Delivery of Copper-chelating Trientine (TETA) to the central nervous system by surface modified liposomes
The existence of the blood-brain barrier (BBB) complicates the treatment of many central nervous system (CNS) disorders, including the copper storage disease, Wilson’s disease. Its CNS symptoms represent a serious problem, since therapeutics for Wilson’s disease do not cross the BBB. One strategy to...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
20 August 2016
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| In: |
International journal of pharmaceutics
Year: 2016, Jahrgang: 512, Heft: 1, Pages: 87-95 |
| ISSN: | 1873-3476 |
| DOI: | 10.1016/j.ijpharm.2016.08.040 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1016/j.ijpharm.2016.08.040 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0378517316307803 
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| Verfasserangaben: | Robin Tremmel, Philipp Uhl, Frieder Helm, Dominik Wupperfeld, Max Sauter, Walter Mier, Wolfgang Stremmel, Götz Hofhaus, Gert Fricker |
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| 520 | |a The existence of the blood-brain barrier (BBB) complicates the treatment of many central nervous system (CNS) disorders, including the copper storage disease, Wilson’s disease. Its CNS symptoms represent a serious problem, since therapeutics for Wilson’s disease do not cross the BBB. One strategy to overcome this obstacle is the transfer of drugs across the BBB with colloidal carrier systems like liposomes. The aim of the present study was to encapsulate triethylenetetramine (TETA), a copper chelating agent, into surface modified liposomes and to investigate their permeation across the BBB. Liposomes were modified with cationized bovine serum albumin or penetratin, a cell penetrating peptide. Liposomes were characterized regarding size, PDI, zeta potential and encapsulation efficiency. Size was between 139.4±1.9nm to 171.1±3.5nm with PDI’s below 0.2. Zeta potentials of vectorized liposomes were at least 6.9mV higher than those of standard liposomes. Cryo-TEM micrographs displayed liposomal structure, integrity and the similarity of structure and size between loaded, unloaded, vectorized and non- vectorized liposomes. In vivo experiments in rats showed an up to 16-fold higher brain uptake of TETA in vectorized liposomes compared to free TETA or TETA in non-vectorized liposomes, proving successful brain delivery using target seeking surface modifications. Tissue analysis indicated TETA concentrations in the brain being high enough to treat Wilson’s disease. | ||
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