Polymer Nanospheres (PNS) Characteristics and Applications

For oral/depot/intravenous delivery of proteins and hydrophobic molecules, and controlled-release small molecules and vaccine antigens

In Aphios' PNP Process, biodegradable biopolymers are dissolved in SuperFluids™, mixed with the target in an aqueous solution or as a slurry of nanoparticles at operating pressures, and the mixture is decompressed into an aqueous solution, liquid nitrogen or an empty vessel (spray dryer); as result of decompression, polymer nanospheres are formed, encapsulating the therapeutic target.

In Vitro Characteristics of PNS

  • Polymer nanospheres of an HIV antigen had an average mean diameter 247 nm with a SD of 100 nm, as measured by a Coulter 4NMD Submicron particle size analyzer.
  • In vitro release characteristics of insulin from polymer nanospheres were evaluated by re-suspending lyophilized nanospheres in phosphate-buffered saline 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.
Characteristics SuperFluids-PNS-In-Vitro-Time-Release-of-Insulin sm

In Vivo Characteristics of PNS

  • Three groups of four chronic diabetic BB/Wor male rats were used to evaluate efficacy of polymer nanoencapsulated insulin. One group was given 2 mL of the test formulation using standard gavage method. A second group received oral non-encapsulated insulin, administered by gavage at the concentration based on the animals' day of diabetes onset. A third group received injected insulin (PZI, Eli Lilly) therapy at the dose consistent with their day of onset of diabetes. The animals were bled prior to treatment and at 0.5, 1, 2, 4, 8, and 16 hours after treatment.

    This in vivo oral gavage study 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.

    This insulin gavage in vivo study supports the use of PNS for the oral delivery of proteins.

    • Anthrax recombinant protein antigen (rPA) polymeric nanospheres were lyophilized and stored at 5ºC during transportation and storage. Female adult A/J mice (Harlan, UK) were immunized once with a 20 µg dose in 0.1 mL intra-muscularly (groups of 5). The mice were then challenged on day 21 with 103 maximum lethal dose (MLD) equivalent to 106 colony forming units (CFU) of Bacillus anthracis STI strain spores intraperitoneally (IP). Survival was monitored over the subsequent 14 days.
  • All the vaccinated mice survived the challenge, indicating preservation of immunogenicity for the nanoencapsulated antigen. Results are encouraging in that rPA encapsulated in biodegradable polymer nanospheres was fully protective.

    This anthrax antigen in vivo study supports using PNS for the subcutaneous delivery of vaccine antigens.

PNS Applications

Polymer Nanospheres – PNS – enabling technology platform can be used for oral/depot/intravenous delivery of proteins such as insulin, salmon calcitonin, erythropoietin [EPO], interferon α, and hydrophobic molecules such as paclitaxel and other taxoids, and Δ9-THC.

PNS can also be used for controlled-release of small molecules and vaccine antigens such as influenza, HIV and anthrax recombinant protein antigen.

Partnering Opportunity

Contact us if you are interested in evaluating this technology for your application.

We will conduct feasibility studies to evaluate the use of our PNS technology platform for your therapeutic candidates and/or products utilizing micrograms to milligrams of API (active pharmaceutical ingredients) on a laboratory scale.

PNS-Characteristics Researcher-and-PNS-Apparatus sm



Interested in viewing this patent? Request a copy here.