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The design and printing of 3-dimensional (3D) networks has gained significant interest in recent years, particularly in the area of drug dosage development. A team of researchers from the UK and China has now developed a electrohydrodynamic (EHD) printing technique to fabricate efficient tetracycline hydrochloride (TE-HCL) aligned-fibre antibioticpatches that can be used for drug delivery applications.

Polymer-based dosage forms are one of the most studied in drug delivery systems and many properties can be tailored from their flexible nature. New approaches to polymer-based drug delivery systems have produced many novel technologies over the recent years, including those that produce polymer fibres. One of the most common and well known polymer fibre fabrication methods is electrospinning. Electrospinning has previously been postulated for drug delivery systems but lacks one key component- it produces 2D architectures with complex alignments, whereas 3D networks, with ordered alignments, are required to hold the drug in such applications.

Traditionally, the production of 2D fibres with random orientations has produced carriers with a high deviation in their drug release kinetics and a broad diameter range. Such fibrous drug carriers also have to be cut or shaped to form the required geometry.

3D printing of drug dosage forms is an emerging area, and so far, electrohydrodynamic (EHD) printinghas shown the most promise. EHD printing is a variation of standard electrospinning techniques, and was developed to enable the orientation of fibres. This method has a much greater control and fibre formation, which can be tailored to produce a specific geometry without the need for cutting- an ideal property for drug delivery purposes.

The printing of complex 3D networks has been tried and tested by many different methods, but unlike EHD, many are limited by low structural resolution, number of processing steps, drug leaching or active instability. EHD also offers a high resolution and a one-step fabrication process to 3D print complex structures at room temperature.

EHD functions by depositing single fibres to fabricate a pre-determined 3D structure, through a layer-by-layer (LbL) method. The whole process is made possible by shortening the deposition distance to less than 10 mm and 3D ordered fibres are the result.

Ideal wound dressing patches should be moderately hydrophilic, porous, biodegradable and mechanically stable. Without the ability to tailor such properties, the drug release is inefficient. This EHD printing method is flexible and controllable enough to be able to control the properties of the patch.

Printing the 3D Patches

The pre-printing solution for the fibres in the 3D patch were produced by a one step process, using polycaprolactone (PCL), Polyvinyl pyrrolidone (PVP) and Tetracycline hydrochloride (TE-HCL). The fibres were printed using a custom-built printer, using a predetermined pattern, a flow 0.2-0.8mlh-1 and an electric potential of 1.5-3 kV. The patches were characterised using a scanning electron microscope (SEM) (Hitachi), optical contact angle and interface tension meter (SL200KB, Kino Industry CO. Ltd), Fourier transform infrared spectroscopy (FTIR) (IR Affinity 1, Shimadzu), tensile tests (Zwick/Roell Z020) and water contact angle (WCA) measurements.

The drug loaded 3D patches are made up of perfectly aligned fibres in a fibrous strut orientation, a variable inter-strut pore size and a controllable film width. Various techniques confirmed that there was successful TE-HCl loading into the patch, with patches containing PVP and TE-HCl molecules displaying an enhanced hydrophobicity. It was also found that changes under mechanical tension arise from additive effects and the pore size within the patch was crucial to effective antibiotic release behaviours.

20 layers were printed to make up the patch, with dimensions of 50×10 mm. The patches contain active pores that are utilised for drug loading. The drugs were loaded, and encapsulated with minimal loss during the printing process, with a loading efficiency of 97-98%. The initial drug loading of these patches was found to be 106.4 ± 21.2 μg to 375.2 ± 21.5 μg, depending on the wt% of TE-HCl in the patch. For the following 5 days, 88.3 ± 1.2% of the active drug was found to be released.

By using the EHD printing method, the researchers enabled the patches to be controllable in terms of its size, dimension, pore volume, drug loading and thickness. This flexibility is an ideal property for on-demand, bespoke film engineering. It also provides an exciting opportunity to tailor the drug dosage forms with minimal preparation and operational processes. Therefore, this patch has a great potential to develop dosage forms for various anatomical sites, where using conventional pharmaceuticals has proved challenging and require a personalised approach.

Source:

Wang J-C., Zheng H., Chang M-W., Ahmad Z., Li J-S., Preparation of active 3D film patches via aligned fiber electrohydrodynamic (EHD) printing, Scientific Report, 2017, 7, 43924

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