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Enhanced Percutaneous Delivery of 1,1-bis(3 -indolyl)-1-(p-chlorophenyl) Methane for Skin Cancer Chemoprevention

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Skin cancer has high incidence in the United States and is mainly caused by ultraviolet B (UVB) radiation. In this study, we demonstrated the role of 1,1-bis(3′-indolyl)-1-(p-chlorophenyl) methane (DIM-D) in the prevention of skin photocarcinogenesis using an in vivo UVB-induced skin cancer model. We also evaluated the efficiency of oleic acid-modified nanostructured lipid carriers to deliver DIM-D across the skin barrier into the epidermis for chemopreventive activity. Nanocarriers were 203.00 ± 21.21 nm in diameter with polydispersity, zeta potential and entrapment efficiency of 0.33 ± 0.01, 37.17 ± 0.90 mV and 93.64 ± 0.65%, respectively. Oleic acid-modified nanocarriers were incorporated into Hydroxypropyl methylcellulose to form DIM-D-Nanogel (DIM-D-N). DIM-D-N pretreatment prior to UVB exposure delayed tumor initiation and reduced tumor multiplicity (p < 0.05) at the end of the study compared to Epigallocatechin gallate (EGCG) gel pretreatment. DIM-D-N pretreatment decreased UVB-induced damage to skin lipids and proteins (p < 0.05), respectively by 7.63 and 2.56-fold less than EGCG gel pretreatment and by 17.86 and 11.92-fold less than UVB-only treatment. Histology showed rete-ridge extension, epidermal thickening and hyperkeratosis for UVB-only treatment and EGCG gel pretreatment; DIM-D-N pretreatment showed similar features as the negative control. Western blot analysis showed increased Nurr1 expression (p < 0.05) for DIM-D-N pretreated group compared to EGCG gel (4.68-fold). DIM-D-N pretreatment reduced BCl-2 expression (p < 0.05) but increased Bax and cPARP. Knock down studies with Nurr1 siRNA reduced the expressions of Nurr1 and cPARP by 8.18 and 1.45-fold, respectively (p < 0.05). Our results suggest the role of DIM-D in skin cancer chemoprevention mediated by possible molecular therapeutic targets such as Nurr1.
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Keywords: 1,1-BIS(′3-INDOLYL)-1-(P-CHLOROPHENYL) METHANE (DIM-D); 3,3′-DIINDOLYLMETHANE (DIM); DIM-D NANOGEL (DIM-D-N); EPIGALLOCATECHIN GALLATE (EGCG); GLUTATHIONE DEPLETION; LIPID PEROXIDATION; NANOSTRUCTURED LIPID CARRIERS (NLC); OLEIC ACID SURFACE MODIFIED NLC (NLC-OA); PROTEIN CARBONYLATION; SKIN CANCER CHEMOPREVENTION; ULTRAVIOLET B (UVB) RADIATION

Document Type: Research Article

Publication date: July 1, 2015

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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