Camptothecin (CPT) is a potent DNA Topoisomerase I inhibitor with anti-tumor activity in hematological and solid tumors.
However, it did not reach clinical use because of its poor solubility and high degrability. β-Cyclodextrin nanosponge (CN) have been demonstrated to be able to increase the solubility of lipophilic compounds and to protect them from degradation. In the present study, we evaluated whether β-Cyclodextrin nanosponge carriers can overcome CPT chemical disadvantages and improve the in vitro anti-tumor efficacy in the androgen refractory models of prostate cancer DU145 and PC-3 and the androgen sensitive model LNCaP. Camptothecin-loaded β-Cyclodextrin nanosponge (CN-CPT) showed sizes of about 400nm, spherical shape and a drug loading of 38%. HPLC analysis, performed on the cell pellet after treatment with CN-CPT revealed that CPT concentration increased over time indicating a prolonged release of the drug. Moreover, CN-CPT inhibited Topoisomerase I activity, and induced DNA damage, and cell cycle arrest more effectively than CPT, indicating that the CN-CPT formulation does not affect activity of the drug. Moreover, Annexin V/Propidium Iodide staining showed an induction of cell death at low concentrations that were not effective for CTP. LNCaP cells were less sensitive to CPT than PC-3 and DU145 cells, but CN-CPT still exerted higher anti-proliferative activity and DNA damage ability than CPT. The experiments performed in LNCaP cells demonstrated that CN-CPT treatment inhibited expression of the androgen receptor at doses where CPT was ineffective. Our results demonstrated the higher anti-tumor effectiveness of CN-CPT compare to CPT in prostate cancer cells, supporting the relevance of future studies for the use of the β-Cyclodextrin nanosponge to deliver anticancer drugs in vivo.
Written by:
Minelli R, Cavalli R, Ellis L, Pettazzoni P, Trotta F, Ciamporcero E, Barrera G, Fantozzi R, Dianzani C, Pili R. Are you the author?
Department of Drug Science and Technology, University of Turin, Via P. Giuria 9, 10125 Turin, Italy; Genitourinary Program, Roswell Park Cancer Institute, Elm & Carlton Streets, 14263 Buffalo, NY, USA.
Reference: Eur J Pharm Sci. 2012 Aug 15;47(4):686-694.
doi: 10.1016/j.ejps.2012.08.003
PubMed Abstract
PMID: 22917641
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