Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy

OBJECTIVE To develop paclitaxel incorporated into unimolecular micelles based on hydrophobically derivatized hyperbranched polyglycerols (dHPGs) for use as mucoadhesive intravesical agents against non‐muscle‐invasive bladder cancer. MATERIALS AND METHODS Two different types of dHPGs (HPG‐ C10‐polyet...

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Bibliographic Details
Published in:BJU international 2009-04, Vol.103 (7), p.978-986
Main Authors: Mugabe, Clement, Hadaschik, Boris A., Kainthan, Rajesh K., Brooks, Donald E., So, Alan I., Gleave, Martin E., Burt, Helen M.
Format: Article
Language:English
Subjects:
Administration, Intravesical
Animals
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - pharmacology
Biological and medical sciences
bladder cancer
Cell Line, Tumor
Drug Delivery Systems - methods
Humans
hyperbranched polyglycerols
intravesical therapy
Medical sciences
Mice
Mice, Nude
Nanoparticles
Nephrology. Urinary tract diseases
orthotopic mouse model
paclitaxel
Paclitaxel - administration & dosage
Paclitaxel - pharmacology
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - chemistry
Polyethyleneimine - administration & dosage
Polyethyleneimine - chemistry
Tumors of the urinary system
unimolecular micelles
Urinary Bladder Neoplasms - drug therapy
Urinary system involvement in other diseases. Miscellaneous
Urinary tract. Prostate gland
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Summary:OBJECTIVE To develop paclitaxel incorporated into unimolecular micelles based on hydrophobically derivatized hyperbranched polyglycerols (dHPGs) for use as mucoadhesive intravesical agents against non‐muscle‐invasive bladder cancer. MATERIALS AND METHODS Two different types of dHPGs (HPG‐ C10‐polyethylene glycol (PEG) and polyethyleneimine (PEI)‐C18‐HPG) were synthesized and paclitaxel was loaded into these using a solvent evaporation method. After physicochemical characterization of the resulting nanoparticles, four human bladder cancer cell lines were incubated with various concentrations of paclitaxel incorporated in dHPGs and the results were compared with those of paclitaxel formulated in Cremophor‐EL (Taxol®, Bristol‐Myers‐Squibb). In vivo, nude mice with orthotopic KU7‐luc tumours were intravesically instilled with phosphate buffered saline, Taxol, or paclitaxel/HPG‐C10‐PEG. RESULTS dHPGs are mucoadhesive nanoparticles with hydrodynamic radii of
ISSN:1464-4096
1464-410X
DOI:10.1111/j.1464-410X.2008.08132.x