Protein Nanoparticles - PNP

For oral/subcutaneous/pulmonary delivery of hydrophobic drugs, proteins, peptides, genes and vaccine antigens

Conventional Protein Nanoparticles Techniques and their Drawbacks

An ongoing concern in the pharmaceutical and biotechnology industries is the administration of a steady dosage of a therapeutic agent. In the formulation of controlled release therapeutics, it is frequently desirable to disperse the material into very fine, uniform particles. Such particles may then be advantageously incorporated into controlled-release delivery vehicles such as polymeric nanospheres/microspheres, depots or implantable devices, or delivered to the lungs as an aerosol. With proteinaceous therapeutics, the generation of such fine particles is particularly problematic with several drawbacks.

Method Drawbacks
Mechanical Milling Protein denaturation by mechanical shear and/or heat

Spray Drying

Protein denaturation at gas-liquid interface and/or heat for solvent vaporizaton
Fluid Energy Grinding High velocity gas can yield electrostatically charged powders, size reduction inefficient for soft proteinaceous powders
Lyophilization Broad size distribution, protein specific applicability and protocols
Anti-Solvent Precipitation Protein denaturation by organic, solvents, solvent removal, solvent residuals, particle size control difficult
Salt Precipitation Protein specific applicability, salt removal or contamination, particle size control difficult

A Solution – The PNP Process

PNP-Process-Diagram sm

Protein Nanoparticles (PNP) technology platform utilizes the expansive energy of supercritical fluids with or without polar cosolvents (SuperFluids™ [SFS]) to disaggregate or comminute protein crystals and amorphous powders into monodisperse nanoparticles [US Patent].

The PNP process uses SuperFluids™ to form small protein particles without first dissolving the material in a liquid solvent. As such, the target therapeutic retains full activity and is devoid of residual processing chemicals such as solvents, salts or surfactants. The energy necessary for the size reduction is derived from a rapid depressurization of the SuperFluids™. The low temperature generated by the expansion of the supercritical fluid helps to preserve the chemical integrity of the protein and is an advantage over conventional grinding processes that generate heat.

Benefits/Advantages of the PNP Process

  • Forms monodisperse protein particles [0.5 to 5 micron (μm)] without having to first dissolve the protein in a liquid solvent
  • Robust for a wide range of enzymes & sizes
  • High retention with possible enhancement of bioactivity
  • Not constrained by limited solubility in benign solvents such as ethanol that may be used with other supercritical fluid techniques, and the utilization of large volumes of liquids that limits other techniques such as spray drying
  • Produces a Joule-Thompson cooling effect, and thus avoids heat associated with milling techniques that can cause protein degradation and contamination by metal particles
  • Improves processes and products in the area of drug delivery, e.g., more uniform and extended release of therapeutic from microsphere carriers or more uniform aerosol formulations
  • Improves product quality with no residual solvent or surfactant contamination
  • Environmental advantages due to elimination of the use of organic solvents.
  • Physical, single step, single-pass process that is scalable
  • Improves process economics due to simplification of the process train

Applications of the PNP Process

Aphios' protein nanoparticles (PNP) process can be used for oral/subcutaneous/pulmonary delivery of hydrophobic drugs such as paclitaxel, camptothecin and betulinic acid, proteins such as insulin, calcitonin and human growth hormone, peptides, genes and vaccine antigens for anthrax, HIV and influenza.

Partnering Opportunity

Contact us if you are interested in conducting a feasibility study and/or establishing a research and development partnership.

White Paper

Interested in reading more? Request this white paper.