[nanoPost] Porous nanoparticles for various encapsulation applications

The Platform: Porous-Particle Nanodevice

Porous Nanoparticles

The companies platform nanotechnology (i.e. nanosponge) device for the treatment of cancer is a highly porous particle produced using an advanced material formation process.  The porous particle structure is currently filled with a therapeutic/cytolytic agent and the particles are injected into a specific body fluid.  The nano-sized particles are randomly shaped, generally ellipsoidal with a particle size in the range of 100nm to 5nm.  Continuous pores in the particles can range in size from 10-200nm.

The company’s materials are highly porous (porosity greater than 90%) so a large dose of therapeutic agent (encapsulant) can be loaded into the pores of the nanoparticle.  The dose is much larger than could be coated on the particle surface of the same size or possibly incorporated into a degradable solid particle.

During the particle fabrication process, a “stealth” coating can be formed on the surface of the particles that allows them to circulate for extended time periods in body fluids.  A ligand coating can also be added following fabrication to facilitate particle binding to target cells that over-express a specific receptor, such as tumour cells.  Further, a contrast agent can be incorporated during fabrication to facilitate imaging of the particles through magnetic resonance following binding to the target tissue.

Following injection, body fluids surround the particle and fill the pore structure by capillary action.  Another coating can be placed over the therapeutic agent within the pores to delay therapeutic agent hydration.  This delay of agent hydration protects it from being degraded by material in the body fluid.  The agent is released from the particles after they bind to the target cells. The protective/delay layer thereby maximizes the amount of agent that is delivered to the target cell.  This released agent provides an intended therapy; and following agent release, the particle slowly biodegrades or is removed by natural means.

The nanodevice effectively acts as a “ferry” to carry agent to the tumour site.  The key advantage of this approach is that the agent is not exposed directly to the body fluid because it is inside the pores and it is coated with a delay coating.  This sequestering of agent reduces the agent being degraded by body fluids and also minimizes interaction of the agent with the body’s immune system components (e.g. macrophages, neutrophils, anti-bodies).  The resultant effect is a more potent delivery of agent and less of a chance for eliciting an immune response.

To fabricate the multifunctional therapeutic nanodevice shown, several key staff capabilities are required, namely the ability to: 1) Form micro and nano-sized porous particles, 2) Incorporate a stealth coating material and possibly a contrast agent in the particles during fabrication, 3) Determine particles properties including size, shape, porosity, pore size, and stealth coating density, 4) Coat a targeting ligand on the particle surface for targeted therapy, 5) Fill the particle’s pores with a therapeutic agent (encapsulant), and test its release characteristics, 6) Provide a coating to protect the agent and delay its release, 7) Determine the ligand coating density, and 8) Test various aspects of the particle in vitro and in vivo (e.g., circulation time, tissue biodistribution, and tumor regression in animal models).

As mentioned previously, key factors in delivery a therapeutic agent to a targeted site is precision in timing of circulation within the body as well as timely release of the agent to the cells/tumours of interest.  Previous work performed by the staff at the company and its collaborators have shown that these criteria can be met through in vitro and in vivo models.