title: Effects of intratumoral administration of a hyaluronan-cisplatin nanoconjugate to five dogs with soft tissue sarcomas.
abstract: OBJECTIVE
  To determine the effects of intratumoral injection of a hyaluronan-cisplatin nanoconjugate on local and systemic platinum concentrations and systemic toxicosis.
  
  
  METHODS
  5 dogs with spontaneous soft tissue sarcomas (STSs).
  
  
  METHODS
  For each dog, approximately 1.5 mL of hyaluronan nanocarrier conjugated with 20 mg of cisplatin was injected into an external STS. Blood samples were collected immediately before (0 hours) and at 0.5, 1, 2, 3, 4, 24, and 96 hours after hyaluronan-cisplatin injection for pharmacokinetic analyses. Urine samples were obtained at 0 and at 96 hours after hyaluronan-cisplatin injection for urinalysis. Each treated STS and its sentinel lymph nodes were surgically removed 96 hours after the hyaluronan-cisplatin injection. Inductively coupled plasma mass spectrometry was used to measure platinum concentrations in blood samples, tumors, and lymph nodes.
  
  
  RESULTS
  No tissue reactions were detected 96 hours after hyaluronan-cisplatin injection. Mean ± SD area under the curve, peak concentration, and terminal half-life for unbound (plasma) and total (serum) platinum were 774.6 ± 221.1 ng•h/mL and 3,562.1 ± 2,031.1 ng•h/mL, 56.5 ± 20.9 ng/mL and 81.6 ± 40.4 ng/mL, and 33.6 ± 16.1 hours and 51.2 ± 29.1 hours, respectively. Platinum concentrations ranged from 3,325 to 8,229 ng/g in STSs and 130 to 6,066 ng/g in STS-associated lymph nodes.
  
  
  CONCLUSIONS
  Intratumoral injection of the hyaluronan-cisplatin nanoconjugate was well tolerated in treated dogs. Following intratumoral hyaluronan-cisplatin injection, platinum concentration was 1,000-fold and 100-fold greater within treated tumors and tumor-draining lymphatics, respectively, compared with that in plasma.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Rachel O
authors.initials: RO
authors.lastname: Venable
authors.forename: Deanna R
authors.initials: DR
authors.lastname: Worley
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Gustafson
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hansen
authors.forename: E J
authors.initials: EJ
authors.lastname: Ehrhart
authors.forename: Shuang
authors.initials: S
authors.lastname: Cai
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cohen
authors.forename: M Laird
authors.initials: ML
authors.lastname: Forrest
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D005260:Female; D006207:Half-Life; D006820:Hyaluronic Acid / Q000009:adverse effects*; D007271:Injections, Intradermal / Q000662:veterinary; D061305:Lymphoscintigraphy / Q000662:veterinary; D008297:Male; D013058:Mass Spectrometry / Q000662:veterinary; D058726:Nanoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D010984:Platinum / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D058726:Nanoconjugates; D010984:Platinum; D006820:Hyaluronic Acid; D002945:Cisplatin