For oral/depot/intravenous delivery of proteins and hydrophobic molecules, and controlled-release small molecules and vaccine antigens
Hydrophobic Microspheres – The Opportunity and the Problems
Biologically adherent polymeric microsphere carriers are effective in the oral delivery of proteins such as insulin and DNA plasmids. These microspheres are comprised of hydrophobic copolymers, in contrast to conventional microspheres that are hydrophilic in nature. The hydrophobic microspheres appear to have a significantly longer residence time in the gastrointestinal tract compared to conventional microspheres.
While highly promising, the hydrophobic microspheres still present challenges in terms of manufacturing and formulation of a clinically acceptable product. Typically, the microspheres are produced from an organic solvent solution, which raises concerns about deleterious effects on the therapeutic protein and residual organic solvent in the final product.
A Solution – SuperFluids™ Polymer Nanospheres – PNS
Aphios has avoided these difficulties by utilizing supercritical, critical or near-critical fluids with or without polar cosolvents (SuperFluids™ [SFS]) to form mono-disperse Polymer Nanospheres (PNS). These nanospheres are utilized to encapsulate proteins with controlled-release characteristics without the usage of toxic organic solvents.
The PNS Process
The polymer is dissolved in the SuperFluids™ phase and decompressed through a nozzle into an aqueous solution containing the therapeutic target.
Alternatively, the polymer-enriched SuperFluids™ stream can be mixed with the targeted therapeutic in solution at operating pressures, and the mixture is then decompressed into an aqueous solution, liquid nitrogen or empty vessel (spray dryer).
As a third option, the polymer-enriched SuperFluids™ stream can be mixed with the targeted therapeutic nanoparticles slurry at operating pressures, and the mixture is then decompressed into an aqueous solution, liquid nitrogen or empty vessel (spray dryer).
- Biodegradable polymer nanospheres for the nanoencapsulation and controlled release of therapeutic proteins and viral vaccine antigens can be manufactured without utilizing organic solvents as is traditionally done.
- The use of SuperFluids™ instead of organic solvents, such as ethyl acetate and methylene chloride, reduces exposure of encapsulated therapeutic proteins and vaccine antigens to potentially denaturing organic solvents.
- The use of SuperFluids™ eliminates the potential need for removal of any residual organic solvents in the final drug product.
- By changing nozzle design and process parameters, the process can be utilized to customize the manufacture of polymer nanospheres/microspheres for a specific target.
- In addition to reduction or elimination of organic solvent usage, use of supercritical fluids imparts advantages of product sterility under conditions for which we have demonstrated the microbicidal and virucidal effects of supercritical fluids.
- PNS is a single-step process that is scalable.
The PNS biodegradable polymer nanospheres technology platform can be used for the oral delivery of therapeutic proteins and the subcutaneous controlled release of vaccine antigens.