For intravenous and/or topical administration of hydrophilic molecules including siRNA and hydrophobic anticancer drugs

We utilize five different critical fluid nanosomes (CFN) techniques for the nanoencapsulation of therapeutics.

• CFN Injection. In the CFN injection process, SuperFluids™ (SFS) are first utilized to solvate phospholipids and other liposomal raw materials. Phospholipid liposomes are then spontaneously formed by decompressing the SFS mixture into a biocompatible solution. This technique is ideally suited for the nanoencapsulation of proteins, siRNA and small hydrophilic therapeutics.
• CFN Co-Injection. As an example of CFN co-injection, siRNA in a buffer is co-injected into the discharged lipid-enriched SFS stream upstream of a static inline mixer prior to the intermixed streams being discharged into the decompression chamber containing a buffer. The experiment is designed to simultaneously discharge a specific amount of lipid mixture and siRNA in a pre-specified ratio into the receiving buffer in the decompression chamber. The flow rates of both the lipid-enriched SFS stream and the siRNA-rich stream, and their ratios were varied.
• CFN Decompression. In a third 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 liposomes, entrapping the target compound. The decompression technique is readily scaled to larger production volumes.
• CFN Evaporation. In a fourth technique, the hydrophobic drug(s) and the phospholipids are directly solvated in the SuperFluids™ prior to injection into a biocompatible solution. After decompression through a nozzle, the SuperFluids™ evaporate off, leaving an aqueous solution of liposomes entrapping hydrophobic anticancer drugs such as paclitaxel, Taxosomes®, and camptothecin Camposomes™ within lipid bilayers.
• CFN Co-Encapsulation. CFN can also be used to co-encapsulate Top1 inhibitors (such as camptothecin) and Tdp1 inhibitors (such as neomycin) in phospholipid nanosomes. Camptothecin is quite hydrophobic and will be packaged in the lipid bilayer. Neomycin is quite water-soluble and will be packaged in the aqueous core of phospholipid nanosomes. Inhibiting Tdp1 has the potential to enhance the anticancer activity of Top1 inhibitors and to act as antiproliferative agents.

Optionally, pegylated phospholipids can be utilized to provide steric hindrance, increasing residence time and therapeutic index. Phospholipids spliced into specific antibodies can be utilized to target nanosomes to specific cancers in the colon, lung or ovary to reduce toxicities.

CFN Applications

CFN can be used for intravenous and/or topical administration of hydrophilic molecules including siRNA, hydrophobic anticancer drugs such as paclitaxel, Taxosomes®, camptothecin Camposomes™, Bryostatin-1, Bryosomes™, betulinic acid, Albasomes™, doxorubicin, and CNS disorder drugs such as Δ9-THC and nanosomalTHC™.