Preparation, characterization and evaluation of targeting potential of amphotericin B-loaded engineered PLGA nanoparticles.

Purpose: The objective of present work was to develop a mannose-anchored, engineered nanoparticulate system for efficient delivery of amphotericin B to macrophages. Furthermore, the effect of spacer on macrophage targeting was also evaluated.

Methods: PLGA was conjugated to mannose via direct coupling (M-PLGA) and via PEG spacer (M-PEG-PLGA), and engineered PLGA nanoparticles (M-PNPs and M-PEG-PNPs) were prepared from respective conjugates. These prepared engineered PNPs were characterized for size, polydispersity index (PDI), surface charge, and drug entrapment efficiency (% DEE). Transmission electron microscopy (TEM) and atomic force microscopy (AFM) were employed to study the shape and surface morphology of engineered PNPs. Macrophage targeting was evaluated via cellular uptake, ex vivo antileishmanial activity and in vivo biodisposition pattern of engineered PNPs in macrophage-rich organs.

Results: The developed engineered PNPs were found to be of nanometric size (<200 nm) and to have low PDI (<0.162) and good entrapment efficiency (%DEE >53.0%). AFM and TEM revealed that both M-PNPs and M-PEG-PNPs had smooth surface and spherical topography. Engineered PNPs with spacer showed enhanced uptake, potential antileishmanial activity and higher disposition in macrophage-rich organs, suggesting improved macrophage targeting.

Conclusions: The results suggest that engineering of nanoparticles could lead to development of efficient carrier for macrophage targeting.