Smart Nanocarrier Systems for Diabetic Wound Healing: Preclinical Innovations and Clinical Progress in Drug and Gene Delivery

Diabetic wounds represent a complex clinical challenge arising from the convergence of chronic inflammation, impaired angiogenesis, oxidative stress, neuropathy, infection, and dysregulated extracellular matrix remodeling. Conventional therapies targeting single pathological components have shown limited efficacy, underscoring the need for integrated and mechanistically informed treatment strategies. This review comprehensively examines nanocarrier-mediated drug delivery systems as a transformative platform for diabetic wound management, integrating herbal, synthetic, semi-synthetic and gene-based therapeutics across preclinical and clinical landscapes. Emphasis is placed on the molecular pathophysiology of diabetic wounds and how advanced nanocarrier platforms enable spatiotemporal control, enhanced bioavailability, and pathway-specific modulation of inflammatory, angiogenic, antimicrobial, and regenerative processes. Material-driven functionalities, including stimuli-responsive release and multifunctional hybrid systems are critically discussed in relation to disorder-specific wound phenotypes. Furthermore, the review evaluates current preclinical models, translational barriers and emerging clinical trends, highlighting the importance of patient stratification and precision wound nanomedicine. Collectively, this work positions nanocarrier-based therapeutics as a promising and adaptable approach capable of addressing the biological heterogeneity of diabetic wounds and advancing toward clinically meaningful outcomes. Keywords: angiogenesis; diabetic wounds; gene therapy; herbal therapeutics; nanocarriers; wound healing