Ultrasound-compatible 3D-printed Franz diffusion system for sonophoresis with microbubbles.

Chen X., De Grandi D., Zhu Y., Lutheryn G., Lane ME., Da Silva Sil Dos Santos B., Carugo D.

Sonophoresis is a topical drug delivery approach that utilises ultrasound as a physical stimulus to enhance permeation of active pharmaceutical ingredients through the skin. Only limited research has however been conducted to evaluate the potential of ultrasound-responsive drug carriers, such as gas microbubbles, in sonophoresis. Franz diffusion cells have been extensively used for measuring drug permeation in vitro; however, traditional systems lack compatibility with ultrasound and only limited characterisation of their acoustical behaviour has been carried out in previous research. To overcome this limitation, we designed and manufactured a novel Franz cell donor compartment coupled with a conventional glass receptor, and performed a functional characterisation of the assembly for application in sonophoresis with ultrasound-responsive agents (specifically imiquimod-loaded gas microbubbles). The donor was fabricated using a photoreactive resin via 3D printing and was designed to enable integration with a therapeutically relevant ultrasound source. The assembly was capable of effectively retaining liquids during prolonged incubation and the absorption of imiquimod onto the 3D-printed material was comparable to the one of glass. Moreover, a predictable ultrasound field could be generated at a target surface without any significant spatial distortion. Finally, we demonstrated applicability of the developed assembly in sonophoresis experiments with StratM®, wherein ultrasound stimulation in the presence of microbubbles resulted in significantly enhanced drug permeation through and partitioning within the membrane (2.96 ± 0.25 μg and 3.84 ± 0.39 μg) compared to passive diffusion alone (1.74 ± 0.29 μg and 2.29 ± 0.32 μg), over 24 h.

DOI

10.1016/j.ijpharm.2024.124749

Type

Journal article

Publication Date

2024-12-05T00:00:00+00:00

Volume

666

Keywords

3D printing, In-vitro diffusion system, Microbubbles, Sonophoresis, Ultrasound, Microbubbles, Printing, Three-Dimensional, Skin Absorption, Drug Delivery Systems, Imiquimod, Diffusion, Administration, Cutaneous, Ultrasonic Waves, Skin

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