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Chen, Xin, De Grandi, Davide, Zhu, Yonglian, Lutheryn, Gareth, Lane, Majella E., Sil dos Santos, Bruno and Carugo, Dario (2024) Ultrasound-compatible 3D-printed Franz diffusion system for sonophoresis with microbubbles. International journal of pharmaceutics, 666 (124749). pp. 1-12. ISSN 0378-5173
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.
Available under License Creative Commons Attribution 4.0.
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