Nanotechnology to revolutionise drug delivery

- Last updated on GMT

Related tags: Drug delivery, Nanotechnology

The emergence of nanotechnology is likely to have a significant
impact on drug delivery sector, affecting just about every route of
administration from oral to injectable, according to specialist
market research firm NanoMarkets.

And the payoff for doctors and patients should be lower drug toxicity, reduced cost of treatments, improved bioavailability and an extension of the economic life of proprietary drugs, according to Michael Moradi, an associate analyst at the company.

"This is an impressive list [but] also impressive is the fact that many of the categories of nano-enabled drug delivery systems are already close to or at the point of marketing,"​ unlike many of the 'futuristic' applications claimed for nanomedicine, he said.

NanoMarkets expects the dosing benefits of nano-enabled drug delivery systems to be extended to compounds used in treating both infectious disease and cancer, and has identified six types of drug delivery systems in which nanotechnology is likely to have a significant impact.

For injectable drugs​, nanotechnology is already generating new dosage forms that are easier to administer, more pleasant for the patient receive and confer a competitive advantage in the marketplace.

For example, at the start of this year Johnson & Johnson revealed that Elan's NanoCrystal technology would be used in a Phase III clinical trial for an injectable formulation of paliperidone palmitate, a drug for schizophrenia, notes Moradi. This is a new 'nano formulation' of an older drug which overcomes the original's insolubility, by reducing the particle size to under 200 nm.

Nanotechnology is also opening up new opportunities in implantable delivery systems​, which are often preferable to the use of injectable drugs, because the latter frequently display first-order kinetics (the blood concentration goes up rapidly, but drops exponentially over time). This rapid rise may cause difficulties with toxicity, and drug efficacy can diminish as the drug concentration falls below the targeted range.

In contrast, implantable time release systems may help minimize peak plasma levels and reduce the risk of adverse reactions, allow for more predictable and extended duration of action, reduce the frequency of re-dosing and improve patient acceptance and compliance.

Nanotechnology adds to these the benefits, says Moradi. Citing pSivida's BioSilicon product, he notes that this nanostructured material effectively stores an active compound in nanosised pockets that release minute amounts of drug as the silicon dissolves. pSivida is currently exploring biodegradable implantable methods for tissue engineering and ophthalmic delivery.

Nano-implants will also be used in the not-too-distant future for treating cancer. Among the first nanoscale devices to show promise in anti-cancer therapeutics and drug delivery are structures called nanoshells, which NanoMarkets believes may afford a degree of control never before seen in implantable drug delivery products.

Nanoshells typically have a silicon core that is sealed in an outer metallic core. By manipulating the ratio of wall to core, the shells can be precisely tuned to scatter or absorb very specific wavelengths of 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. A physician can use infrared rays to pass harmlessly through soft tissue, while initiating a lethal application of heat when the nanoshells are excited.

Some researchers are also experimenting with temperature-sensitive drug delivery control methods, using nanoshells that release their payload only when illuminated with the proper infrared wavelength.

Despite these advances, the vast majority of consumers prefer an oral drug delivery system​ to implantables or injectables. With this in mind, various development groups are working to enhance traditional oral delivery systems with nanoengineered improvements.

"There are some areas where nano-enhanced drugs could make a big difference in increasing oral bioavailability and reducing undesirable side effects. By increasing bioavailability, nanoparticles can increase the yield in drug development and more importantly may help treat previously untreatable conditions,"​ notes Moradi.

Because of the blood brain barrier (BBB) many new chemical entities aimed at treating brain disorders have proved not to be clinically useful. Nanoparticles have been demonstrated to cross the BBB with little difficulty and companies such as Germany's NanoPharm have developed systems capable of reaching the brain for anaesthesia (Dalargin; an analgesic), cancer drugs, and various other therapeutics.

The company claims several advantages over existing systems, including no requirement to open the BBB, the ability to deliver potentially any drug, whether hydrophilic or hydrophobic, and no need to modify the drug itself, which may affect its activity.

Meanwhile, researchers at the University of Texas at Austin have described a means of using nanospheres for oral drug delivery. These nanosphere carriers are derived from hydrogels, which are highly stable organic compounds that swell when their environment becomes more acidic. They have been successfully formulated into controlled-release tablets and capsules, which release active compounds when the hydrogel body swells.

NanoMarkets also suggests that nanomaterials provide a unique opportunity for rapid topical delivery​ of active compounds. Given their very small size, nanoparticles are able to enter human tissues and cells quickly, and companies such as Novavax have already developed regulated topical systems that take advantage of the unique properties of micellar nanoparticles.

Novavax has is developing two hormone replacement therapies, called Estrasorb (which received FDA approval in October 2003) and Androsorb which successfully completed Phase I human trials in 2003.

Meanwhile, the number of FDA-approved polymers available for use on skinis increasing rapidly, according to Moradi, so the industry has been presented with opportunities to create new transdermal platform​ designs with improved 'on-skin' properties and diffusion of active molecules compared to current patches.

This interesting trend is expected to result in smaller and less invasive patches that increase the universe of available drug candidates,"​ according to Moradi. In some cases, he adds, electronics are even being integrated into patch-like platforms involving wound care, monitoring, and diagnostic methods.

Finally, nanotechnology is finding new applications in the area of toxin removal​. Colloidal dispersions have been demonstrated to remove potentially lethal compounds from the bloodstream, including high concentrations of lipophilic therapeutics, illegal drugs, and chemical and biological agents.

A team of scientists at the University of Florida and Clarkson University in Potsdam, New York, has demonstrated favourable results to this end, using biocompatible microemulsions. These oil-in-water systems have a rapid and efficient absorption capacity for many target molecules that are frequently overdosed, whether this be intentional or accidental. The microemulsions use a polymeric surfactant, in combination with an ionic co-surfactant.

NanoMarkets believes that not only will the nano-enabled drug delivery market be one of the first true nanomedicine markets to evolve, but as it does so, the revenues from nanoenabled drug delivery systems will be quite large.

Related topics: Ingredients, Delivery technologies

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