Aphios Corporation

SuperFluids^TM CFN — Phospholipid Nanosomes

Aphios Corporation has developed an improved process utilizing SuperFluids™ for the formation of small, uniform liposomes (nanosomes) to improve the delivery and therapeutic efficacy of poorly water-soluble drugs while reducing their toxicities [U.S. Patent No. 5,776,486, July 07, 1998; U.S. Patent No. 5,440,055, August 08, 1995; European Patent No. 0792143, September 04, 2002; and European Patent No. 703,778, May 07, 1997].

CFN Apparatus In Aphios’ SuperFluids™ critical fluid nanosome (CFN) process, SuperFluids™ at appropriate conditions of pressure and temperature are utilized to solvate phospholipids, cholesterol and other nanosomal raw materials in an apparatus such as that shown in the adjacent figure. A circulation pump is utilized to ensure good mixing between the SuperFluids™ and nanosomal raw materials in an upper high-pressure loop. After a specific residence time, the resulting mixture is decompressed via a back-pressure regulator (valve) though a dip tube with a nozzle into a decompression chamber (vessel B) which contains phosphate-buffered saline or other biocompatible solution. This SuperFluids™ CFN injection technique is ideally suited for the nanoencapsulation of proteins, DNA and small hydrophilic drugs.

In a second SuperFluids™ CFN technique, the phospholipids and the target compound are solvated simultaneously in a SuperFluids™ “cocktail,” which is dispersed continuously into an aqueous environment. The process stream is decompressed, and the unstable phospholipid bilayer fragments collide and rapidly seal to form nanosomes, entrapping the compound. The controlling parameters for this process are pressure and rate of decompression. The decompression technique is readily scaled to larger production volumes. It is a “one-step” process, and the SuperFluids™ stream composition can be designed to achieve concentrated phospholipid and target compound feed streams. The results are high trapping efficiencies and concentrated product recovery streams in the SuperFluids™ CFN decompression technique.

In a third technique, SuperFluids™ CFN evaporation can be uniquely utilized to encapsulate very hydrophobic molecules such as the potent anticancer drug paclitaxel, camptothecin, a very effective topoisomerase-I inhibitor and other anticancer and anti-HIV therapeutics such as bryostatin 1. In this technique, the hydrophobic drug(s) and the phospholipids are directly solvated in the SuperFluids™ prior to injection into a phosphate-buffered saline or other biocompatible solution. After decompression through a nozzle, the SuperFluids™ evaporate off leaving an aqueous solution of nanosomes entrapping hydrophobic molecules within their lipid bilayers.

Aphios has utilized SuperFluids™ CFN to develop nanosomal formulations of paclitaxel, Taxosomes,^™ camptothecin, Camposomes,™ and other poorly water-soluble therapeutics.