Efficacy of paclitaxel released from bio-adhesive polymer microspheres on model superficial bladder cancer.
OBJECTIVE
We aimed to promote the efficacy of paclitaxel in intracavitary treatment of superficial transitional cell carcinoma of the bladder by designing bio-adhesive microspheres capable of achieving controlled release of the drug at the urothelium/urine interface.


METHODS
Poly(methylidene malonate 2.1.2) microspheres encapsulating paclitaxel were prepared by a single emulsion method. Bioactivity of the released paclitaxel was confirmed by assessing cytotoxicity on MBT-2, a bladder cancer cell line. Biodistribution of particles after bladder instillation was assessed by confocal microscopy and scanning electron microscopy. In vivo studies were performed in Balb/c mice after bladder cancer was induced by BBN (N-n-Butyl-N-butan-4-ol-nitrosamine) in drinking water. The efficacy of intravesical injections of conventional and microsphere paclitaxel was assessed by histology and survival rates.


RESULTS
Spherical 5 microm microspheres with 5% weight per weight paclitaxel loading ensured sustained release of bioactive paclitaxel. After bladder instillation the microspheres adhered to the mucosa and remained in the bladder lumen for at least 48 hours. In the BBN induced bladder cancer model compared with controls the 9-week survival rate was significantly improved by 2 injections of paclitaxel bio-adhesive microparticles. Microscopic evaluation confirmed the lower incidence of carcinoma in situ and high grade transitional cell carcinoma after injections of paclitaxel bio-adhesive microparticles compared with controls and with injections of similar doses of the conventional paclitaxel formulation.


CONCLUSIONS
Intravesical administration of poly(methylidene malonate 2.1.2) paclitaxel microspheres is a promising approach for intracavitary chemotherapy of superficial bladder cancer.
Le Visage
Catherine
C
Biomedical Engineering Department, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Rioux-Leclercq
Nathalie
N
Haller
Michael
M
Breton
Pascal
P
Malavaud
Bernard
B
Leong
Kam
K
D000269:Adhesives; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D017239:Paclitaxel / Q000008:administration & dosage*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000269:Adhesives; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel