Introduction:
Nanotechnology in the Pharmaceutical Industry
Part 4 of 4: Inorganic Nanoparticles
The successful formation of nanoparticles is markedly formulation technique driven. In order to impart all the advantages of nanotechnology over tradition medicines, the formulation technique used is as, if not more, important than the individual components (excipients) used. Historically successful techniques include (a) top-down: where materials are mechanically broken down to nano-sized (e.g., homogenization and nanomilling); (b) bottom-up: where nanomaterials are assembled from a solution of smaller components (e.g., solvent evaporation and precipitation), & (c) self-assembly: spontaneous organization of particles through non-covalent interactions (e.g., microfluidics and dialysis).
We love nanotechnologies and want you to love them too. In this 4-part series, we will introduce some of the well-established nanoparticle technologies, highlighting their benefits. We’ll conclude each part of the series discussing emerging technologies we think are noteworthy. Today in Part 4, we’ll discuss Inorganic Nanoparticles.
Part 4: Inorganic Nanoparticles
Inorganic nanotechnology is a wide-ranging category with applications across the medicinal diagnostic and material sciences. Often overlooked is their application in the pharmaceutical industry, including drug delivery in the traditional sense, and therapies where the inorganic material is itself the therapeutic. Drugs are inherently toxic—as Paracelsus’ maxim expresses “the dosage alone makes it so a thing is not a poison”. However, many of the metals used in inorganic nanotechnology are particularity neurotoxic and, or carcinogenic, which makes their application perilous. This is why they are often seen as a last resort, and we at Callan Pharma Services generally recommended other nanotechnologies instead. Nevertheless, inorganic nanotechnologies have niche applications. Below we discuss 4 categories of inorganic nanotechnologies whose unique properties make them worth the risk.
- Metal Nanoparticles – This category covers the pure metallic elements, most often those with low toxicity, such as gold and silver. These are size-dependent technologies in which the enhanced surface area imparted with processing gives the metals their therapeutic properties—often constructed bottom-up. For example, the Turkevich method involves the reduction of tetrachloroauric acid (HAuCl4) with sodium citrate to yield gold nanoparticles. ACTICOAT™ FLEX is an example of an application of metal nanoparticle technology. It’s a wound dressing that integrates nanocrystalline silver which serves as an antimicrobial agent. The nanocrystalline silver is embedded in a polyester mesh, which facilitates the controlled release of the antimicrobial agent.
- Metal Oxide Nanoparticles – Oxides of metals are often exceptionally stable, making them excellent choices for nanotechnologies. The predominant use of metal oxides in the pharmaceutical industry is as excipients in oral dosage forms (e.g., iron oxide, and magnesium oxide). However, applications are expanding, with FERAHEMEÒ (ferumoxytol) serving as an example. It’s a colloid constructed form iron oxide layered with decorated with PSC (polyglucose sorbitol carboxymethyl ether), which stabilizes and shields it from mononuclear phagocyte system (MPS). Semi-synthetic polysaccharide coating is what gives the drug its controlled release aspect. Originally approved as an intravenously delivered iron replacement therapy, it is now used off-label as an MRI contrast agent due to its superparamagnetic properties.
- Ceramic Nanoparticles – Ceramics are renowned for their diverse construction, stability, and biocompatibility. Tunable surface physiochemical properties are what makes them so attractive to the pharmaceutical industry. Charge variability, hydrophilicity or hydrophobicity, and covalent attachment of ligands with potential targeting properties are all achievable with ceramic nanoparticles. A success story is EPSOLAY® (benzoyl peroxide). This is a topical cream approved for the treatment of the inflammatory lesions of rosacea. The cream contains microcapsules composed of silicon dioxide, cetrimonium chloride, and polyquaternium-7 which slowly releases benzoyl peroxide in a tolerable manner.
- Quantum Dots – these are nano-sized semiconductor particles with unique photoluminescence properties. Most often associated with the material sciences, in particular QLED (Quantum Dot Light Emitting Diode) technology used in TVs. Clinical success has been limited but companies like 2C Tech are making meaningful advances. They are an ophthalmic disease-focus company developing quantum dot technology which they hope can act as miniature light converters to stimulate photoreceptors cells in the retina. They advanced an intravitreal injection of a cadmium/selenium 655 quantum dot to the clinical stage to evaluate use in the treatment of retinitis pigmentosa (RP) which is a genetic disease that causes vision loss due to the progressive degeneration of photoreceptor cells in the retina.
Emerging Technology: Theranostic Gadolinium-based Nanoparticles
The future of inorganic nanotechnology in medicine is the combined therapeutic and diagnostic (‘theranostic’) application. Real time imaging of diseases tissues coupled with a targeted, therapeutic effect. NH TherAguix is a French company advancing gadolinium-based nanoparticles with combined therapeutic (radiosensitization) and MRI diagnostic properties. AGuIX® is their lead drug candidate comprised of matrix of polysiloxane and gadolinium (Gd) chelates, with applications in the treatment of glioma and glioblastoma brain tumors. The nano characteristics allow for accumulation in brain tumors via the enhanced permeation and retention (EPR) effect, while also allowing for renal clearance. The paramagnetic gadolinium is frequently employed in MRI and is used here to visualize brain tumors in real time. Gadolinium also acts to amplify ionizing radiation (x-rays) and thus radiation-induced DNA damage to kill cancer cells.
