Nanostructured lipid carriers for enhanced oral bioavailability and antibacterial efficacy of curcumin against multidrug-resistant pathogens

Background: Poor solubility and limited oral bioavailability restrict the clinical translation of curcumin despite its well-documented antibacterial and anti-inflammatory activity. Nanostructured lipid carriers (NLCs) offer a promising strategy to overcome these barriers by improving stability, gastrointestinal absorption, and therapeutic delivery.

Methods: Curcumin-loaded NLCs were prepared using hot homogenization and ultrasonication, with glyceryl monostearate as solid lipid and oleic acid as liquid lipid. Particle size, zeta potential, and entrapment efficiency were determined by dynamic light scattering and HPLC. In vitro release was studied under simulated gastric and intestinal conditions. Antibacterial activity was tested against MDR Staphylococcus aureus and Escherichia coli using MIC/MBC assays and biofilm inhibition models. Pharmacokinetic studies were conducted in Wistar rats following oral administration.

Results: Optimized curcumin-NLCs exhibited a mean particle size of 121 ± 8 nm, zeta potential of −32 mV, and entrapment efficiency of 89%. Controlled release demonstrated sustained drug release over 24 h. Antibacterial assays revealed significant improvement in potency, with MIC values reduced fourfold compared to free curcumin. Biofilm inhibition reached 73% at sub-MIC concentrations. Pharmacokinetic analysis showed a 5.2-fold increase in oral bioavailability, with peak plasma concentrations achieved at 3 h post-administration.

Conclusion: Curcumin-loaded NLCs significantly enhance oral bioavailability and antibacterial efficacy, representing a robust drug delivery platform for repositioning natural compounds against multidrug-resistant infections. These findings highlight the potential of lipid nanocarriers in medicinal chemistry and pharmaceutics for developing next-generation therapeutic formulations.