Aphios Corporation has developed a process for making biodegradable polymer nanospheres utilizing supercritical, critical or near-critical fluids w/wo polar cosolvents (SuperFluids™). These nanospheres are utilized to encapsulate proteins with controlled-release characteristics without usage of toxic organic solvents.
Biologically adherent polymeric microsphere carriers have been shown to be effective in the oral delivery of proteins such as insulin and DNA plasmids (Mathiowitz et al., 1997). 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 as 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.
Aphios has avoided these difficulties by utilizing SuperFluids to form mono-disperse polymer nanospheres as illustrated in the adjacent table. In vitro release characteristics of insulin from polymer nanospheres was evaluated by re-suspending lyophilized nanospheres in phosphate buffered saline (PBS) at a pH of 7.4. Absorption of the solution was then measured at 280 nm at different time intervals. Release characteristics of insulin from these polymer nanospheres over a 5-½ hour period is shown in the adjacent figure.
An in vivo study of a similar batch of nanoencapsulated insulin conducted in diabetic mice showed a significant decrease in glucose levels after oral administration, causing statistical decreases in glucose levels at 1, 2 and 4 hours post administration. Injected insulin also resulted in statistically decreased glucose levels; while injectable insulin, given orally, did not cause statistical decreases in glucose levels.
Aphios SuperFluids polymer nanospheres (PNS) process can be utilized to encapsulate therapeutic proteins and other molecules without utilizing organic solvents as is traditionally done. By changing nozzle design and process parameters, the process can also be utilized to manufacture polymer microspheres. SuperFluids PNS is a single-step process that is scalable.