A new type of controlled-release drug-delivery vehicle made from nanostructured polymer membranes has been unveiled by researchers at the University of California at San Francisco in the US. The device, which releases its therapeutic payload slowly and continuously over a period of several months, could come in useful for a wide variety of drug-delivery applications in the body including in difficult-to-access areas like the back of the eye and limb joints.
One of the most important applications of nanomedicine is drug delivery using tiny drug-carrying vehicles. Such vehicles are normally made of hollow nanoparticles in which therapeutic molecules can easily be transported. However, nanostructured membranes in which the drug is loaded between a nanofilm and a backing layer also show promise. The advantage of the membrane option is that drug molecules around the same size as the membrane pores (which can range from tens of nanometres to hundreds of nanometres across) can be released slowly thanks to the fact that they travel through the pores in a single file.
Until now, most such nanostructured membranes have been made from inorganic materials, such as silicon, alumina or titania because they are relatively easy to fabricate. However, the problem is that these materials are generally rigid and often not biodegradable. Polymeric nanostructured membranes could come into their own here, say Tejal Desai and colleagues, who have been studying biodegradable polymers like poly(caprolactone) (PCL) as the active element in drug-delivery systems capable of controlled release.
By templating the PCL off a zinc oxide mould, the researchers succeeded in fabricating nanostructured PCL membranes containing nanosized pores that were able to release the model therapeutic protein immunoglobuline G (IgG) over the course of several months.
Desais team create the nanostructured features of their membranes by spin casting a thin film of PCL and poly(ethylene glycol) (PEG) onto a ZnO template that penetrates the thickness of the polymer film. Under appropriate conditions the PEG forms an interconnected network that spans the supporting PCL film layer. When the PEG is removed, a porous PCL film is generated and the ZnO template can subsequently be etched with acid to generate individual nanostructured PCL pores. The technique is described in Nano Letters.
We showed that functional proteins, like IgG, can be released steadily and at a constant rate over a period of four months, Desai told nanotechweb.org. Such sustained and controlled release has never been achieved before with other such biodegradable film devices and will be important for maintaining therapeutic concentrations of a drug in the body for long periods of time.
The amount of drug released can also be controlled by changing the membrane surface area smaller membranes release smaller amounts of drug, for example.
These devices might be used to deliver drugs in various parts of the body, and particularly into confined and hard-to-reach spaces where long-term delivery might be needed such as the back of the eye or in spaces between joints, said Desai.
The team is currently looking at using its device to deliver drugs to the retina in an effort to control and treat age-related macular degeneration.
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Nanodevice delivers drugs in hard-to-reach places