title: Formulation development of a novel targeted theranostic nanoemulsion of docetaxel to overcome multidrug resistance in ovarian cancer.
abstract: OBJECTIVE
  Ovarian cancer is a highly lethal disease in which the majority of patients eventually demonstrate multidrug resistance. Develop a novel active targeted theranostic nanomedicine designed to overcome drug efflux mechanisms, using a Generally Regarded As Safe (GRAS) grade nanoemulsion (NE) as a clinically relevant platform.
  
  
  METHODS
  The NEs surface-functionalized with folate and gadolinium, were made using GRAS grade excipients and a high-shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3 and SKOV3TR. The NE accumulation in tumors was evaluated in SKOV3 tumor-bearing mice by magnetic resonance imaging (MRI).
  
  
  CONCLUSIONS
  The NE with particle size < 150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and folate-targeted NEs; improved cytotoxicity was observed for the folate-targeted NEs showing a 270-fold drop in the IC50 in SKOV3TR cells as compared to docetaxel alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist®. Folate-targeted NEs accumulated in tumors for prolonged period of time compared to Magnevist® and showed enhanced contrast compared to non-targeted NEs with MRI in SKOV3 tumor-bearing mice suggesting active targeting of NEs due to folate modification.
  
  
  CONCLUSIONS
  A folate-targeted, theranostic NE delivers docetaxel by receptor mediated endocytosis that shows enhanced cytotoxicity capable of overcoming ABC transporter mediated taxane resistance. The diagnostic capability of the targeted nanomedicine showed enhanced contrast in tumors compared to clinically relevant MRI contrast agent Magnevist®.
authors.affiliation: a Nemucore Medical Innovations, Inc. , Worcester , MA , USA .
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ganta
authors.affiliation: b Department of Pharmaceutical Sciences , School of Pharmacy, Northeastern University , Boston , MA , USA .
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.affiliation: c Blue Ocean Biomanufacturing, Inc. , Worcester , MA , USA .
authors.forename: Yashesh
authors.initials: Y
authors.lastname: Rawal
authors.affiliation: a Nemucore Medical Innovations, Inc. , Worcester , MA , USA .|c Blue Ocean Biomanufacturing, Inc. , Worcester , MA , USA .
authors.forename: Joseph
authors.initials: J
authors.lastname: Cacaccio
authors.affiliation: a Nemucore Medical Innovations, Inc. , Worcester , MA , USA .
authors.forename: Niravkumar R
authors.initials: NR
authors.lastname: Patel
authors.affiliation: d Center for Translational Imaging, Northeastern University , Boston , MA , USA .|e Center for Translational Cancer Nanomedicine Northeastern University , Boston , MA , USA , and.
authors.forename: Praveen
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: d Center for Translational Imaging, Northeastern University , Boston , MA , USA .|e Center for Translational Cancer Nanomedicine Northeastern University , Boston , MA , USA , and.
authors.forename: Craig F
authors.initials: CF
authors.lastname: Ferris
authors.affiliation: b Department of Pharmaceutical Sciences , School of Pharmacy, Northeastern University , Boston , MA , USA .|e Center for Translational Cancer Nanomedicine Northeastern University , Boston , MA , USA , and.
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
authors.affiliation: a Nemucore Medical Innovations, Inc. , Worcester , MA , USA .|c Blue Ocean Biomanufacturing, Inc. , Worcester , MA , USA .|e Center for Translational Cancer Nanomedicine Northeastern University , Boston , MA , USA , and.|f Foundation for the Advancement of Personalized Medicine Manufacturing , Phoenix , AZ , USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Coleman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D004655:Emulsions / Q000737:chemistry*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000737:chemistry; D005682:Gadolinium / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry*; D000068936:Theranostic Nanomedicine
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D004337:Drug Carriers; D004655:Emulsions; D043823:Taxoids; D000077143:Docetaxel; C080625:taxane; D005492:Folic Acid; D005682:Gadolinium
keywords: Docetaxel; MRI; folate; gadolinium