Preparation, characterization and evaluation of targeting potential of amphotericin B-loaded engineered PLGA nanoparticles.
OBJECTIVE
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.
Nahar
Manoj
M
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, 470003, India.
Jain
Narendra K
NK
D000666:Amphotericin B / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D019344:Lactic Acid / Q000138:chemical synthesis; D007893:Leishmania donovani / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008358:Mannose / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D053758:Nanoparticles; D010316:Particle Size; D011100:Polyglycolic Acid / Q000138:chemical synthesis; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
D000981:Antiprotozoal Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000666:Amphotericin B; D008358:Mannose