Prof. Rimona Margalit

ביוכימיה וביולוגיה מולקו אמריטוס
Prof. Rimona Margalit
Phone: 03-6409822
Fax: 03-6406834
Office: Sherman - Life Sciences, 603A

Research Interests

1. Micro- and nano-particulate drug delivery technologies for topical, regional and systemic applications:  Our efforts in the drug delivery arena focus on two drug delivery technologies, one veteran and one novel, that are inventions of our group. These technologies each yield, micro and nano sized particles that are composed of biomaterials with particular emphasis on naturally occurring adhesion macromolecules as integral components for drug delivery and targeting. The two technologies we developed have the potential to resolve limitations of the other carriers. The veteran technology is named Bioadhesive Liposomes (BAL). These are drug-encapsulating liposomes that have been surface-modified by covalent binding of target-recognition agents such as hyaluronan, collagen, EGF or gelatin to their surface. Developed originally for local (topical and regional) drug therapies, recent studies have shown that nano (unilamellar) hyaluronan-liposomes are also suitable for therapies that require systemic administration. The novel technology (currently in the process of patenting), while also belonging to the particulate class of drug carriers, is an entirely new conceptual approach; it is different from liposomes and other lipid-based particles, as well as from nanospheres and microspheres, be they from biological or synthetic materials. It has a wide scope of therapeutic applications, and is suitable for both local and systemic applications. These novel carriers are, furthermore, non toxic. In all cases tested, and for both carrier technologies, the therapeutic outcomes with carrier-mediated therapy are significantly increased as compared to free drugs.

 

Current projects with the novel technology include:

  • Structural characterization, in particular size, shape, surface properties and mapping of internal domains.
  • Formulation studies of large and small drugs, hydrophilic and hydrophobic.
  • In vitro and in vivo studies in tumor chemotherapy, focusing on syngeneic and on nude mouse tumor models.
  • Gene transfection (in vitro and in vivo) and
  • Drug delivery for the treatment of neurodegenerative diseases, especially exploring (in vivo) BBB bypass approaches.

 

2. Novel chemosensitizers for overturning multidrug resistance (MDR) to tumor chemotherapy;  Chemotherapy frequently fails cancer patients due to inherent or acquired multidrug resistance (MDR). In the dominant mechanism, intracellular levels of cytotoxic drugs are reduced below their lethal thresholds due to active extrusion of the cytotoxic drug(s) from the tumor cell, operated by ATP-dependent pumps such as P-glycoprotein (Pgp), Multidrug Resistance-associated Protein (MRP), Lung Resistance-related Protein (LRP) and others. Reducing, or better yet, abolishing the extrusion, by pump inhibition, is a main approach to overturning MDR. The search for effective inhibitors (also named chemosensitizers, MDR modulators, MDR reversal agents) is now into the third generation.  Chemical derivatization of 1st-generation molecules and combinatorial chemistry lead to 2nd and 3rd generation chemosensitizers. These were more potent and less toxic than 1st-generation compounds, yet many were still prone to adverse effects, to unfavorable changes in plasma pharmacokinetics (PK) of the anticancer drugs, and to poor solubility. Few are currently in early clinical trials.

 

Current projects in the lab include:

  • Extension of the in vivo studies with the identified molecule, to include a wide repertoire of anticancer drugs and tumor types.
  • Exploration of additional approved drugs from the same family of the identified one, for their potential in MDR reversal.
  • Studies on the mechanism(s) by which this new class of chemosensitizers modulates MDR.
  • Investigation of potential benefits from combinations of carrier-mediated chemotherapy and chemosensitizers.

 

For a more detailed research description.

 

Recent Publications

Margalit, R., Alon, R., Linenberg, M., Rubin, I., Roseman, T.J. and Wood, R.W. (1991) Liposomal drug delivery: thermodynamic and chemical kinetic considerations. J. Controlled Release 17, 285-296

 

Margalit R., Okon, M., Yerushalmi Y. and Avidor E., (1992) Bioadhesive liposomes for topical drug delivery: Molecular and cellular studies. J. Controlled Release 19, 275-288

 

Yerushalmi N. and Margalit R. (1994) Bioadhesive collagen-modified liposomes: Molecular and cellular le vel studies on the kinetics of drug release and on binding to cell monolayers. Biochim. Biophys. Acta 1189, 13-20.

 

Yerushalmi N., Arad A. and Margalit R. (1994) Molecular and cellular studies of hyaluronic-acid modified liposomes as bioadhesive carriers of growth factors, for topical delivery in wound healing. Arch. Biochem. Biophys. 313, 267- 273

 

Lichtenstein A. and Margalit R. (1995) Liposome-encapsulated SSD for the topical treatment of infected burns: Thermodynamics of drug encapsulation and kinetics of drug release. J. Inorg. Biochem. 60, 185-197

 

Margalit R. (1995) Liposome-mediated drug targeting in topical and regional therapies. Critical Rev. Therap. Drug Carrier Sys. 12, 233-261

 

Margalit R. and Yerushalmi N. (1996) Liposomes as pharmaceutical products. In: "Microencapsulation Methods and Industrial Applications”, S. Benita, ed., Marcel Dekker Inc., Chapter 10, pp. 59-295

 

Margalit, R. (1996) Bioadhesive liposomes in topical treatment of wounds. In: “Microparticulates- Preparation, Characterization and Application in Medicine”, S. Cohen and H. Berenstein, eds., Marcel Dekker Inc., Chapter 15, pp. 425-461

 

Schumacher, I. and Margalit, R. (1997) Liposome-encapsulated Ampicillin: physicochemical and antibacterial properties. J. Pharm. Sci.86, 635-641

 

Yerushalmi, N. and Margalit, R. (1998) Hyaluronic-acid modified bioadhesive liposomes as local drug depots: effects of cellular and fluid dynamics on liposome retention at target sites. Arch. Biochem. Biophys. 349, 21-26

 

Schumacher, I., Arad, A. R. and Margalit R. (1999) Butyrylcholinesterase formulated in liposomes. Biotechnol. Appl. Biochem. 30, 225-230

 

Peer, D. and Margalit, R. (2000) Physicochemical evaluation of a stability-driven approach to drug entrapment in regular and in surface-modified liposomes. Arch. Biochem. Biophys. 383, 185-190

 

Peer, D., Florentin, A. and Margalit, R. (2003) Hyaluronan is a key component in cryoprotection and formulation of targeted unilamellar liposomes. Biochim. Biophys. Acta 1612, 76-82

 

Peer D, and Margalit R (2004). Loading Mitomycin C inside long circulating hyaluronan targeted nano-liposomes increases its antitumor activity in three mice tumor models. Inter. J. Cancer, 108, 780-789.

 

 

Patents

R. Margalit. Binding of recognizing substances to liposomes. Australia (#651414) 1994

R. Margalit. Binding of growth hormones to liposomes. Australia (#649796) 1995

R. Margalit. Binding of growth hormones to liposomes. Europe (#EPO525163) 1995

R. Margalit. Binding of recognizing substances to liposomes. Europe (#EPO525132), 1995

R. Margalit. Binding of protein and non-protein recognizing substances to liposomes. US (# 5401511),1995

R. Margalit. Sustained drug release through topical application of bioadhesive liposomes. Europe (#EPO525167), 1995

R. Margalit, T.J. Roseman, and R.W. Wood. Interaction between bioadhesive liposomes and target sites. Australia, (#656173), 1995.

R. Margalit. Method of binding recognizing substances to liposomes. US (# 5603872), 1997

R. Margalit (1998) Method of binding collagen recognizing substances to liposomes US (# 5846561)

R. Margalit, Inventor (2000), in the field of liposomes and proteins, submitted US

R. Margalit and I. Gonda, Inventors (2000), in the field of liposomes and gene therapy, submitted, US

D. Peer and R. Margalit (2001). In the field of biomaterials and drug delivery, submitted, U.A and PCT.

D. Peer and R. Margalit (2001). Method and pharmaceutical composition for the treatment of cancer, submitted US CIP and PCT.

D. Peer and R. Margalit (2002). Methods, pharmaceutical compositions and pharmaceutical kits for enhancing the therapeutic efficiency of cancer chemotherapeutic agents. Submitted, US.

D. Peer and R. Margalit (2003) In the field of biomaterials and drug delivery. Submitted, U.S.

D. Peer and R. Margalit. Method and pharmaceutical composition for the treatment of cancer, US (#6630454B2), 2003

 

Tel Aviv University, P.O. Box 39040, Tel Aviv 6997801, Israel
UI/UX Basch_Interactive