Optimizing the antimicrobial photodynamic efficacy of curcumin liposomes to treat pulmonary infections caused by gram-positive bacteria.

The current medicine is at a high level of development, facing a global problem. Over the last few decades, the inappropriate use of antibiotics has led to antimicrobial resistance (AMR), where bacteria no longer respond to common antibiotics. To overcome AMR, novel therapy options are required, such as antimicrobial photodynamic therapy (aPDT), initially developed for cancer treatment. In this study, positively charged curcumin (Cur)-loaded 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-3-trimethylammonium-propane (chloride salt) (DOTAP) (Cur-DOTAP) liposomes containing 5 mol% (Cur-DOTAP5) and 10 mol% DOTAP (Cur-DOTAP10) were prepared by varying the Cur:lipid ratio (CL) to investigate the influence on the aPDT efficacy. The CL and the amount of DOTAP do not affect the physicochemical properties of the liposomes, but primarily their structure. Morphological investigation by atomic force microscopy (AFM) confirmed the presence of spherical-shaped unilamellar vesicles (ULVs) for the lowest CL and multilamellar vesicles (MLVs) for higher CLs. This study successfully demonstrated that the CL and the resulting lamellarity of liposomes mainly influence aPDT efficacy. Due to their positive surface charge, liposomes may be absorbed onto the negatively charged bacterial surface through electrostatic interactions, thereby focusing the aPDT action on the cell wall. With an increasing number of layers, Cur is more distributed throughout the layers and presumably less accessible for aPDT in the inner layer, resulting in a maximum reduction in bacterial viability of 3.9 log10.A substantial reduction in the bacterial viability of gram-positive bacteria by more than 5.7 log10 was determined for ULVs only, independent of the amount of DOTAP. Due to their structure, the cell wall of gram-negative bacteria is a non-accessible barrier for the Cur-DOTAP liposomes. Gram-positive bacteria are often responsible for lung infections. To address the pulmonary tissue, nebulization stability was characterized. The biocompatibility of the liposomes was confirmed in vitro with mouse connective tissue fibroblasts (L929) and in ovo using the chorioallantoic membrane (CAM) model, proving the liposomes' suitability for pulmonary application. Positively charged Cur-DOTAP liposomes offer a promising approach to addressing lung infections caused by gram-positive bacteria.