Abstract
<jats:p>Drug repurposing has produced a substantial preclinical literature on chronic wound healing, yet almost none of it has reached the clinic. Statins, antidiabetic agents, anticonvulsants, selective serotonin reuptake inhibitors and beta-blockers all promote re-epithelialisation, angiogenesis and collagen deposition in animal models of impaired healing, but each shares a physicochemical liability that the original oral indication never had to solve: they must cross the stratum corneum and remain at the wound bed in therapeutic concentration. This review examines the intersection where that problem is being addressed, namely the encapsulation of repurposed systemic drugs into nanocarriers designed for cutaneous delivery. Sixteen distinct drug-carrier combinations reported between 2020 and 2026 are catalogued and compared, spanning solid lipid nanoparticles, nanostructured lipid carriers, liposomes, spanlastics, cubosomes, nanosponges, nanoemulgels, electrospun nanofibres and microneedle arrays. Reported gains in transdermal flux range from 1.5-fold to 8-fold over conventional gels, with corresponding reductions in time to wound closure. Two observations emerge from the comparison. First, simvastatin alone has been formulated into at least six structurally distinct nanocarriers by independent groups, with no head-to-head study establishing which architecture is superior for a defined wound type. Second, evaluation methodology is not standardised: donor phase, membrane choice and receptor medium differ so widely between reports that flux values cannot legitimately be pooled. The mechanistic convergence of these agents on macrophage polarisation and vascular endothelial growth factor signalling suggests that carrier selection, not drug selection, is now the rate-limiting variable. Recommendations are made for comparative formulation studies, harmonised in vitro permeation protocols, and a quality-by-design framework consistent with current regulatory expectations for nanomedicines.</jats:p>