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Ameliorated delivery of amphotericin B to macrophages using chondroitin sulfate surface-modified liposome
Marium Azim1, Saeed A Khan1, Nashwa Osman2
1Department of Pharmacy, Kohat University of Science and Technology, Kohat, Pakistan.
Background:
The neglected tropical disease leishmaniasis has significant adverse effects from current treatments and limited therapeutic options are currently available.
Objective:
The aim of this study was to develop a surface-modified nano-liposomal drug delivery system, anchored with chondroitin sulfate (CS), to effectively transport Amphotericin B (AmB) to macrophages.
Methods:
Conventional liposome formulations (CL-F) and CS-coated surface-modified liposome formulations (CS-SML-F) were formulated by the thin film hydration method and characterized for particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency with long-term stability. In-vitro drug release using simulation medium, deformability index (DI) by using a polycarbonate membrane, and cell uptake studies among murine macrophages via flow cytometry were analyzed. Scanning and transmission electron microscopy were used to study the surface morphology and shape of the particles.
Results:
Optimized conventional liposome CL-F6, CL-F9 and surface-modified liposomes CS-SML-F6 and CS-SML-F9 exhibited particle size diameters around 280 nm with a PDI of approximately 0.3 over six months of storage at 5 °C, maintaining stable surface charge (circa -30 mV). Sustained drug release peaked between 4 and 12 h and surface morphology showed a uniform distribution of spherical liposome particles. Cell uptake measured by flow cytometry showed the highest rate of macrophage targeting by the CS-SML-Fs.
Conclusion:
These findings have demonstrated that CS surface-modification has enhanced nanoparticle targeting to macrophage binding sites, particularly the cysteine-rich domain, potentially advancing macrophage-targeted drug delivery systems.
