Juniperus phoenicea extract-loaded nanostructured lipid carriers for potent antimicrobial and anticancer combination therapy

Abstract This study evaluates the antimicrobial properties of Juniperus phoenicea L. against multidrug-resistant microbes, highlighting potential synergistic effects of combining the J. phoenicea L. newly synthesized nanoparticles with conventional antibiotics and anticancer agents. Juniperus phoenicea L. ethanolic and ethyl acetate extracts were prepared. Antibacterial activity against a panel of multidrug-resistant microbes showed the ethanolic extract as superior to the ethyl acetate extract, with Acinetobacter baumannii being the most susceptible organism (minimum inhibitory MIC = 12.5 µg/mL). Phytochemical profiling of the ethanolic extract revealed predominant components, namely: Apigenin-7-glucoside, α-pinene, and Cedrol. Network pharmacology-based analysis suggested the potent effect of these compounds as anticancer and antibacterial agents. J. phoenicea L. nanoparticles were synthesized by a combined hot-melt dispersion and homogenization approach. Characterization yielded a zeta vesicle size of 98.6 nm, PDI 0.23, zeta potential + 48.5 mV, EE% 92.4%, and TEM size 76.2 nm. The nanoparticles markedly enhanced antibacterial activity (MIC = 6.25 µg/mL) with complete eradication of A. baumannii after 16 h. The combination with Amoxicillin and Cefoxitin showed synergistic effects. In anticancer assays, nanoparticles outperformed Fluorouracil, with IC 50 = 9.05 ± 0.49 µg/mL (≈ 8.7-fold higher anticancer potency than the crude extract). The Fluorouracil–nanoparticle combination further reduced IC 50 to 6.12 ± 0.41 µg/mL. Hence, it was concluded that J. phoenicea L. ethanolic extract exhibits potent antibacterial and anticancer properties and provides an effective nanoparticle precursor. Synergistic interactions with antibiotics and Fluorouracil suggest a multifaceted therapeutic strategy against infections and cancer, meriting further in vivo studies and mechanistic exploration.