Enhanced antitubercular activity, alveolar deposition and macrophages uptake of mannosylated stable nanoliposomes

Abstract

Two targets were set for the current work: exploiting the effect of the targeting ligand 4-aminophenyl-alpha-D–manno-pyranoside (PAM) in enhancing the uptake of nanoliposomes (NL) by alveolar macrophages and investigating the efficiency of NL co-spray drying with the carrier biomacromolecule dextran (DX) for improved physical stability and lung deposition. Moxifloxacin (MXF) loaded NL were prepared by reversed phase evaporation method using different lipids and the surface of selected NL was decorated with PAM. Selected NL formulations were co-spray dried with dextran (DX) to yield surface modified NL embedded in microparticles (SD-NLEM). Using the proportion method, the antibacterial activity against resistant M. tuberculosis was tested. The safety of the developed system was tested on lung cancer cells and the uptake by alveolar macrophages was followed using flow cytometry measurements. Fluorescently labeled NL were tracked in vivo in rats to test lung deposition following pulmonary administration. The results showed that spray drying efficiently enhanced the stability and morphological characteristics of the optimized monodisperse NL achieving a respirable particle fraction of more than 75%. Deep lung deposition was confirmed in rats. Charged NL provided higher anti-tubercular activity and macrophage uptake compared to the neutral ones. Mannosylation efficiently increased active uptake by alveolar macrophages uptake.