This study was carried out to evaluate and compare the biodistribution profile of
tamoxifen when administered intravenously (i.v.) as a simple
solution or when encapsulated in polymeric nanoparticulate formulations, with or without surface-
stabilizing agents.
Tamoxifen-loaded, poly(
ethylene oxide)-modified
poly(epsilon-caprolactone) (
PEO-PCL) nanoparticles were prepared by
solvent displacement process that allowed in situ surface modification via physical adsorption of
poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (
PEO-PPO-PEO) triblock polymeric stabilizer (
Pluronic). The nanoparticles were characterized for particle size and surface charge. Presence of PEO chains on nanoparticle surface was ascertained by electron spectroscopy for chemical analysis (ESCA). In vivo biodistribution studies were carried out in Nu/Nu athymic mice bearing a human
breast carcinoma xenograft, MDA-MB-231 using tritiated [(3)H]-
tamoxifen as radio-marker for quantification.
PEO-PCL nanoparticles with an average diameter of 150-250 nm, having a smooth spherical shape, and a positive surface charge were obtained with the formulation procedure. About 90%
drug encapsulation efficiency was achieved when
tamoxifen was loaded
at 10% by weight of the
polymer. Aqueous wettability, suspendability, and ESCA results showed surface hydrophilization of the PCL nanoparticles by the
Pluronics. The primary site of accumulation for the
drug-loaded nanoparticles after i.v. administration was the liver, though up to 26% of the total activity could be recovered in
tumor at 6h post-injection for PEO-modified nanoparticles.
PEO-PCL nanoparticles exhibited significantly increased level of accumulation of the
drug within
tumor with time as well as extended their presence in the systemic circulation than the controls (unmodified nanoparticles or the
solution form).
Pluronic surfactants (F-68 and F-108) presented simple means for efficient surface modification and stabilization of PCL nanoparticles to achieve preferential
tumor-targeting and a circulating
drug reservoir for
tamoxifen.