HYTAD1-p20: A new paclitaxel-hyaluronic acid hydrosoluble bioconjugate for treatment of superficial bladder cancer
| Autor: | Gilda De Luca, Fabio Bettella, Pierfrancesco Bassi, Claudio Pagano, Davide Renier, Giovanni Esposito, Antonio Rosato, Paola Zanovello, Alessandra Banzato |
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| Rok vydání: | 2006 |
| Předmět: |
Pathology
medicine.medical_specialty Maximum Tolerated Dose Paclitaxel Urology Urinary Bladder Mice SCID Mice chemistry.chemical_compound Drug Delivery Systems Pharmacokinetics In vivo Hyaluronic acid otorhinolaryngologic diseases medicine Animals Humans Tissue Distribution Hyaluronic Acid Chromatography High Pressure Liquid Mice Inbred BALB C Bladder cancer biology business.industry CD44 medicine.disease Antineoplastic Agents Phytogenic In vitro Administration Intravesical Hyaluronan Receptors Urinary Bladder Neoplasms Oncology chemistry Cancer cell Cancer research biology.protein Female business |
| Zdroj: | Urologic Oncology: Seminars and Original Investigations. 24:207-215 |
| ISSN: | 1078-1439 |
| Popis: | Objective To report the development of a new water-soluble paclitaxel-hyaluronic acid bioconjugate, HYTAD1-p20, for intravesical treatment of superficial bladder cancer. Materials and 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. |
| Databáze: | OpenAIRE |
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