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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s13239-025-00798-7","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T16:20:46Z","timestamp":1753460446000},"page":"611-623","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Towards the Integration of an Anti-Contractile Compound Within Drug-Coated Balloon Therapy"],"prefix":"10.1007","volume":"16","author":[{"given":"Dima","family":"BaniHani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John F.","family":"Eberth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis G.","family":"Spinale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vipul C.","family":"Chitalia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jahid","family":"Ferdous","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijaya B.","family":"Kolachalama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarek","family":"Shazly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"798_CR1","doi-asserted-by":"publisher","unstructured":"Madhavan MV, Stone GW. 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