LPM™ Leuprolide
LPM™ (Lipid Polymer Micelle)
The LPM™ technology is a drug-delivery platform technology for oral administration that uses reverse micelles stabilized by polymers. Reverse micelles are generally described as a lipid system and are similar to water-in-oil emulsions in that the hydrophilic lipid head groups are directed towards the micelle core, with the hydrophobic tails imbedded in the oil phase. This results in a drug-delivery system that is a thermodynamically stable clear dispersion of the water-soluble drug in the lipid phase. But unlike water-in-oil systems, stabilized reverse micelles do not depend on the presence of other surfactants and are thermodynamically stable. In the LPM™ system, water-soluble drugs are contained in the water space in the core of the micelles and are protected against degradation.
LPM™ is thought to promote intestinal absorption through the action of the micelles to open up small channels that allow only molecules of a certain dimension to pass through, excluding extremely large molecules, bacteria and viruses. The reverse micelles also structurally prevent the rapid inactivation of peptides by enzymes in the upper gastrointestinal tract. Other sensitive drugs that can be delivered orally with the LPM™ system include various classes of drugs such as peptides, nucleic acids and proteins, which are degraded in the stomach and small intestine.
Oral Leuprolide Utilizing LPM™
Soligenix anticipates proceeding towards clinical development of an oral form of the peptide hormone drug leuprolide using the LPM™ technology. Leuprolide is a synthetic peptide agonist of gonadotropin releasing hormone (GnRH) that is used in treatment of endometriosis in women and prostate cancer in men. In preclinical studies in rats and dogs, Soligenix has demonstrated that the LPM™ technology results in high systemic bioavailability of intestinally absorbed leuprolide. In both animal models, the bioavailability of leuprolide ranged from 20 to 40 percent, compared to 2.2 percent for the control oral solution. Leuprolide is one of the most widely used anti-cancer agents for advanced prostate cancer in men. Injectable forms of leuprolide marketed under tradenames such as Lupron® and Eligard® had worldwide sales of approximately $1.8 billion in 2006. Injectable leuprolide is also widely used in non-cancer indications, such as endometriosis in women (a common condition in which cells normally found in the uterus become implanted in other areas of the body), uterine fibroids in women (noncancerous growths in the uterus) and central precocious puberty in children (a condition causing children to enter puberty too soon). Leuprolide is currently available only in injectable, injectable depot and subcutaneous implant routes of delivery.
Soligenix has received a European patent which addresses its Lipid Polymer Micelle (LPM™) technology for the improved oral delivery of drugs. The issued European patent, EP 1460992, entitled "Stabilized Reverse Micelle Compositions and Uses Thereof" covers lipid structures (reverse micelles) that promote the intestinal absorption of peptides and other sensitive drugs that cannot otherwise be given orally. Corresponding patents in the United States and elsewhere are currently pending.
