The study evaluates the capability of
tripalmitin nanoparticles in enhancing the
tumor uptake of
etoposide, and the influence of administration route on the biodistribution and
tumor uptake of
etoposide loaded
tripalmitin (ETPL) nanoparticles in Dalton's
lymphoma tumor bearing mice. ETPL nanoparticles were prepared by melt-emulsification and high pressure homogenization followed by the spray drying of nanodispersion. Characterization of the nanoparticles was done by particle size analysis, zeta potential measurement and scanning electron microscopy. The size of ETPL nanoparticles was 387 nm and possessed negative charge.
Etoposide and ETPL nanoparticles were radiolabeled with 99mTc with high labeling efficiency. The labeled complexes showed good in vitro stability in the presence of
DTPA/
cysteine and serum stability.
Etoposide and ETPL nanoparticles were injected by subcutaneous, intravenous or intraperitoneal routes and their biodistribution and
tumor uptake were determined.
Subcutaneous injection reduced the distribution of ETPL nanoparticles to all the tissues studied whereas after
intraperitoneal injection, the distribution of ETPL nanoparticles to tissues was higher than free
etoposide. The
intravenous injection resulted in lower concentrations of ETPL nanoparticles in the organs of RES compared to free
etoposide. ETPL nanoparticles experienced significantly high brain distribution after
intraperitoneal injection indicating its potential use in targeting
etoposide to
brain tumors. After
subcutaneous injection, the tissue distribution of ETPL nanoparticles increased with time indicating their accumulation at the injection site for a longer time. The
tumor uptake of both
etoposide and ETPL nanoparticles was significantly high after
subcutaneous injection (P<0.001) compared to the other routes of administration. The
tumor concentration of ETPL nanoparticles after
subcutaneous injection was 59 folds higher than that obtained after intravenous and 8 folds higher than after intraperitoneal route at 24 h post-injection. The
tumor concentration of ETPL nanoparticles increased with time after
subcutaneous injection indicating the slower and progressive penetration from the injection site into the
tumor. The study signifies the advantage of incorporating
etoposide into
tripalmitin nanoparticles in controlling its biodistribution and enhancing the
tumor uptake by several folds. The study also reveals that, of the three routes investigated,
subcutaneous injection is the route of preference for facilitating high
tumor uptake and retention and is likely to have greater antitumor effect resulting in
tumor regression.