Anticancer drug efficiency is governed by its bioavailability. In order to increase this parameter, we synthesized several
injectable and biodegradable systems based on incorporation of anti-
estrogens (AEs) in nanoparticles (NPs) and
liposomes were synthesized. Both
nanospheres (NS) and
nanocapsules (NCs,
polymers with an oily core in which AEs were solubilized) incorporated high amounts of
4-hydroxy-tamoxifen (4-HT) or
RU 58668 (RU). Physico-chemical and biological parameters of these delivery systems, and coupling of
polyethylene-glycol chains on the NP surface revealed to enhance the anti-tumoral activity of trapped AEs in a
breast cancer MCF-7 cell xenograft model and to induce apoptosis. These features correlated with an augmentation of p21(Waf-1/Cip1) and of p27(Kip1) and a concomitant decrease of
cyclin D1 and E in
tumor extracts.
Liposomes containing various ratios of
lipids enhanced the apoptotic activity of RU in several
multiple myeloma (MM) cell lines tested by flow cytometry. MM cell lines expressed both
estrogen receptor alpha and beta subtypes except Karpas 620. Karpas 620 cells which did not respond to AEs became responsive following ER
cDNA transfection. A new MM xenograft model was generated after s.c. injection of RPMI 8226 cells in nude mice. RU-loaded
liposomes, administered i.v. in this model, at a dose of 12mgRU/kg/week, induced the arrest of
tumor growth contrary to free RU or to empty
liposomes. Thus, the drug delivery of anti-
estrogens enhances their ability to arrest the growth of
tumors which express
estrogen receptors and are of particular interest for
estrogen-dependent
breast cancer treatment. In addition it represents a new potent therapeutic approach for
multiple myeloma.