The uptake of paclitaxel and docetaxel into ex vivo porcine bladder tissue from polymeric micelle formulations.
Superficial bladder cancer occurs in the urothelial layer of the bladder and is usually treated by transurethral resection and chemotherapy. Although the bladder is well suited for intravesical chemotherapy, effective drug delivery is restricted by urine dilution and poor drug uptake by bladder tissues during a 2 h instillation. In this study, freshly excised pig bladder sections were mounted on Franz diffusion cells and treated with anticancer drugs paclitaxel (PTX) and docetaxel (DTX) formulated in diblock copolymer (methoxy poly(ethylene glycol)-block-poly (D,L-lactic acid) (MePEG-PDLLA) and methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-PCL) nanoparticles for 2 h. The bladder sections were then frozen, cryosectioned (60-μm sections) and the amount of (3)H drug taken up into each section was determined using liquid scintillation counting. Tissue concentration versus tissue depth profiles were obtained for all drug formulations and drug exposure obtained from area-under-the-curve (AUC) calculations. PTX or DTX loaded in MePEG-PDLLA micelles produced significantly higher urothelial tissue levels and greater bladder wall exposures compared to their commercial formulations, Cremophor EL/ethanol (PTX) or Tween 80 (DTX). The results of this study support the use of diblock copolymer micellar PTX or DTX formulations as they allow for improved drug penetration of bladder tissues compared to commercial formulations for taxane delivery to superficial bladder tumors.
University of British Columbia, Vancouver, V6T 1Z3, Canada.
Antonia
A
Tsallas
John
J
Jackson
Helen
H
Burt
D000283:Administration, Intravesical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D001692:Biological Transport; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D004339:Drug Compounding; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D066298:In Vitro Techniques; D008297:Male; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D013552:Swine; D043823:Taxoids / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000737:chemistry / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D014677:Pharmaceutical Vehicles; D011091:Polyesters; D011136:Polysorbates; D043823:Taxoids; C561465:methoxy poly(ethylene glycol)-block-poly(lactic acid); C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D000077143:Docetaxel; D011092:Polyethylene Glycols; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol