Tel Aviv University (TAU)- Research Group
Prof. Rimona Margalit
Affiliation Department of Biochemistry and Molecular Biology The George S. Wise Faculty of Life Sciences Tel Aviv University
Prof. Rimona Margalit
Office phone: 972-3-6409822
Lab phone: 972-3-6409822
Office fax: 972-3-6406834
The George S.Wise faculty of life sciences
Department of Biochemistry and Molecular Biology
Tel Aviv University
Tel Aviv 69978, Israel
Our efforts in the drug delivery arena focus on three drug delivery technologies that are inventions of our group. All are based on biomaterials, and can form vesicular-shaped particles, and have active in vivo targeting abilities. A wide scope of drugs and probe molecules can be encapsulated inside these carriers, encompassing small and large molecules, hydrophilic and hydrophobic. More than one drug/probe can be encapsulated in the same carriers. Additional targeting moieties can, furthermore, be attached to the surface of the carriers. All three carrier types have a high safety profile.
The particles of one technology are named Bioadhesive Liposomes (BALs), consisting of regular liposomes, that can made as nano- or as micro- particles. The liposomal shell is a lipid bilayer membrane that is surface-modification by covalent binding of target-recognition agents such as hyaluronan, collagen, EGF or gelatin to the liposomal surface.
The particles of the second technology are named gagomers (GAGs), their shell is made of hyaluronan, and their interior contains lipid clusters and water. Gags can also be made as nano- or micro-particles.
The particles of the third technology can only be made as microprticles, they are named collagomers, their shell is made of collagen and their interior from collagen-lipid conjugates, with nooks and crannies that can accommodate drugs and water.
The goal is to apply these particles as drug carriers for the treatment of pathologies such as tumors, infectious diseases, diabetes and inflammatory diseases, in order to improve deficiencies of treatment with free drugs, as the latter lead to poor therapeutic responses and to treatment failures. The choice of more than one carrier technology allows for the match of carrier species, size and route of administration that best-fits the designated therapy. Our conceptual approach, for any project, is to start at the molecular level and proceed systematically to studies in cell cultures, and then to animal studies. At the molecular level we investigate structural, physicochemical and biochemical properties of the drug-carrier systems selected for a given task. In cell cultures we explore cell–carrier interactions with particular emphasis on: kinetics and thermodynamics of cell-carrier binding, cellular localizations of carrier and drug, the mechanisms by which carrier-mediation affects drug entry into cells, and therapeutic activity. The in vivo studies in animal's models bearing the given pathology focus on pharmacokinetics, drug and carrier biodistributions, adverse effects, and therapeutic responses.
Drug delivery to tumor cells mediated by targeted nano carriers. Left-hand side: Bioadhesive Liposomes bound to mouse melanoma cells. Drug load (fluorescein, green fluorescence) is localized at the cell membrane. Right-hand side: Gagomers (red fluorescence) bound to mouse leukemia cells. Drug load (doxorubicin, red fluorescence) is localized inside the cell.
Margalit R (2012) Biomaterial-Based Particulate Drug Carriers. In Handbook of Harnessing Biomaterials in Nanomedicine. Peer D. Ed. Pan Stanford Publishing Pte. Ltd. Singapore. Chapter 1, pp. 1-16
Yifat Glucksam-Galnoy Y, Tsaffrir Z, Margalit R (2012) Hyaluronan-modified and regular multilamellar liposomes provide sub-cellular targeting to macrophages, without eliciting a pro-inflammatory response. J Cont. Rel. 160, 388–393
Margalit R, Yerushalmi N, Peer D, Rivkin I (2012) Formulations of water insoluble or poorly water soluble drugs in lipidated glycosaminoglycan particles and their use for diagnostic and therapy. US patent # 8,178,129
Rivkin I, Cohen K, Koffler J, Melikhov D, Peer D, Margalit R (2010) Paclitaxel-clusters coated with hyaluronan as selective tumor-targeted nanovectors. Biomaterials 31, 7106-7111.
Dekel Y, Glucksam Y, Margalit R (2010) Novel fibrillar insulin formulations for oral administration: Formulation and in vivo studies in diabetic mice. J. Cont. Rel. 143, 128-135.
Elron-Gross I, Glucksam Y, Margalit R (2009) Liposomal dexamethasone-diclofenac combinations for local Osteoarthritis treatment. Intl. J. Pharma. 376, 84-91.
Margalit R, Peer D (2009) Lipidated glycosaminoglycan particles and their use in drug and gene delivery for diagnosis and therapy. US patent # 7,544,374.
Barkay Z, Rivkin I, Margalit R (2009) Three-dimensional characterization of drug-encapsulating particles using STEM detector in FEG-SEM. Micron 40, 480-485.
Elron-Gross I, Glucksam Y, Biton IE, Margalit R (2009) A novel Diclofenac-carrier for local treatment of Osteoarthritis applying live-animal MRI. J. Cont. Rel. 135, 65-70.
Glucksam Y, Elron-Gross I, Raskin A, Gombein P, Keller N, Margalit R, Schumacher I. (2008). Control and prevention of bacterial infections in burns by new formulations based on drug/carrier systems. J Israeli Military Med, 5, 66-70.
Elron-Gross I, Glucksam Y, Melikhov D, Margalit R (2008) Cyclooxygenase inhibition by diclofenac formulated in bioadhesive carriers. Biochim. Biophys Acta.1778, 931-936.
Tel Aviv University (TAU)
Ben-Gurion University of the Negev (BGU)
The Hebrew University of Jerusalem (HUJI)
Bar-Ilan University (BIU)