title: A Simple and Improved Active Loading Method to Efficiently Encapsulate Staurosporine into Lipid-Based Nanoparticles for Enhanced Therapy of Multidrug Resistant Cancer.
abstract: OBJECTIVE
  This study was aimed at developing a new active loading method to stably encapsulate staurosporine (STS), a water insoluble drug, into lipid-based nanoparticles (LNPs) for drug targeting to tumors.
  
  
  METHODS
  A limited amount of DMSO was included during the active loading process to prevent precipitation and facilitate the loading of insoluble STS into the aqueous core of a LNP. The drug loading kinetics under various conditions was studied and the STS-LNPs were characterized by size, drug-to-lipid ratio, drug release kinetics and in vitro potency. The antitumor efficacy of the STS-LNPs was compared with free STS in a mouse model.
  
  
  RESULTS
  The drug loading efficiency reached 100% within 15 min of incubation at a drug-to-lipid ratio of 0.31 (mol) via an ammonium gradient. STS formed nano-aggregates inside the aqueous core of the LNPs and was stably retained upon storage and in the presence of serum. A 3-fold higher dose of the STS-LNPs could be tolerated by BALB/c mice compared with free STS, leading to nearly complete growth inhibition of a multidrug resistant breast tumor, while free STS only exhibited moderate activity.
  
  
  CONCLUSIONS
  This simple and efficient drug loading method produced a stable LNP formulation for STS that was effective for cancer treatment.
authors.affiliation: Faculty of Pharmaceutical Science, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.|Drug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario, M5G 0A3, Canada.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Tang
authors.affiliation: Faculty of Pharmaceutical Science, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
authors.forename: Weihsu Claire
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Faculty of Pharmaceutical Science, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.|Drug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario, M5G 0A3, Canada.
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Roy
authors.affiliation: Drug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario, M5G 0A3, Canada.
authors.forename: Elijus
authors.initials: E
authors.lastname: Undzys
authors.affiliation: Faculty of Pharmaceutical Science, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada. shyh-dar.li@ubc.ca.|Drug Discovery Program, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario, M5G 0A3, Canada. shyh-dar.li@ubc.ca.
authors.forename: Shyh-Dar
authors.initials: SD
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D019311:Staurosporine / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D008055:Lipids; D008081:Liposomes; D047428:Protein Kinase Inhibitors; D019311:Staurosporine; D004121:Dimethyl Sulfoxide
keywords: Active loading; Liposome; Multidrug resistant cancer; Staurosporine; Water insoluble drug