Thymoquinone-Loaded Nanocarriers: A Promising Phytochemical Engineered for Tackling Antimicrobial Resistance and Challenging Infections, a Systematic Scoping Review of Preclinical Studies

Thymoquinone (TQ), a bioactive compound derived from Nigella sativa herbal plant, exhibits antioxidative, anti-inflammatory, and antimicrobial effects against various bacteria, viruses, fungi, protozoa, and flatworms. A systematic search was conducted across Embase, PubMed, Scopus, and Web of Science until January 2025. All preclinical studies discussing the bactericidal, virucidal, fungicidal, and parasiticidal effects of nano-based formulations of N. sativa/TQ were included. Overall, 148 studies—comprising in vitro, in vivo, ex vivo, and in silico research—were identified involving 185 unique N. sativa/TQ-loaded nanocarriers with antimicrobial properties. The predominant nanoencapsulation methods included inorganic nanoparticles (27%), nanocomposites (23.2%), and nanofibers (13.5%). The essential oil (27.6%) and aqueous extract (20.5%) of the seeds, along with TQ (22.2%), were the most common natural cargos. 149 nanoformulations showed effectiveness against bacteria, 42 against fungi, 8 against viruses, and 7 against parasites. Additionally, 29 nanoformulations showed antibiofilm properties, and 41 showed efficacy against multidrug-resistant pathogens. Only 18 nanoformulations were not effective against at least one tested pathogen. 91.9% of the tested nanoformulations against Staphylococcus aureus showed effectiveness, while this percentage for Escherichia coli and Candida albicans was 88.5% and 96.9%, respectively. These three were the most widely examined pathogens in preclinical studies. The proposed clinical and practical applications were most prominent in wound healing (42 nanoformulations), followed by food preservation (33 nanoformulations) and water purification (9 nanoformulations). Integrating nano-based drug delivery systems with the antimicrobial benefits of TQ can address TQ’s limitations, including instability and low oral bioavailability. This review identifies knowledge gaps regarding TQ nanomedicines and emphasizes the need for regulatory frameworks for safety and clinical applicability, thereby facilitating their progression into human clinical trials.