title: Nanoemulsion based concomitant delivery of curcumin and etoposide: impact on cross talk between prostate cancer cells and osteoblast during metastasis.
abstract: An attempt has been made to use curcumin (CUR) in combination with Etoposide (ETP) by encapsulating in nanoemulsion, as two tier approach i.e., to evaluate improvement in efficacy of ETP on prostate cancer cells (PC3 and DU145) and to assess their effect on cross-talk between osteoblast and tumor cells leading to metastatic cascade in bones. Nanoemulsion was developed and evaluated for size, charge, in-vitro drug release and anticancer activity, effect on cross talk between osteoblast and prostate cancer cells and pharmacokinetics in rats. The entrapment efficiency of both ETP and CUR in nanoemulsion was more than 98% while the globule size was less than 150 nm with zeta potential - 29.8 mV. The percent inhibition in case of ETP and ETP: CUR (1:3 w/w) was 55.92 ± 1.2 and 41.13 ± 2.4% (at 5 μM) respectively when tested in PC3 cells. DU-145 seemed to be less responsive in comparison to PC3 cells both in respect of ETP and their mixture (ETP+ CUR). Our data shows that CUR and ETP after encapsulation in nanoemulsion (F5) were effectively delivered intracellularly in PC3 cells and the cytotoxicity of F5 was enhanced by 1.5 fold as compared to ETP + CUR at 5 μM concentration. It has also been observed that mice calvarial osteoblasts cultured and incubated with PC-3 and DU-145 cells conditioned media induces inhibition of osteoblast differentiation event. While this inhibition was significantly reversed by F5 at 5 μM concentration over other treated groups, the pharmacokinetic profile of both ETP and CUR was also significantly improved when administered in nanoemulsion.
authors.forename: Prashant
authors.initials: P
authors.lastname: Shukla
authors.forename: Vineet
authors.initials: V
authors.lastname: Mathur
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Vikram
authors.initials: V
authors.lastname: Khedgikar
authors.forename: Venkatesh B
authors.initials: VB
authors.lastname: Teja
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Chaudhary
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kushwaha
authors.forename: Himangsu K
authors.initials: HK
authors.lastname: Bora
authors.forename: Rituraj
authors.initials: R
authors.lastname: Konwar
authors.forename: Ritu
authors.initials: R
authors.lastname: Trivedi
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D002450:Cell Communication / Q000187:drug effects*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage; D004338:Drug Combinations; D004655:Emulsions; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D004655:Emulsions; D053769:Nanocapsules; D005047:Etoposide; D003474:Curcumin