Pharma Voice

Nanoparticulate drug delivery

B R Kirupakar talks about the market impact of nanoparticle drug delivery system on pharmaceutical industry and the strategies for patenting nanotechnology

The market impact of nanoparticle drug delivery system on pharmaceutical industry will be widely felt, ranging from new specialised treatment for exotic diseases to re-engineering common OTC pain relievers. These new delivery systems will disrupt the generic drug market, since pharmaceutical companies can repackage their brands with expired patents along with newly patented delivery system, so that generics can no longer claim to be brand name equivalents. A recent study of patent activity for nanoparticles in drug delivery shows a clear increasing trend in issued patents (check graph).

Oral delivery of active compounds is expected to remain the primary means of administering drugs for the pharmaceutical industry. A large portion of nano-technology R&D funding will be used in the development of these systems. This will be one of the big success stories in nano-technology-enabled drug delivery. Nano-enabled drug delivery system has high prospects in areas like encapsulation technologies, implantable delivery method, imaging agents and micro-needles.

Nanoparticle based delivery system would allow faster drug absorption, controlled dosage release into the human body and would have other unique properties of minimising side-effects by eliminating requirement of co-solvent as used in conventional dosage form. Further, drugs that have side-effects due to triggering an immune system response can be wrapped in nanoparticle coating and prevent immune system from recognising and reacting to a foreign substance.

Psividas biosilicon is a nanostructured drug delivery system that allows drug molecules to be held in nanosised particles that release a tiny pulse of drug as the biosilicon dissolves. This is the same material as the microchip that runs a cell phone or computer and has application to a variety of drugs that have problematic delivery and bioavailability characteristics. Biosilicon can be favoured for oral drug delivery system because of its resistance to degradation in acid environment.

Nanotech strategies

Dental compounds are made from titanium and zirconium and these structures can be coated on the inside, outside or both with active pharmaceuticals to provide controlled release characteristics. Nanoscale devices show promise in anti-cancer therapeutics and drug delivery nanoshells. These nanoshells have a silicon core that is sealed in an outer metallic ore. By manipulating ratio of the wall to the core, the shells can be tuned to scatter or absorb specific wavelength of the light. For example, gold encased nanoshells have been used to convert light into heat, enabling the destruction of tumours by selective binding to malignant cells.

Because of Blood Brain Barrier (BBB), many new chemical entities aimed at treating brain disorder have proved not to be clinically useful. Nanoparticles have demonstrated to cross the BBB with little difficulty and companies like Germany's NanoPharm have developed systems capable of reaching the brain for anaesthetic, cancer drugs and various other therapeutics. Researchers at the University of Texas at Austin have described a means of using nanosphere for oral drug delivery. These nanosphere carriers derive from hydrogels, which are highly stable organic compounds that swell when their environment becomes watery. They have been successfully formulated into CR tablets or capsules, which release active compounds when the hydrogel body swells. A team of scientists at the University of Florida demonstrated application of nanotechnology in the area of toxin removal. This is oil-in-water micro emulsion, which use a polymeric surfactant in combination with an ionic co-surfactant and have rapid and efficient absorption capacity for many target molecules that are frequently overdosed, be it intentional or accidental.

Nano patents

Nanotechnology is still in its infancy and filing nanotech patents has become a patent grabbing excercise. Since the prior art is sparse to non-existent, for many of the new discoveries in nanosciences, broad patents are being issued especially in areas such as nano pharmaceuticals and nano biotechnology.

As the companies seek to bring newer technology to market, a number of disputes over potentially overlapping patents can arise. So far, there have been few nanotech patent disputes because companies are yet to commercialise their nanotechnology discoveries. In light of potential market value of nanoparticle based drug delivery systems, companies are trying to get broad patent rights. There are few companies in the market and they will face considerable uncertainty with potentially overlapping patent held by others.

However, the first way to resolve a patent dispute is by having clearly described patent that boxes out competition. A strategic patenting approach starts even before invention is described. Scientists and researchers need to be schooled in the ways of spotting inventions and documenting them. Laboratory notebook documentation is critical. If anything ends up being patentable, dates for its conception should be documented, as these dates will become crucial in patent disputes. Public disclosures undermine a company's ability to obtain foreign patent protection since foreign patent office does not allow one-year grace period after its public disclosure unlike US.

To obtain maximum patent protection, nanotech companies can choose to file 'quick and dirty' provisional patent applications. This is a relatively new concept, which allows inventors to provide an application containing the description of an invention, but does not include claims. A key step in getting rid of a patent litigation is by fully understanding what else is in the field.

A thorough prior art search or freedom to operate search with assistance of skilled engineers and attorney with multi-faceted knowledge in physics, medicine, chemistry and engineering will almost avoid infringement litigation. Many disputes occur because the patent does not use standard language that clearly signals what a patent covers. Particularly, nanotechnology is a difficult topic to discuss due to the growing proliferation of the 'nano' term, as well as the confusion surrounding the definition of this new area of technology. Despite nanotechnology's potential in improving the way drugs are being developed and delivered, pharmaceutical companies are pledging almost no money or people to nanotechnology research. This will expose us to strategic risks as other sectors invest in this technology. If this trend continues, nanotech will play out in pharmaceuticals just as biotechnology did. We have to contend with a new wave of super branded generics that will erode market share.

(The writer is with Exela Pharmasci, Bangalore as Senior Research Officer)