ORIGINAL ARTICLE The uptake of paclitaxel and docetaxel into ex vivo porcine bladder tissue from polymeric micelle formulations Antonia Tsallas • John Jackson • Helen Burt Received: 19 May 2010 / Accepted: 26 October 2010 / Published online: 11 November 2010 Ó Springer-Verlag 2010 Abstract Superficial bladder cancer occurs in the uro- thelial 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 instilla- tion. 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-lm sections) and the amount of 3 H drug taken up into each section was deter- mined using liquid scintillation counting. Tissue concen- tration 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. Keywords Superficial bladder cancer  Intravesical drug delivery  Paclitaxel  Docetaxel Introduction The majority of bladder cancer patients present with superficial tumors and are effectively treated by transure- thral resection (TUR) methods [28]. However, more than 60% of cases will recur and approximately 15% of patients will develop deeper tumors that require radical surgery and systemic chemotherapy [5, 9]. Patients with superficial cancer are generally given immunotherapy, such as Bacillus Calmette-Guerin (BCG) or chemotherapy, such as mitomycin C or doxorubicin. These agents are introduced into the bladder for 2 h to eliminate any residual cancer cells [3, 22]. Although these chemotherapeutic methods may reduce short-term (2 year) recurrence rates, they have little effect on long-term outcome at 5 years [6, 26, 31, 32]. Systemic administration of anticancer agents is not indi- cated because the superficial tumors are located close to the surface urothelium, which is poorly vascularized. Clearly, the location of superficial bladder tumors sup- ports the strategy of intravesical drug administration since concentrated anticancer drug solutions may be readily instilled through a urethral catheter and then held directly next to the target tissues for a period of 2 h, until voiding. However, treatment failure is often ascribed to complete washout of drug upon voiding, poor uptake of drugs like mitomycin C and doxorubicin into the bladder wall and low sensitivity of tumors to these drugs [16]. Furthermore, significant inter-patient variability in the penetration of doxorubicin into bladder tissues has been reported that may be related to urine dilution and urothelium barrier properties [34]. A. Tsallas  J. Jackson  H. Burt (&) Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada e-mail: Burt@interchange.ubc.ca 123 Cancer Chemother Pharmacol (2011) 68:431–444 DOI 10.1007/s00280-010-1499-2