Drug delivery device for bladder disorders

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 100-104).Several pathologies associated with the bladder have wide impacts on society. Overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS) are chronic urological conditions characterized by pain, urinary frequency, and urgency with or without urinary incontinence. The estimated prevalence of OAB and IC/PBS is more than 34 million people in the U.S. alone. The American Cancer Society estimated a total of 68,810 new bladder cancer cases and 14,100 deaths from bladder cancer in the U.S. in 2008. Treatment options include oral medications, transdermal patches and intravesical instillations of therapeutic solutions. Direct intravesical instillation is considered an effective option, especially for those who remain refractory to oral and transdermal formulations due to intolerable side effects and skin irritations, respectively. Intravesical treatment, however, requires repeated instillations due to rapid drug voiding by urination, and the frequent urinary catheterizations involve risk of urinary infection and patient discomfort. An alternative, site-specific local delivery approach was created using a reservoir-based drug delivery device. This novel passive device was designed to release drug in a predetermined manner once inside the bladder. The device also possesses a retention feature to prevent accidental voiding. The device can be implanted into and retrieved from the bladder by a non-surgical cystoscopic procedure.(cont.) In vivo tests using lidocaine, a local anesthetic used for IC/PBS treatment, showed that a sustained and local treatment to the bladder can be achieved with the device. The lidocaine bladder tissue concentration was found to be a thousand-fold higher than the lidocaine plasma concentration at three and six days in a rabbit model. The device approach has the potential to achieve localized therapy to the bladder while minimizing side effects. Future studies may use the device for other therapeutic agents in the treatment of OAB, IC/PBS, and bladder cancer.by Heejin Lee.Ph.D