SEM images of porous hemispherical silicon particles under different magnifications.
Leonardo has created a library of first stage nanoporous silicon particles of specific porosity, shape, size, and surface properties to handle a wide variety of applications. The first stage can be loaded with different second stage nanoparticle delivery vehicles to generate custom drug delivery solutions. The second stage can be loaded with pharmaceuticals ranging from highly toxic or insoluble chemotherapy agents to delicate biological molecules, and drug release rates can be tuned from days to weeks.
The human body maintains a sophisticated series of defense mechanisms to guard against infection and toxicities. Unfortunately, these mechanisms prevent many therapeutics from reaching their intended sites of action. A variety of white blood cells are present in the blood stream to engulf infectious agents like bacteria and viruses before they can infect sensitive tissue. The walls of normal blood vessels present a physical barrier to particles above a certain size and cells are selective in passing molecules through their membranes. The ability of a therapeutic to elude each bio-barrier is highly dependent on its physical, chemical and biological properties including size, shape, surface chemistry, and density. Leonardo designs and produces multistage silicon-based nanoparticles that circumvent each bio-barrier and provide dramatic increases in access to tumor cells. Leonardo has developed a leadership position in the emerging science known as "transport oncophysics" through its expertise and experience in hemodynamics (the branch of physiology dealing with the forces involved in the circulation of the blood) and rational delivery system design.
Nano- and micro- sized particles preferentially accumulate in tumors due to the porous nature of the blood vessels that feed them and many nanoparticle drug delivery systems have been designed to take advantage of this effect. Leonardo has achieved results that surpass single stage delivery systems. Leveraging the vast technical know-how to shape silicon developed for the computer industry, Leonardo's MSV™ technology improves the efficiency of drug delivery, while also providing a substantial reduction in systemic toxicity side effects. Leonardo uses proprietary mathematical algorithms to design multi-stage delivery particles that not only circumvent the multiple bio-barriers between infusion and the interior of a target cell, but also provide a maximum payload delivery and controlled release properties required to effectively treat the challenging cancer types which continue to plague our society.
Leonardo has THE paradigm shifting treatment approach in the industry and is now ready to attack the challenging metastatic cancers which have so far defeated the “best in class” cancer treatments currently in the market place. Recent animal studies have shown the ability to substantially improve the performance of several approved drug compounds, which opens up significant partnering potential and potential to speed up the approval of the new MSV™ delivery system approach.
Advantages of Leonardo's multistage system
Leonardo's first stage carriers have been designed, developed, fabricated, and refined to surmount the delivery limitations encountered in the current generation of nanoparticle drug delivery systems, including:
- Precise manufacturing control over the size and shape of the MSV particles which produces optimally shaped particles that have passive, natural targeting capabilities with both inflamed tissues and tumor fenestration sites.
- Active targeting capability with multiple ligands and aptimer coatings are also available to further increase concentrations in challenging environments such as Pancreatic and Bone Cancer locations.
- The payload capacity of a MSV™ particle is more than 800 times larger than typical spheroidal nanoparticles used today, which provides the ability to deliver a sustained release of an effective dosage level in a particle microenvironment for a 2-3 week period.
- The flexibility of the MSV™ particle structure to load and protect small molecules, such as doxorubicin and paclitaxel, as well as more sensitive payloads such as siRNA's for genetic targeting, and larger payloads such as Gold Nanoshells used with thermal ablation applications.
- Precise control over MSV™ pore size and surface charge allows for a wide variety of second stage carrier release profiles, independent from the ability to effectively load the second stage particles and drug compounds.
- The discoidal shape and large payload MSV™ particles provide a “Direct Diffusion Capacity” advantage that is several orders of magnitude greater than current spherical nanoparticle systems. This allows the particle to establish a substantial, long term “Micro Cmax” zone in cancer sensitive areas, while keeping the systemic Cmax levels low enough to minimize side effects.