چکیده (انگلیسی):

Purpose. To develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl
monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel.
Methods. Chitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation
methods. Particle size and surface charge were determined. The morphological characteristics and
cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug
loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC
methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells
(MDA-MB-231).
Results. These studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized
particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment
efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The
nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive
charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of
mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC50 of
PTX.
Conclusion. These advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably
minimizing the adverse side effects.