Curcumin-cyclodextrin inclusion complexes embedded in intrinsically active nano-assemblies: Preparation, characterization, antibacterial and antibiofilm activity against ESKAPE pathogens

Curcumin loaded β-CD inclusion complexes (CCDs) embedded in intrinsically active rhamnosomes (CCDRs) were developed as alternative antimicrobials at the nano-scale to control ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. The physicochemical analysis of CCDRs demonstrated that the addition of glycolipids (rhamnolipids) during the development of liposomes (phospholipids based) provided stability while the average size (158±5 nm) and polydispersity index (PDI) values of 0.2 demonstrated homogenous population of rhamnosomes. The incorporation of rhamnolipids with phospholipids increased the zeta potential to -45±1 mV with 76±1 % encapsulation efficiency for curcumin with enhanced photochemical and storage stability. In vitro, release studies demonstrated sustained release of curcumin due to its incorporation in β-CD molecular buckets, which were loaded in the aqueous liposomal core. These CCDRs with intrinsic antibacterial and antibiofilm potential enhanced the antimicrobial spectrum against ESKAPE pathogens demonstrating synergism between curcumin and rhamnolipids, by targeting multiple sites of bacterial cells and biofilms as compared to conventional antibiotics. Our study outlines that rhamnolipids and curcumin loaded inclusion complexes together offer an exciting potential for functionalized liposomal delivery systems that would be promising for the development of effective alternative therapeutics against ESKAPE pathogens.