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Purpose <p>Drug-coated balloon (DCB) therapy is a promising approach to treat peripheral artery disease (PAD), wherein lesion site preparation, balloon inflation, and the local delivery of anti-proliferative drugs such as paclitaxel (PTX) restores and retains lumen patency. Although largely successful in PAD applications, broader clinical deployment is in part limited by the occurrence of late lumen loss due to inward vessel remodeling at the treatment site, a maladaptive chronic response that has been clinically-observed to coincide with elevations in resident vascular smooth muscle cell (vSMC) tone. This study aims to explore a novel strategy to improve DCB efficacy via drug-based attenuation of vSMC tone at the treatment site.</p> Methods <p>As a strategy to mitigate this post-DCB failure mode, we consider the local co-delivery of PTX and an additional drug that induces relaxation of vSMCs, specifically the clinically-approved anti-hypertensive drug valsartan (VAL). The potential benefit of drug-based regulation of vSMC tone is supported by recent theoretical studies that predict inward remodeling in the presence of hypertension and endothelial cell dysfunction, both common co-morbidities in PAD patients and established causes of elevated vSMC contractility. The specific selection of VAL as the anti-contractile payload constituent is motivated by its well-known pharmacokinetic and safety profiles, and the notion that current clinical use and familiarity could promote rapid translation in the context of DCBs.</p> Results <p>Our obtained results quantify the potency of VAL to induce local vSMC relaxation in arterial tissue, demonstrate the feasibility of PTX and VAL co-delivery using the canonical excipient urea for balloon coating formation, and elucidate key structure-function relations to facilitate efficient drug delivery with these novel coatings.</p> Conclusion <p>Our study supports the continued evaluation of VAL for inclusion in DCB formulations due to its potential to redirect post-treatment arterial remodeling. Future in-vivo studies which examine the co-delivery of PTX and VAL in the context of DCBs are needed to establish both the safety and efficacy of this novel approach.</p>

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Towards the Integration of an Anti-Contractile Compound Within Drug-Coated Balloon Therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月25日

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  • Dima BaniHani,
  • John F. Eberth,
  • Francis G. Spinale,
  • Vipul C. Chitalia,
  • Jahid Ferdous,
  • Vijaya B. Kolachalama,
  • Tarek Shazly

摘要

Purpose

Drug-coated balloon (DCB) therapy is a promising approach to treat peripheral artery disease (PAD), wherein lesion site preparation, balloon inflation, and the local delivery of anti-proliferative drugs such as paclitaxel (PTX) restores and retains lumen patency. Although largely successful in PAD applications, broader clinical deployment is in part limited by the occurrence of late lumen loss due to inward vessel remodeling at the treatment site, a maladaptive chronic response that has been clinically-observed to coincide with elevations in resident vascular smooth muscle cell (vSMC) tone. This study aims to explore a novel strategy to improve DCB efficacy via drug-based attenuation of vSMC tone at the treatment site.

Methods

As a strategy to mitigate this post-DCB failure mode, we consider the local co-delivery of PTX and an additional drug that induces relaxation of vSMCs, specifically the clinically-approved anti-hypertensive drug valsartan (VAL). The potential benefit of drug-based regulation of vSMC tone is supported by recent theoretical studies that predict inward remodeling in the presence of hypertension and endothelial cell dysfunction, both common co-morbidities in PAD patients and established causes of elevated vSMC contractility. The specific selection of VAL as the anti-contractile payload constituent is motivated by its well-known pharmacokinetic and safety profiles, and the notion that current clinical use and familiarity could promote rapid translation in the context of DCBs.

Results

Our obtained results quantify the potency of VAL to induce local vSMC relaxation in arterial tissue, demonstrate the feasibility of PTX and VAL co-delivery using the canonical excipient urea for balloon coating formation, and elucidate key structure-function relations to facilitate efficient drug delivery with these novel coatings.

Conclusion

Our study supports the continued evaluation of VAL for inclusion in DCB formulations due to its potential to redirect post-treatment arterial remodeling. Future in-vivo studies which examine the co-delivery of PTX and VAL in the context of DCBs are needed to establish both the safety and efficacy of this novel approach.