title: Intratracheal Administration of Hyaluronan-Cisplatin Conjugate Nanoparticles Significantly Attenuates Lung Cancer Growth in Mice.
abstract: To determine aerosol administration capability and therapeutic efficacy of the new formulation of hyaluronan cisplatin conjugates, HylaPlat™ (HA-Pt), for lung cancer treatment.
  
  
  
  In vitro formulation stability test, 2D and 3D spheroid cell culture and in vivo efficacy studies using mouse orthotopic allograft models were conducted.
  
  
  
  The HA-Pt effectively attenuated cell growth in 2D and 3D cultures with IC50 of 2.62 and 5.36 μM, respectively, which were comparable to those with unconjugated control cisplatin-dependent growth inhibition (IC50 1.64 and 4.63 μM, respectively). A single dose of either 7.5 or 15 mg/kg HA-Pt (cisplatin equivalent) by intratracheal aerosol spray 7 days after Lewis lung carcinoma (LLC) cell inoculation markedly inhibited growth of LLC allografts in mouse lungs and resulted in a 90 or 94% reduction of tumor nodule numbers, respectively, as compared to those from the PBS control. Cancer stem cells and cisplatin resistant cells marker, CD44 expression decreased in the tumor nodules of the HA-Pt but not in those of cisplatin treated groups.
  
  
  
  The current study suggests that an intratracheal aerosol administration of the HA-Pt nanoparticles offers an effective strategy for lung cancer treatment and this treatment may induce only limited cisplatin resistance.
authors.affiliation: Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, 210 Coles Hall, Manhattan, Kansas, 66506, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishiguro
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, Kansas, 66047, USA.|HylaPharm LLC, Lawrence, Kansas, 66047, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, 210 Coles Hall, Manhattan, Kansas, 66506, USA.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Uppalapati
authors.affiliation: Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, 210 Coles Hall, Manhattan, Kansas, 66506, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Turner
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, Kansas, 66047, USA.
authors.forename: Ti
authors.initials: T
authors.lastname: Zhang
authors.affiliation: HylaPharm LLC, Lawrence, Kansas, 66047, USA.
authors.forename: Wai Chee
authors.initials: WC
authors.lastname: Forrest
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, Kansas, 66047, USA.|HylaPharm LLC, Lawrence, Kansas, 66047, USA.
authors.forename: M Laird
authors.initials: ML
authors.lastname: Forrest
authors.affiliation: Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, 210 Coles Hall, Manhattan, Kansas, 66506, USA. mtamura@vet.k-state.edu.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tamura
mesh_terms: D000072283:A549 Cells; D000280:Administration, Inhalation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000008:administration & dosage* / Q000378:metabolism; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006820:Hyaluronic Acid; D002945:Cisplatin
keywords: CD44; apoptosis; hyaluronan-cisplatin conjugates nanoparticle; lung cancer; pulmonary chemotherapy