title: Albumin-coated nanocrystals for carrier-free delivery of paclitaxel.
abstract: Nanoparticles are used to deliver anticancer drugs to solid tumors. However, clinical development of nanoparticles is challenging because of their limitations in physicochemical properties, such as low drug loading efficiency and poor circulation stability. Low drug loading not only causes technical difficulty in administration but also increases the amount of co-delivered carrier materials, imposing biological burdens to patients. Poor circulation stability causes loss of pharmacokinetics benefits of nanoparticles. To overcome these challenges, we developed an albumin-coated nanocrystal (NC) formulation of paclitaxel (PTX) with 90% drug loading and high serum stability. The NC was produced by inducing crystallization of PTX in aqueous medium, coating the surface with albumin, and removing extra non-drug ingredients. Among three types of NC produced with different crystallization conditions, NC crystallized in the medium containing Pluronic F-127 then coated with albumin ("Cim-F-alb") had the smallest size and the most native albumin, thus showing the most favorable cell interaction profiles (low uptake by J774A.1 macrophages and high uptake by SPARC+B16F10 melanoma cells). Cim-F-alb remained more stable in undiluted serum than Abraxane, a commercial albumin-based PTX nanoparticle formulation, while maintaining comparable cytotoxicity to those of Abraxane and solvent-dissolved PTX. In a mouse model of B16F10 melanoma, Cim-F-alb showed higher antitumor efficacy than Abraxane at the same dose. This study demonstrates the feasibility and benefits of delivering an anticancer drug using a carrier-free nanoparticle formulation with good circulation stability.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette 47907, USA.
authors.forename: Joonyoung
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette 47907, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette 47907, USA. Electronic address: yyeo@purdue.edu.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D012709:Serum Albumin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012709:Serum Albumin; D017239:Paclitaxel
keywords: Abraxane; Albumin; Anti-tumor efficacy; Carrier-free; Drug delivery; Nanocrystals; Paclitaxel