Nanoscale drug depots for long-term sustained release of drugs.Rather like Goldilocks, researchers have devised a nano-sized fiber that can deliver drugs just right. Many nanoscale delivery systems give an initial burst release of their drug cargo – leading to a higher than desirable concentration in the blood – followed by a gradual tailing off – providing lower than necessary levels. But the fibers developed by Deng-Guang Yu, Gareth R. Williams, and co-workers can deliver a drug in a uniform manner [Yang et al., Acta Biomaterialia (2017), doi: 10.1016/j.actbio.2017.01.069].
The fibers consist of a solid core of a model drug, ferulic acid (FA), surrounded by an insoluble polymer commonly used in biomedicine, cellulose acetate (CA). With a diameter of just 500 nm, the fibers create nano-sized reservoirs of the drug surrounded by a polymer coating.
“The fibers have an insoluble polymer shell containing a partially-crystalline drug core, so the rate of drug release is controlled by the rate at which the drug can diffuse through the polymer shell,” explains Williams, who led the research at University of Shanghai for Science and Technology. “Since the shell is insoluble, the diffusion rate does not change with time – and so the rate of drug release is constant.”
The so-called nano-sized drug depots show a constant rate of release for the model drug FA over more than 36 hours. And the fibers have another advantage too.
Nanoscale drug delivery systems are usually fabricated using ‘bottom-up’ approaches such as chemical synthesis or molecular self-assembly. But these methods can be time-consuming and difficult to scale up. Yu and his colleagues wanted to use a simpler route, so they turned to electrospinning.
The process involves ejecting a solution of a polymer through a fine needle under the influence of an electric potential, which serves to evaporate the polymer and produce solid fibers. But in a novel twist, the researchers developed a tri-axial approach to enable the simultaneous spinning of the drug through a central needle surrounded by the polymer, which is ejected through a second needle, along with a solvent to stop the needles clogging.
“The processing of one liquid in electrospinning is well known, but working with three liquids is much less explored,” says Williams.
The novel zero-order drug depots have a wide range of potential applications for oral or implantable medicines – for example for daily dosages of metformin for treating type 2 diabetes or drug-delivery stents for heart attack patients.
“The application of our fibers is very practical in the medium term,” says Williams. “The key obstacle to overcome will be that of scale-up.”
Electrospinning of single liquids is possible on an industrial scale, but research and development will be needed to realize tri-axial processes.