Tea-Tree Oil-Loaded Core–Shell Chitosan/Polycaprolactone Nanoparticles: In-Vitro Cytotoxicity, Anti-Inflammatory, and Antimicrobial Activities

Multiple drug resistance (MDR) is a persistent issue that requires the development of innovative, beneficial therapeutic agents. Therefore, we aimed at designing a drug delivery formulation of tea-tree oil-loaded polycaprolactone/chitosan core–shell nanoparticles (TTO-loaded PCL/CS NPs) in order to be used as a biologically active nanomaterial. The prepared nanoparticles were optimized and characterized using common characterization techniques such as Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), particle size, and zeta potential (ZP) measurements. Thereafter, the in-vitro effects of the nanoformulation including cytotoxicity, antimicrobial activity, and anti-inflammatory activity were evaluated. Different ratios of the nanoformulation were prepared and characterized; however, the optimum ratio was 2:1 (PCL:CS, w/w) with an average particle size of 10.1 nm, and spherical core–shell NPs were observed. MTT assay results showed that TTO-loaded PCL/CS NPs had the highest cytotoxic activity on BJ cell line (IC₅₀ = 137.3 µg/mL). The TTO nanoformulation demonstrated a strong activity against both Gram-positive and Gram-negative bacteria. Moreover, the nanoformulation showed inhibitory activity against cyclooxygenase-2 enzyme (IC₅₀ = 32.25 µg/mL) with a selectivity index of 1.53, revealing a good anti-inflammatory function. Therefore, TTO-loaded PCL/CS NPs might act as a novel antibacterial candidate for fighting the threat of antibiotic-resistant microorganisms.