Nano Technology for Better Antibiotics

Introduction

AMRazor (formerly Rebiotics Rx) develops nanotechnology-based antibiotics with the focus on resistant bacteria

The World Health Organization has classified antimicrobial resistance (AMR) as a leading global health threat. It is estimated that antibiotic-resistant bacteria currently cause the death of 700,000 people, and that by 2050 the number of deaths will reach 10 million, exceeding the predicted number of cancer death in that year and would cost the world up to USD 100 trillion. Furthermore, in the absence of effective treatments the success of major surgeries and cancer chemotherapies would also be compromised owing to bacterial contamination.

The introduction of novel antibiotics from the laboratory to the patient is a lengthy and expensive process. At AMRazor such development is significantly simplified, owing to the faster and much cheaper "way to market” combined with greater chances of success. We identify existing antibiotics whose usefulness is limited owing to their short lifetimes, their rapid degradation, or their neutralization by binding to plasma proteins. We have the ability to overcome these major deficiencies by employing suitable delivery systems. As a result, "old” antibiotics that are chemically available at a clinical grade, and have known modes of action and toxicity characteristics, can rapidly reach the stage of clinical trials and eventually gain approval for AMR treatment.

The technology

Nano-mupirocin, the lead product of AMRazor, is a PEGylated nano-liposomal formulation of the antibiotic mupirocin. Mupirocin, a topical cream antibiotic showing no cross-resistance with other antibiotics, is currently limited to topical application owing to its rapid degradation in the blood. Its encapsulation by a unique approach in PEGylated nano-liposomes (which resemble Doxil® liposomes in size and lipid composition) to form Nano-mupirocin enables mupirocin to become active by injection. Nano-mupirocin can therefore treat deep infections caused by resistant bacteria. It is active against pathogens defined as "urgent and serious threats” to public health, such as Neisseria gonorrhea, methicillin resistant Staphylococcus aureus (MRSA), Streptococcus pneumonia and Enterococcus faecium. Nano-mupirocin has demonstrated superior pharmacokinetics and efficacy in several animal models of infection.

Inventors

Professor Emeritus Yechezkel (Chezy) Barenholz

Prof. Barenholz heads the Liposome and Membrane Research Laboratory at the Hebrew University—Hadassah Medical School, Jerusalem, and is the Daniel G. Miller Professor in Cancer Research at the Hebrew University of Jerusalem. He has been a faculty member at Hebrew University since 1968 and a visiting professor at leading universities world-wide. His current research focuses on the development of drugs and nano-drugs, based on drug delivery systems best exemplified by the anticancer drug Doxil®, the first liposomal drug and nano-drug to be approved by the FDA (1995). Prof. Barenholz is the author of more than 430 scientific publications (cited more than 37,500 times, h-index >94), and is a co-inventor in more than 55 approved patent families. He is a founder of five start-up companies: Moebious, PolyPid, LipoCure, Ayana and RebioticsRx. He has received numerous national and international awards, including an Honorary Doctorate from the Technical University of Denmark (2012), the 2012 Founders Award of the Controlled Release Society, and the Israeli Prime Mininster’s 2020 Emet Prize for Excellence in Nanotechnology.

Professor Emeritus Amiram Goldblum

Prof. Goldblum is a principal investigator and a Professor Emeritus at the Hebrew University of Jerusalem. He heads the Molecular Modeling and Drug Discovery facility at the School of Pharmacy Institute for Drug Research. Prof. Goldblum received his Ph.D. in organic chemistry at the Hebrew University, and this was followed by postdoctoral studies in theoretical chemistry at CNRS Paris, Pomona College California, and Stanford University. In 1979 he joined the Medicinal Chemistry Department of the Hebrew University, where he developed and applied theoretical approaches and algorithms for drug discovery. In 2000, Prof. Goldblum won the first award of the ACS Computers in Chemistry Division in the Emerging Technologies competition for the novel algorithm he devised for solving extremely complex combinatorial problems. This algorithm, later named Iterative Stochastic Elimination (ISE), has been extremely effective in the discovery of novel drugs by Prof. Goldblum and his team in diverse fields such as obesity, diabetes, cancer, immunology, Alzheimer’s disease and toxicology. ISE also enabled the discovery of mupirocin as a candidate for systemic delivery by liposomes.

Dr. Ahuva Cern, Ph.D.

In parallel to her role at AMRazor, Dr. Cern is a researcher at the Laboratory of Membrane and Liposome Research at the Hebrew University. Previously, Dr. Cern was an associate director at Pharmos Ltd. She then became Director of the Formulation Development Laboratory at Nextar Chempharma Solutions, where she managed many formulation development projects for pharma and biotech companies. Dr. Cern received her Ph.D. from the Hebrew University, working in the laboratory of Prof. Barenholz and Prof. Goldblum in the Department of Biochemistry. Her Ph.D. thesis focused on computational models for the identification of drugs suitable for liposomal delivery.