Nanosomal formulation of a vitamin D receptor alkylating compound for prostate cancer
R. Ray and T. Castor
Boston University School of Medicine, US
vitamin D derivative, nanosomal formulation, receptor-targeted drug, prostate cancer
An inverse relationship between incidence and mortality from various cancers and dietary vitamin D is well-established. Furthermore, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the vitamin D hormone has strong antiproliferative effects in cancer cells. But it is highly toxic in therapeutic doses. In vitro tests of 1,25-dihydroxyvitamin D3-3-bromoacetate (1,25(OH)2D3-3-BE), a derivative of 1,25(OH)2D3 designed and selectively targeted to have increased antiproliferative effect while reducing systemic toxicity through alkylation of the ligand-binding domain of vitamin D receptor in tumor cells, have demonstrated that this compound has strong growth-inhibitory and apoptosis-inducing properties in hormone-sensitive and hormone-insensitive prostate cancer cells, significantly stronger than 1,25(OH)2D3. Furthermore, preliminary in vivo studies showed that 1,25(OH)2D3-3-BE is of low-toxicity, and it strongly reduces androgen-refractory prostate tumor in a mouse xenograft model. Phospholipid nanosomes are small, uniform liposomes that are made up of biocompatible phospholipids and cholesterol; and they are designed to encapsulate vitamin D drugs in the lipid-bilayer of the nansomes. Nanosomal formulation of 1,25(OH)2D3-3-BE is designed to further reduce systemic toxicity, increase circulatory half-life and efficacy resulting in an improved therapeutic index for this vitamin D–based drug in prostate cancer.
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Nanotech 2007 Conference Program Abstract