Noscapine (Nos), an orally available plant-derived
antitussive alkaloid, is in phase II clinical trials for
cancer chemotherapy. It has extensively been shown to inhibit
tumor growth in nude mice bearing human xenografts of hematopoietic, breast, lung, ovarian, brain, and prostate origin. However, high
tumor-suppressive Nos dosages encumber the development of oral
controlled-release formulations because of a short
biological half-life (<2 h), poor absorption, low aqueous solubility, and extensive first-pass metabolism. Here, we present the design, fabrication, optimization, characterization, and
biological evaluation of
estrone-conjugated
noscapine-loaded
gelatin nanoparticles (Nos-ES-GN) for targeting
estrogen-receptor-positive
breast cancer MCF-7 cells.
Gelatin nanoparticles (GN) were a uniformly compact size, stable at physiological pH, and showed a
drug entrapment efficiency of 66.1±5.9 and 65.2±5.6% for Nos-GN and Nos-ES-GN, respectively. The secondary structure of
gelatin nanocoacervates was predicted using circular dichroism and in-silico molecular modeling. Our data suggest that
ethanol-fabricated GN retained the α-helical content of
gelatin, whereas
acetone favored the formation of random coils. The conjugation of
estrone to Nos-GN did not affect the release rate of the
drug, and both formulations followed first-order release kinetics with an initial burst, followed by a slow release. The IC50 value of Nos-ES-GN was 21.2 μmol/l, which was ∼50% lower than the free
drug (43.3 μmol/l), suggesting targeted
drug delivery. Our cell uptake study carried out in an
estrogen-receptor-positive (MCF-7) and negative (MDA-MB-231)
cancer cell lines showed greater accumulation of Nos-ES-GN in MCF-7 cells instead of MDA-MB-231 cells. Our data indicated that
estrone-conjugated nanoparticles may potentially be used for targeting
breast cancer cells.