Alkaloid-based nanodrug delivery systems: An emerging strategy against drug-resistant bacterial wound infections

Bacterial infections significantly impede wound healing. With the escalating crisis of antimicrobial resistance, conventional antibiotics increasingly fail to meet the clinical demands for treating wounds infected with resistant strains. Plant-derived alkaloids have emerged as promising alternatives, exhibiting potent antibacterial activity, a low propensity for inducing resistance, and synergistic effects when combined with traditional antibiotics. Furthermore, they accelerate wound repair through anti-inflammatory and antioxidant mechanisms, while stimulating skin fibroblast proliferation. Despite these advantages, the clinical translation of most alkaloids is severely hindered by their low aqueous solubility and poor bioavailability. Nanodrug delivery systems (NDDS) offer a robust solution to overcome these pharmacokinetic limitations. Beyond significantly improving the targeted delivery and bioavailability of poorly soluble drugs, specific functionalized NDDS can synergistically amplify the inherent antibacterial and tissue-repairing properties of alkaloids. This review systematically evaluates the therapeutic potential and current limitations of both alkaloid monomers and alkaloid-based NDDS in infected wound management, aiming to provide a comprehensive reference for future research and clinical translation.