title: Paclitaxel gelatin nanoparticles for intravesical bladder cancer therapy.
abstract: OBJECTIVE
  We have noted that inadequate drug delivery to tumor cells is a major cause of failed intravesical therapy for nonmuscle invading bladder cancer, partly due to the dilution of drug concentration by urine production during treatment. To address this problem we developed gelatin nanoparticles of paclitaxel designed to yield constant drug concentrations. The hypothesis that a constant, therapeutic concentration in urine, bladder tissue and tumors can be attained was evaluated in dogs.
  
  
  METHODS
  We studied drug release from paclitaxel gelatin nanoparticles in culture medium in vitro. In vivo studies were performed in tumor-free dogs and in pet dogs with naturally occurring transitional cell carcinoma, in which the pharmacokinetics of paclitaxel gelatin nanoparticles were determined in plasma, urine and tumors.
  
  
  RESULTS
  Paclitaxel release from paclitaxel gelatin nanoparticles in vitro and in vivo was rate limited by the drug solubility in aqueous medium. This property yielded constant drug concentrations independent of changes in urine volume during the 2-hour treatment. Intravesical paclitaxel gelatin nanoparticles showed low systemic absorption, and favorable bladder tissue/tumor targeting and retention properties with pharmacologically active concentrations retained in tumors for at least 1 week.
  
  
  CONCLUSIONS
  Constant drug release from paclitaxel gelatin nanoparticles may overcome the problem of drug dilution by newly produced urine and the sustained drug levels in tumors may decrease treatment frequency.
authors.affiliation: Optimum Therapeutics, L.L.C., Columbus, Ohio, USA.
authors.forename: Ze
authors.initials: Z
authors.lastname: Lu
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Greg
authors.initials: G
authors.lastname: Lyness
authors.forename: Yan
authors.initials: Y
authors.lastname: Xin
authors.forename: M Guillaume
authors.initials: MG
authors.lastname: Wientjes
authors.forename: Valerie
authors.initials: V
authors.lastname: Bergdall
authors.forename: Guillermo
authors.initials: G
authors.lastname: Couto
authors.forename: Francisco
authors.initials: F
authors.lastname: Alvarez-Berger
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Kosarek
authors.forename: Jessie L-S
authors.initials: JL
authors.lastname: Au
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D004285:Dogs; D016503:Drug Delivery Systems; D005780:Gelatin; D006801:Humans; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005780:Gelatin; D017239:Paclitaxel