title: HYTAD1-p20: a new paclitaxel-hyaluronic acid hydrosoluble bioconjugate for treatment of superficial bladder cancer.
abstract: OBJECTIVE
  To report the development of a new water-soluble paclitaxel-hyaluronic acid bioconjugate, HYTAD1-p20, for intravesical treatment of superficial bladder cancer.
  
  
  METHODS
  HYTAD1-p20 was synthesized by carboxyl esterification of hyaluronic acid with paclitaxel, and its physicochemical and biologic properties were characterized.
  
  
  RESULTS
  Paclitaxel loading was optimized at 20% w/w; this procedure increased by 500-fold the paclitaxel concentration in the resulting water-soluble biomaterial. In vitro, HYTAD1-p20 exerted a much higher dose-dependent inhibitory effect against RT-4 and RT-112/84 bladder carcinoma cell growth than that of free drug, and directly interacted with CD44 expressed by bladder tumor cells. In vivo, results of pharmacokinetic studies performed in mice after bladder catheterization and intravesical instillation of HYTAD1-p20 disclosed that drug leakage was negligible during a 2-hour analysis. Histologic examination of drug-instilled bladders revealed that HYTAD1-p20 was extremely well tolerated, while paclitaxel alone produced mucosal disruption and submucosal infiltration of inflammatory cells. Treatment of severe combined immunodeficient mice bearing subcutaneous RT-112/84 tumors with maximum tolerated doses of bioconjugate or paclitaxel showed that HYTAD1-p20 exerted a therapeutic activity comparable to that of free drug.
  
  
  CONCLUSIONS
  These data suggest that HYTAD1-p20 significantly improved results obtained with conventional paclitaxel in terms of hydrosolubility, in vitro activity against human bladder cancer cells, and in vivo biocompatibility. This bioconjugate is a potentially useful treatment for superficial urothelial malignancy.
authors: Department of Oncology and Surgical Sciences, Oncology Section, University of Padua, Padua, Italy. antonio.rosato@unipd.it
authors: Antonio
authors: A
authors: Rosato
authors: Alessandra
authors: A
authors: Banzato
authors: Gilda
authors: G
authors: De Luca
authors: Davide
authors: D
authors: Renier
authors: Fabio
authors: F
authors: Bettella
authors: Claudio
authors: C
authors: Pagano
authors: Giovanni
authors: G
authors: Esposito
authors: Paola
authors: P
authors: Zanovello
authors: PierFrancesco
authors: P
authors: Bassi