AI-assisted design of green nanocarriers for targeted drug delivery in chronic wounds

Abstract

Chronic wounds represent a persistent clinical challenge owing to their complex pathophysiology, including prolonged inflammation, microbial infection, impaired angiogenesis, and delayed tissue regeneration. Conventional therapeutic approaches often exhibit limited efficacy due to poor drug bioavailability, inadequate retention at the wound site, and off-target effects. Nanocarrier-based drug delivery systems have emerged as promising strategies for improving therapeutic outcomes; however, concerns regarding synthesis-associated toxicity, scalability, reproducibility, and clinical translation continue to limit their widespread application. This review critically examines the emerging convergence of green nanotechnology and artificial intelligence (AI) for chronic wound management. Green nanocarriers, synthesised using biocompatible and renewable materials through environmentally sustainable processes, offer potential advantages over conventionally fabricated nanomaterials, including reduced toxicity and improved biocompatibility. Nevertheless, the rational design and optimisation of such systems remain challenging due to the multifactorial nature of wound healing and nanomaterial-biological interactions. AI- and machine learning (ML)-based approaches provide opportunities to support formulation development by enabling predictive modelling of synthesis parameters, physicochemical properties, drug loading efficiency, release behaviour, and nano-bio interactions. This review discusses the pathological features of chronic wounds, including oxidative stress, biofilm formation, dysregulated matrix metalloproteinase activity, and altered wound microenvironmental conditions, and evaluates how these factors influence nanocarrier design. Furthermore, recent advances in green nanocarrier platforms, AI-assisted formulation strategies, and their potential roles in accelerating research and development are critically assessed. Particular emphasis is placed on current limitations, data availability challenges, regulatory considerations, safety assessment, and translational barriers. By integrating these perspectives, this review provides a comprehensive framework for the future development of sustainable, targeted, and clinically relevant nanocarrier systems for chronic wound therapy.