title: Optimization of doxorubicin loading for superabsorbent polymer microspheres: in vitro analysis.
abstract: OBJECTIVE
  This study was designed to establish the ability of super-absorbent polymer microspheres (SAP) to actively uptake doxorubicin and to establish the proof of principle of SAP's ability to phase transfer doxorubicin onto the polymer matrix and to elute into buffer with a loading method that optimizes physical handling and elution characteristics.
  
  
  METHODS
  Phase I: 50-100 μm SAP subject to various prehydration methods (normal saline 10 cc, hypertonic saline 4 cc, iodinated contrast 10 cc) or left in their dry state, and combined with 50 mg of clinical grade lyophilized doxorubicin reconstituted with various methods (normal saline 10 cc and 25 cc, sterile water 4 cc, iodinated contrast 5 cc) were placed in buffer and assessed based on loading, handling, and elution utilizing high-performance liquid chromatography (HPLC). Phase II: top two performing methods were subject to loading of doxorubicin (50, 75, 100 mg) in a single bolus (group A) or as a serial loading method (group B) followed by measurement of loading vs. time and elution vs. time.
  
  
  RESULTS
  Phase I revealed the most effective loading mechanisms and easiest handling to be dry (group A) vs. normal saline prehydrated (group B) SAP with normal saline reconstituted doxorubicin (10 mg/mL) with loading efficiencies of 83.1% and 88.4%. Phase II results revealed unstable behavior of SAP with 100 mg of doxorubicin and similar loading/elution profiles of dry and prehydrated SAP, with superior handling characteristics of group B SAP at 50 and 75 mg.
  
  
  CONCLUSIONS
  SAP demonstrates the ability to load and bulk phase transfer doxorubicin at 50 and 75 mg with ease of handling and optimal efficiency through dry loading of SAP.
authors.affiliation: Department of Radiology, Vancouver General Hospital, University of British Columbia, 855 W 12th Ave., JP Pavillion G873, Vancouver, BC V5Z 1M9, Canada. dave.liu@vch.ca
authors.forename: David M
authors.initials: DM
authors.lastname: Liu
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kos
authors.forename: Andrzej
authors.initials: A
authors.lastname: Buczkowski
authors.forename: Stephen
authors.initials: S
authors.lastname: Kee
authors.forename: Peter L
authors.initials: PL
authors.lastname: Munk
authors.forename: Darren
authors.initials: D
authors.lastname: Klass
authors.forename: Ellen
authors.initials: E
authors.lastname: Wasan
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers; D008863:Microspheres; D011108:Polymers / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D011108:Polymers; D004317:Doxorubicin