title: Synthesis and characterization of folate decorated albumin bio-conjugate nanoparticles loaded with a synthetic curcumin difluorinated analogue.
abstract: Albumin-bound paclitaxel colloidal nanoparticle (Abraxane®) is an FDA approved anticancer formulation available in the market. It is a suspension which is currently used therapeutically for treating cancers of the breast, lung, and pancreas among others. CDF is a novel new and potent synthetic curcumin analogue that is widely used for breast and ovarian cancer. The aim of this study was to use biocompatible albumin as well as folate decorated albumin to formulate colloidal nanoparticles encapsulating curcumin difluorinated (CDF). CDF has demonstrated a 16-fold improvement in stability and remarkable anticancer potency compared to its natural derivative, curcumin. CDF showed marked inhibition of cancer cell growth through down-regulation of multiple miRNAs, up-regulation of phosphatase and tensin homolog (PTEN), and attenuation of histone methyl transferase EZH2. However, CDF is highly hydrophobic and photodegradable with sparing aqueous solubility. In this study, we have formulated albumin nanoparticle using a modified desolvation method, which yielded high CDF loading in a nanoformulation. The physicochemical properties of CDF loaded albumin and folate-decorated albumin nanosuspensions were assessed for particle size, morphology, zeta potential, drug encapsulation efficiency/loading, solubility and drug release. Importantly, the folate ligand decorated albumin nanoparticles were formulated in principle to passively and actively target folate-overexpressing-cancers. In this study, the synthesis and optimization of BSA and folate decorated BSA conjugated CDF nanoparticles are assessed in detail that will be useful for its future clinical translation.
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Kaustubh A
authors.initials: KA
authors.lastname: Gawde
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kesharwani
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Samaresh
authors.initials: S
authors.lastname: Sau
authors.affiliation: Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.affiliation: Interdisciplinary Science & Technology Research Academy, Department of Chemistry, Abeda Inamdar College, Azam Campus, University of Pune, Pune 411001, India.
authors.forename: Subhash
authors.initials: S
authors.lastname: Padhye
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA; Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar, MP, India.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Kashaw
authors.affiliation: Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA; Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI 48201, USA. Electronic address: arun.iyer@wayne.edu.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Iyer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical; D003102:Colloids; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry*; D004337:Drug Carriers; D065546:Drug Liberation; D004355:Drug Stability; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry*; D009994:Osmolar Concentration; D010316:Particle Size; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D003102:Colloids; D004337:Drug Carriers; D012710:Serum Albumin, Bovine; D005492:Folic Acid; D003474:Curcumin
keywords: Albumin bio-conjugates; BSA nanoparticles; CDF; Colloidal nanoparticles; Folate targeting; Folate-BSA conjugate; Protein conjugates