title: Parenterally administrable nano-micelles of 3,4-difluorobenzylidene curcumin for treating pancreatic cancer.
abstract: Pancreatic cancer remains one of the most devastating diseases in terms of patient mortality rates for which current treatment options are very limited. 3,4-Difluorobenzylidene curcumin (CDF) is a nontoxic analog of curcumin (CMN) developed in our laboratory, which exhibits extended circulation half-life, while maintaining high anticancer activity and improved pancreas specific accumulation in vivo, compared with CMN. CDF however has poor aqueous solubility and its dose escalation for systemic administration remains challenging. We have engineered self-assembling nano-micelles of amphiphilic styrene-maleic acid copolymer (SMA) with CDF by non-covalent hydrophobic interactions. The SMA-CDF nano-micelles were characterized for size, charge, drug loading, release, serum stability, and in vitro anticancer activity. The SMA-CDF nano-micelles exhibited tunable CDF loading from 5 to 15% with excellent aqueous solubility, stability, favorable hemocompatibility and sustained drug release characteristics. The outcome of cytotoxicity testing of SMA-CDF nano-micelles on MiaPaCa-2 and AsPC-1 pancreatic cancer cell lines revealed pronounced antitumor response due to efficient intracellular trafficking of the drug loaded nano-micelles. Additionally, the nano-micelles are administrable via the systemic route for future in vivo studies and clinical translation. The currently developed SMA based nano-micelles thus portend to be a versatile carrier for dose escalation and targeted delivery of CDF, with enhanced therapeutic margin and safety.
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48201, USA.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kesharwani
authors.affiliation: Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, 740 HWCRC, Detroit, MI 48201, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Interdisciplinary Science & Technology Research Academy, Department of Chemistry, Abeda Inamdar College, University of Pune, Azam Campus, Pune 411001, India.
authors.forename: Subhash
authors.initials: S
authors.lastname: Padhye
authors.affiliation: Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, 740 HWCRC, Detroit, MI 48201, USA.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48201, USA. Electronic address: akiyer@wayne.edu.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Iyer
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D036381:Diarylheptanoids; D006801:Humans; D008823:Micelles; D036103:Nanotechnology; D010190:Pancreatic Neoplasms / Q000188:drug therapy*
chemical_list: C000611228:3,4-difluorobenzylidenecurcumin; D000970:Antineoplastic Agents; D036381:Diarylheptanoids; D008823:Micelles; D003474:Curcumin
keywords: 3,4-Difluorobenzylidene curcumin; Aqueous solubility; Nano-micelles; Nanoparticles; Pancreatic cancer; Styrene-maleic acid copolymer