Nanoparticle composite glasses deliver drugs where they’re needed

Many of our most effective medicines have a range of side effects, with chemotherapy being a classic example of how debilitating side effects can limit treatment options. Most side effects, including those associated with chemotherapy, are the result of medicines interacting with otherwise healthy parts of the body. To limit these problems, researchers are developing methods that deliver medications only to localized regions of the body. Directed drug delivery focuses medications to the diseased areas of the body, thus dramatically reducing side effects and increasing drug effectiveness.

Directed delivery methods are as varied as the diseases they intend to cure, and various methods for achieving specificity have been the subject of research for decades. One area that's received increasing attention is magnetic particle delivery. In magnetic particle delivery, magnetic nanoparticles are injected into the body while an external magnetic field is applied to direct the particles to the area of interest.

Unfortunately, attaching medications to magnetic particles can be difficult or impossible and, as a result, mesoporous bioactive glasses have been proposed for use in directed drug delivery. Pore space in these glasses is filled with dissolved or liquid medications that are released through diffusion in the body. This simple drug loading mechanism means that almost any drug can be delivered, but there is no mechanism for guiding these materials to specific parts of the body.

In the August edition of Acta Materialia, researchers at the Shanghai Institute of Ceramics and National Institute of Advanced Industrial Science and Technology in Japan report synthesis of a magnetically active composite that combines a mesoporous bioactive glass with Fe₃O₄ nanoparticles to form what the authors call magnetic and mesoporous bioactive glass (MMBG). This composite combines the magnetic properties of Fe₃O₄ nanoparticles with the flexible drug loading mechanism of mesoporous bioactive glasses.

The researchers produced MMBG using a well-established technique called evaporation induced self assembly (EISA). An organic source of silicon, tetraethoxysilane (TEOS), was mixed with a surfactant (P123, if that means anything to you), ethanol, HCl, and Ca²⁺, P⁵⁺, and Fe^2+/3+ salts. The ethanol was driven off through evaporation and the surfactant caused the TEOS and salts to self-assemble into a highly ordered, three-dimensional array of amorphous solid and empty pore space. Upon heating to 700^oC, the Si⁴⁺, Ca²⁺, and P⁵⁺ form a bioactive CaO-SiO₂-P₂O₅ glass while the Fe segregates to form discrete, crystalline Fe₃O₄ nanoparticles. Clearly, this work relies on some help from thermodynamics in that the Fe segregates to form Fe₃O₄ nanoparticles instead of being incorporated into the glass.

These nanoparticles provide the magnetic part of the MMBG that may allow it to be directed throughout the body. The researchers found that the Fe₃O₄ nanoparticles exhibited superparamagnetism, an effect seen only in certain magnetic nanoparticles that dramatically increases their response to magnetic fields.

The empty space formed during self assembly remained an interconnected network of 3.5 nm diameter pore channels. This pore space is critical for two reasons: it can be occupied by drugs and will allow the body to more rapidly decompose and eliminate the glass after the drug has been delivered. 

To introduce a medication, the MMBG can be immersed in a solvent containing the drug of choice (in this study, Ibuprofin dissolved in hexane) as capillary action draws the liquid into the pore channels. When the drug-infused MMBG is placed in bodily fluids, the drug is released through diffusion. This ingeniously simple approach means that any drug that can be dissolved in a liquid that wets the glass can be delivered with this system.

In this composite, we have a decidedly simple directed delivery system that, by virtue of the synthesis method, EISA, may also prove to be very flexible. By varying the amount and chemistry of solvent and surfactant in the system, a wide array of pore sizes, morphologies, and three-dimensional structures can be achieved. These may allow higher drug loading as well as more control over delivery kinetics.

Also, the EISA process has been used with a wide array of glass compositions so the surface chemistry of the MMBG can be altered to add more functionality or better control of the processes that eventually break down and eliminate the glass from the body. It should be noted that only three compositions, one type of pore morphology, and one type of drug have been tested in this paper, but the flexibility of the synthesis process implies that this work may open the door to a diverse range of drug delivery applications in the future.

 Acta Materialia, 2008. DOI:10.1016/j.actamat.2008.03.013