Lumi-Solve technology

Lumi-Solve technology

Lumi-Solve is a first in-class targeted drug-eluting balloon photo-angioplasty device developed for lower limb revascularisation in patients with peripheral arterial disease (PAD). Lumi-Solve technology involves ultrasonic coating of an angioplasty balloon with a novel UV-activated anti-neointimal hyperplasia (NIH) epigenetic drug (c-Metacept-3) together with a triple lumen catheter facilitating a Swiss fibre-optic-driven activation mechanism whilst preserving the guidewire in-situ throughout the entire procedure. Lumi-Solve improves on current drug-eluting balloon (DEB) technology through enhanced safety and efficacy.

Lumi-Solve represents a first-in-class photo-activated DEB device, and is a clear,
innovative advance in the evolution of angioplasty therapy

The history of Lumi-Solve

Metacept-3

Metacept-3 (MCT-3), a novel histone deacetylase inhibitor (HDACi) first synthesised in the laboratory in 20061, demonstrated profound anti-neointimal hyperplasia activity and significantly decreased toxicity compared to paclitaxel (PTX).2

DEBs coated with Metacept-3

Subsequent studies evaluated MCT-3-coated DEBs in an ovine model of NIH, demonstrating a more potent anti-NIH effect compared to PTX in vivo alongside molecular evidence of reduced vessel wall cellular proliferation and inflammation.3

Epi-Solve DEB attenuates left common carotid artery (LCA) NIH. Con = untreated, PABA = plain balloon angioplasty, PTX = PTX DEB, MCT-3 = Epi-Solve DEB. **p < 0.01, ***p < 0.001 vs. Con, n = 4–8.

Epi-Solve DEB attenuates LCA NIH. Con = untreated, PABA = PABA, PTX = PTX DEB and MCT-3 = Epi-Solve DEB. (i) 20× magnification, scale bar = 1.0 mm. (ii) 80× magnification of area outlined in (i), scale bar = 300 μm. (iii) 20× magnification Verhoeff–Van Gieson staining, scale bar = 1.0 mm. I = neointima, M = media.

Conjugated MCT-3

To facilitate targeted, safer MCT-3 activation during DEB deployment, a novel, UV (365nm) light-activated analogue of MCT-3 (c-MCT-3) was developed. c-MCT-3 demonstrated low toxicity pre- and post-UV activation as well as reduced toxicity compared to both MCT-3 and PTX.4 Thus, c-MCT-3 was the perfect candidate for the development of our new photo-activated DEB device, 'Lumi Solve'.

Chemical structure of conjugated MCT-3 and production of MCT-3 on UV365nm exposure.

Toxicity, potency and identification of cMCT-3 +/-UV. Untreated (Con) and 24hr 1.0mmol/l cMCT-3 pre-UV, 1.0mmol/l cMCT-3 post 4 min UV365nm (cMCT3+UV), 1.0mmol/l PTX and 1.0mmol/l MCT-3 treated human umbilical vein endothelial cells (HUVEC), *p<0.001 vs. PTX, p<0.05 vs. MCT-3 (n=3-4).

Lumi-Solve

Activation of ultrasonically-coated c-MCT-3 DEBs was achieved utilising custom-designed Swiss fibre optic technology to deliver UV-365nm light from the Prizmatix light source to the Lumi-Solve balloon, thereby facilitating targeted vessel wall activation of the chemical payload at the time of DEB deployment.

In vivo activation of Lumi-Solve has been demonstrated5 with ongoing studies to evaluate Lumi-Solve efficacy and safety currently being undertaken.

The three components of Lumi-Solve: Prizmatix light source, Swiss fibre-optics and ultrasonically-coated angioplasty balloon.

Lumi-Solve in action

The following video demonstrates the full process of Lumi-Solve activation.

Lumi-Solve-T: Overcoming the guidewire port and shadowing problems

Using the guidewire port to deliver fibre-optic light to the drug coated angioplasty balloon is associated with several problems included blood reflux into the guidewire lumen and wire removal.

To solve these problems a triple lumen version of Lumi-Solve has been designed with a dedicated third port to enable passage of the fibre-optic into the balloon. A conventional parallel guidewire fibre-optic port design is associated with significant guidewire shadowing6 (see figure) which will reduce light transmission to the balloon surface and drug activation.

Guidewire (GW) shadowing of fibre-optic (F) light

Lumi-Solve-T is a novel triple lumen catheter and hub designed to overcome the problems associated with guidewire shadowing and will facilitate uninterrupted and complete balloon surface irradiation and maximum drug activation7.

Lumi-Solve-T in action

-

References

  1. Dear AE, Liu HB, Mayes PA, Perlmutter P. Conformational analogues of Oxamflatin as histone deacetylase inhibitors. Org Biomol Chem. 2006;4(20):3778-84. View
  2. Rahmatzadeh M, Liu H, Krishna S, Gaspari T, Welungoda I, Widdop R, et al. A Novel Agent with Histone Deacetylase Inhibitory Activity Attenuates Neointimal Hyperplasia. Cardiovasc Drugs Ther. 2014;28(5):395-406. View
  3. Liu H , Byrne M, Perlmutter P, Walker A, Sama GR, Subbiah J, et al. A Novel Epigenetic Drug-Eluting Balloon Angioplasty Device: Evaluation in a Large Animal Model of Neointimal Hyperplasia. Cardiovasc Drugs Ther. 2019;33(6):687-92. View
  4. Sama GR, Liu H, Mountford S, Thompson P, Robinson A, Dear AE. Synthesis and biological evaluation of a novel photo-activated histone deacetylase inhibitor. Bioorg Med Chem Lett. 2020;30(16). View
  5. Liu H, Sama GR, Robinson A, Mountford S, E Thompson P, Rodda A, et al. Design, Development, In Vitro and Preliminary In Vivo Evaluation of a Novel Photo-Angioplasty Device: Lumi-Solve. Cardiovasc Eng Technol. 2021. View
  6. Menon A, Subasic de Azevedo I, Choong K, Bhatnagar D, Wang C, Sluka P, et al. Advances in Design and Development of Lumi-Solve: A Novel Drug-Eluting Photo-Angioplasty Device. Cardiovasc Eng Technol. 2023 Aug;14(4):605-614. View
  7. Tria A, Dharma A, Spiegel L, Rodda A, Allada A, Sluka P, Menon A, Prabaharan E, Wettesinghe P, Adams J, Spanger M, Dear AE. Design and Prototyping of a Novel Triple Lumen Photo-Angioplasty Device: Lumi-Solve-T. Cardiovasc Eng Technology. 2025 Apr;16(2):211-221. - View