We develop a variety of vehicles and controlled-release systems to address the major obstacles in delivering therapeutics to treat cancer and HIV/AIDS. We were the first to reformulate PLGA particles to entrap unstable anti-angiogenic biologic (PEX) and synthetic (Gleevec) drugs, which were shown to reduce side effects and substantially improve the drugs’ efficacy in treating brain tumors. We also focused on designing unique and unorthodox nano-vesicle, as a targeted drug-delivery platform, to treat HIV/AIDS. These vesicles were produced from the intact cytoplasmatic membranes of non-human cells engineered to express the human receptor of a viral ligand found on HIV-infected cells. This system, which was shown to specifically target HIV-infect cells, does not entail the elaborate production of targeting molecules and their incorporation into the drug-delivery vehicle. Thus, the system represents a simpler and more clinically relevant approach than existing particulate delivery systems.
- O. Benny, S. Kim, K. Gvili, I.S. Radzishevsky, A. Mor, L. Verduzco, L.G. Menon, P.M. Black, M. Machluf,* and R.S. Carroll*. In vivo fate and therapeutic efficacy of PF-4/CTF microspheres in an orthotopic human glioblastoma model. FASEB, 22:1-12, 2008. * Corresponding authors. PUBMED
- O. Benny, L Manon, A. Gilert, E. Goren, P.M. Black, R.S. Carroll, and M. Machluf. Local delivery of PLGA microspheres containing imatinib mesylate inhibits intracranial xenograft glioma growth. Clinical Cancer Research, 15:1222-31, 2009. PUBMED
- T. Bronshtein, N. Toledano, D. Danino, S. Pollack, and M. Machluf. Cell derived liposomes expressing CCR5 as a new targeted drug-delivery system for HIV infected cells. Journal of Controlled Release, 151:139-48, 2011. PUBMED
The concept and rational of targeting HIV-infected cells by CCR5-conjuagted cell derived liposomes. (a) Cell-derived liposomes are prepared by homogenization and extrusion of ghost cells, which membranally express the HIV co-receptor CCR5. The source of the cells can be any autologous lineages that express CCR5 (naturally or exogenously). (b) Cell derived liposomes, which will be targeted against gp120-expressing cells using CCR5 as a targeting ligand, can interfere with all extracellular steps of viral pathogenesis; Such as, syncytium formation between infected cells and uninfected susceptible cells, viral budding from infected cells, viral maturation and attachment to susceptible cells. (c) The cell derived liposomes (when administered along with soluble CD4) are primarily intended to target, fuse with and deliver their cytotoxic content into gp120-expressing/HIV-infected cells. Accordingly, the same mechanism of gp120 binding may also prove efficient in preventing syncytium formation and inactivation of roaming virions by clustering.