
• Bickel, U., Yoshikawa, T.,Pardridge, W.M. Delivery of peptides and proteins through the blood-brain barrier. Adv Drug Deliv Rev, 46 (1-3), 247-279 (2001).
• Yesim Aktas, M.Y., Karine Andrieux, R. Neslihan Gursoy, Maria Jose Alonso,, Eduardo Fernandez-Megia, R.N.-C., Emilio Quinoa,Ricardo Riguera,, Mustafa F. Sargon, H.H.C., Ayhan S. Demir,A. Atilla Hıncal,Turgay Dalkara,,Yılmaz Capan, P.C. Development and Brain Delivery of Chitosan-PEG Nanoparticles Functionalized with the Monoclonal Antibody OX26. Bioconjugate Chemistry, 16, 1503-1511 (2005).
• Hulya Karatas, Y.A., Yasemin Gursoy-Ozdemir, Ebru Bodur, Muge Yemisci, Secil Caban, Atay Vural, Onur Pinarbasli, Y.C., Eduardo Fernandez-Megia, Ramon Novoa-Carballal, Ricardo Riguera, Karine Andrieux, P.C., Turgay Dalkara. A Nanomedicine Transports a Peptide Caspase-3 Inhibitor across the Blood–Brain Barrier and Provides Neuroprotection. The Journal of Neuroscience, 29 (44), 13761-13769 (2009).
• Pardridge, W.M. Blood–brain barrier delivery of protein and non-viral gene therapeutics with molecular Trojan horses. Journal of Controlled Release, 122, 345-348 (2007).
• Lee, H.J.,Pardridge, W.M. Pharmacokinetics and delivery of tat and tat-protein conjugates to tissues in vivo. Bioconjugate Chemistry, 12 (6), 995-999 (2001).
• Fujita, M., Lee, B.S., Khazenzon, N.M., Penichet, M.L., Wawrowsky, K.A., Patil, R. ve diğerleri. Brain tumor tandem targeting using a combination of monoclonal antibodies attached to biopoly(beta-L-malic acid). J Control Release, 122 (3), 356-363 (2007).
• Zhang, Y., Zhu, C.,Pardridge, W.M. Antisense gene therapy of brain cancer with an artificial virus gene delivery system. Mol Ther, 6 (1), 67-72 (2002).
• Zhang, Y., Zhang, Y.F., Bryant, J., Charles, A., Boado, R.J.,Pardridge, W.M. Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer. Clin Cancer Res, 10 (11), 3667-3677 (2004).
• Lee, H.J., Zhang, Y., Zhu, C., Duff, K.,Pardridge, W.M. Imaging brain amyloid of Alzheimer disease in vivo in transgenic mice with an Abeta peptide radiopharmaceutical. J Cereb Blood Flow Metab, 22 (2), 223-231 (2002).
• Sumbria, R.K., Boado, R.J.,Pardridge, W.M. Imaging Amyloid Plaque in Alzheimer’s Disease Brain with a Biotinylated Abeta Peptide Radiopharmaceutical Conjugated to an IgG-Avidin Fusion Protein. Bioconjugate Chemistry (2012).
• Saito, Y., Buciak, J., Yang, J.,Pardridge, W.M. Vector-mediated delivery of 125I-labeled beta-amyloid peptide A beta 1-40 through the blood-brain barrier and binding to Alzheimer disease amyloid of the A beta 1-40/vector complex. Proceedings of the National Academy of Sciences of the United States of America, 92 (22), 10227-10231 (1995).
• Xia, C.F., Zhang, Y., Boado, R.J.,Pardridge, W.M. Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology. Pharm Res, 24 (12), 2309-2316 (2007).
• Suzuki, T., Wu, D., Schlachetzki, F., Li, J.Y., Boado, R.J.,Pardridge, W.M. Imaging endogenous gene expression in brain cancer in vivo with 111In-peptide nucleic acid antisense radiopharmaceuticals and brain drug-targeting technology. J Nucl Med, 45 (10), 1766-1775 (2004).
• Zhang, Y.,Pardridge, W.M. 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. Brain research, 889 (1-2), 49-56 (2001).
• Song, B.W., Vinters, H.V., Wu, D.,Pardridge, W.M. Enhanced neuroprotective effects of basic fibroblast growth factor in regional brain ischemia after conjugation to a blood-brain barrier delivery vector. the journal of pharmacology and experimental therapeutics, 301 (2), 605-610 (2002).
• Fu, A., Hui, E.K., Lu, J.Z., Boado, R.J.,Pardridge, W.M. Neuroprotection in stroke in the mouse with intravenous erythropoietin-Trojan horse fusion protein. Brain Res, 1369, 203- 207 (2011).
• Zhou, Q.H., Hui, E.K., Lu, J.Z., Boado, R.J.,Pardridge, W.M. Brain penetrating IgG- erythropoietin fusion protein is neuroprotective following intravenous treatment in Parkinson’s disease in the mouse. Brain research, 1382, 315-320 (2011).
• Sumbria, R.K., Boado, R.J.,Pardridge, W.M. Brain protection from stroke with intravenous TNFalpha decoy receptor-Trojan horse fusion protein. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism, 32 (10), 1933-1938 (2012).