Evaluating the potential of ultrasound-assisted compression for crafting implantable drug delivery systems

Abstract

This study aimed to evaluate the feasibility of using ultrasound-assisted compression (USAC) for manufacturing implantable drug delivery systems (IDDS). USAC integrates the principles of traditional compression techniques with the application of ultrasound waves. The combined mechanical pressure and thermal energy generated by this technology result in material heating, melting, and sintering. This work investigates how the combination of ultrasound waves and a formulation comprising thermoplastic polyurethane (TPU) and low molecular weight polycaprolactone (L-PCL) influences the final properties of an implantable device designed for the sustained release of dipyridamole (DIP).

The USAC-fabricated implants were thoroughly characterized to assess the material properties and the impact of the USAC technique. A comprehensive analysis was performed, including microscopy techniques such as Raman microscopy, acoustic microscopy, scanning electron microscopy (SEM), and optical coherence tomography (OCT), as well as X-ray Microcomputer Tomography (μCT). Additionally, thermal analysis, along with Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), was performed to assess the interactions between the components and evaluate the crystallinity of the materials. Moreover, the mechanical properties and DIP release profiles of the implants were evaluated to study the feasibility of the USAC technique for manufacturing IDDS.

The results suggested that the resulting materials were homogeneous, and non-covalent interactions between DIP and TPU were identified. These materials offered an attractive option for preparing TPU-based implantable devices due to their mechanical properties. Indeed, the addition of DIP in concentrations up to 20 % did not influence the compression modulus. In vitro release study demonstrated that the USAC-fabricated implants exhibited a sustained drug release profile throughout the 4-week study. Nevertheless, implants containing lower DIP loading exhibited a higher percentage release (6.29 %) compared to those with higher DIP loading (4.28 %), suggesting that the drug may be interacting with TPU within the USAC implantable devices, potentially limiting the release of DIP.

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Materials

Medical grade Tecoflex™ EG-72D thermoplastic polyurethane (TPU) was kindly supplied by Lubrizol Advanced Materials (Barcelona, Spain). Low molecular weight PCL (CAPA™ 2054, MW = 550 Da), henceforth referred to as L-PCL, were provided by Perstorp (Malmö, Sweden). Dipyridamole (DIP) was acquired from Tokyo chemical Industry (Oxford, UK). Phosphate buffered saline (PBS) tablets to prepare PBS solution (pH 7.4) and ethanol were both purchased from Panreac AppliChem ITW Reagents (Barcelona, Spain). All materials and reagents were used as received.

Mónica Millán-Jiménez, Elena Sánchez Díaz, Gloria Mora-Castaño, Qonita Kurnia Anjani, Adela García-Martín, Isidoro Caraballo, Eneko Larrañeta, Juan Domínguez-Robles, Evaluating the potential of ultrasound-assisted compression for crafting implantable drug delivery systems, Journal of Drug Delivery Science and Technology, Volume 110, 2025, 107056, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2025.107056.