Tamoxifen encapsulation within polyethylene glycol-coated nanospheres. A new antiestrogen formulation

When dealing with solid tumors in vivo, pegylated long-circulating carrier systems show, after intravenous administration. an attractive extravasation profile with an enhanced localization in the tumoral interstitium. These s ystems could be of help fur the delivery of cancer fighting drugs, such as Tamoxifen, a well known antiestrogen used in breast cancer therapy that pos sesses an extended biodistribution in vivo. This work aimed at encapsulatin g Tamoxifen in long-circulating poly(MePEGcyanoacrylate-co-hexadecylcyanoac rylate) 1:4 nanospheres. Tamoxifen-loaded poly( MePEGcyanoacrylate-co-hexad ecylcyanoacrylate) nanospheres were successfully synthesized and characteri zed in terms of hydrophilicity/hydrophobicity by a model made up From near infrared spectra using principal component analysis. Zeta potential, drug l oading, encapsulation efficiency, as well as biological effect, in vitro re lease and nanospheres integrity were also investigated. Even though near in frared spectroscopy could not detect Tamoxifen, it revealed that Pluronic F 68 was associated with the pegylated nanospheres. HPLC measurements demonst rated that Tamoxifen was encapsulated in the pegylated nanospheres followin g a partition equilibrium between the polymeric and the aqueous phases. The Tamoxifen encapsulated in the nanospheres still showed a transcription inh ibitory activity in ex vivo experiments. However, zeta potential and in vit ro release suggested that Tamoxifen was essentially localized at the nanopa rticles surface, resulting in an important and immediate drug release. (C) 2001 Elsevier Science B.V. All rights reserved.