טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentGabay Martin
SubjectTreatment Of Brain Tumors Utilizing Liposome-Based Targeted
Drug-Delivery System
DepartmentDepartment of Medicine
Supervisors PROFESSOR EMERITUS Moshe Gavish
PROF. Yeshayahu(Sha Katz
Full Thesis textFull thesis text - English Version


Abstract

Brain tumors as well as other brain disorders, such as Parkinson’s, Alzheimer’s and Huntington diseases are virtually hard to treat with the currently available therapy. 1,2 The major obstacle in the treatment of brain diseases is the lack of therapeutic strategies capable to penetrate the blood brain barrier (BBB). The BBB is an endothelial interface that separates the brain from the circulatory blood system and prevents the exposure of the Central Nervous System (CNS) to circulating toxins and potentially harmful compounds. At the same time, the BBB prevents the penetration of therapeutic compounds into the brain.

We present here a drug-delivery liposomal carrier, conjugated to a peptide inserted in the liposomal membrane, which is recognized by BBB transporters. The peptide is a short sequence of 6 amino acids (HRERMS) present in the amyloid precursor protein (APP). This APP-targeted liposomal system was designed specifically for transporting compounds with anti-cancer activity via the BBB in an effective manner. This drug-delivery liposomal carrier loaded with the anti-cancer compounds temozolomide

(TMZ), curcumin and doxorubicin crossed the BBB in an in vitro model as well as in mice. In an in vitro model of the BBB targeted-liposomes crossed the BBB 4-fold higher than the non-targeted liposomes. PE-cy-7-labeled targeted liposomes penetrated the brain in vivo 35% more than non-targeted liposomes. Treatment of the liposomes loaded with the anti-cancer agents, delayed the tumor growth and prolonged the mice survival in a range of 45% -70%. Dues it appears that the targeted liposomal drug-delivery system enables better efficacy of the treatment of a mouse model of glioblastoma compared to the corresponding free compounds.