The present work tests the hypothesis that stabilizers have a critical role on nanocarrier stealthiness and anticancer
drug efficacy. Two different types of
docetaxel (Doc)-loaded
nanocapsules (NCs) stabilized with
polysorbate 80 (NC(T80)) and
polyvinyl alcohol (NC(PVA)) were synthesized using the
emulsion solvent diffusion method. These NCs were characterized for particle mean diameter (PMD),
drug content, morphology, surface composition, and degree of crystallinity. Furthermore, the cytotoxicity and cellular uptake of the NCs were investigated in MDA-MB 231 cells, THP-1 monocytes, and THP-1-derived macrophages. The optimized spherical NC(T80) had 123.02 ± 14.6 nm, 0.27 ± 0.1, and 101 ± 37.0% for PMD, polydispersity index, and
drug encapsulation efficiency, respectively. Doc release kinetics from NC(T80) and NC(PVA) mostly provided better fit to zero-order and Higuchi models, respectively.
Powder X-ray diffraction (PXRD) and X-ray photoelectron spectroscopy (XPS) results revealed the presence of amorphous stabilizers on the surface of the NCs. At high
drug concentration, the cytotoxicity of NC(T80) was substantially improved (1.3-1.6-fold) compared with that of NC(PVA) in MDA-MB 231 cells. The uptake of both NCs was inhibited by
latrunculin A and
dynasore, indicating an actin- and
dynamin-dependent endocytosis in MDA-MB 231 cells. This occurred via a multifaceted mechanism involving
clathrin,
caveolin, cytoskeleton, and macropinocytosis. Interestingly, the uptake of NC(PVA) was 2.7-fold greater than that of NC(T80) and occurred through phagocytosis in monocytes and macrophages. This study demonstrates the potential impact of the surface chemistry on the cytotoxicity and phagocytic clearance of nanocarriers for a subsequent improvement of the efficacy of Doc intended for
breast cancer chemotherapy.