By Rachelle H.B. Fishman

BioWorld International Correspondent

JERUSALEM ¿ An Israeli team has demonstrated that it can overcome the impasse of tissue-targeted delivery of virtually all drugs by manipulating the charge environment of oil-impregnated water emulsions of the drugs.

Those efforts have aroused interest among companies such as Bayer AG, of Leverkusen, Germany, and NicOx SA, of Sophia-Antipolis, France, as well as a large Swiss pharma company whose name is still confidential because negotiations are in progress.

The Yissum Research Development Co. of the Hebrew University of Jerusalem has registered two worldwide patents on the technology. And a new French biotechnology company, Novagali SAS, founded in August 2000 in Evry, has obtained the license to develop the technology for all commercial therapeutic and pharmaceutical purposes. Novagali plans to raise between $20 million and $25 million during the first quarter of 2002.

Shimon Benita, professor in the school of pharmacy at the Hebrew University, who developed the drug delivery technique, told BioWorld International, ¿Now lipophilic drugs ¿ those soluble in fatty or oily solutions but not in water ¿ can penetrate all normally charged membranes and reach their intended targets, where their benefit is maximal and side effects minimal.¿

All biological membranes are negatively charged. When the positively charged oil emulsion encapsulating a drug molecule is introduced into a tissue, it can be literally attracted by electrostatic action through the membrane. ¿This means that there is better penetration for the drug even through mucous membranes of the intestine and eye, as well as through skin,¿ said Benita, who was awarded a prestigious Kaye Prize for Innovations and Inventions at the Hebrew University in June.

Benita developed the technology and elaborated on it during the last two years with his students and postdoctoral fellows.

¿We have effectively applied the new techynology to cyclosporin A in a rabbit model of dry eye. Other investigators had shown that cyclosporin applied to the cornea and especially conjunctiva can relieve dry-eye syndrome, but application by drops was ineffective because of limited penetrability,¿ Benita said. ¿During the last 18 months, we optimized the cyclosporin emulsion formulation, and demonstrated by pharmacokinetic monitoring that the concentration of the drug in both cornea and conjunctiva were significantly higher than with a negatively charged emulsion,¿ he added.

Benita said that more than 30 million people worldwide suffer from medium and severe dry-eye syndrome, in which ¿liquid tears¿ only temporarily ease the most overt symptoms without providing any hope of cure for the underlying illness.

Since its inception in August 2000, two French venture capital companies have invested EUR4 million in the project.

Clinical testing is anticipated to begin within a few months. Novagali is preparing to set up GMP production of drug batches for toxicity and clinical evaluation. Benita said that toxicity studies are expected to start in the first quarter of 2002, and, ¿if all goes as planned, clinical studies will commence during the last quarter of 2002.¿

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