Design and in vitro development of resorbable urologic drug delivery device

Abstract

Implantable, controlled release drug delivery devices offer several advantages over systemic oral administration routes and immediate drug release treatments including direct therapy to target organ, more continuous maintenance of plasma and tissue drug levels and the potential for reduced side effects or toxicity. Urology has emerged as a unique field in which minimally invasive implantation techniques are available and such devices could provide improved beneficial therapies over conventional treatments. Urological indications for which localized drug therapy is already being advocated and investigated are highly suitable for treatment with implantable controlled release devices. This thesis describes the in vitro performance evaluation of an implantable, bio-resorbable device that can provide localized drug therapy of ciprofloxacin (CIP) to the seminal vesicle and nearby prostate gland for treatment of chronic prostatitis (CP). The device functions as an elementary osmotic pump (EOP) to release CIP for a period of 2-3 weeks after implantation in the seminal vesicle (SV) through transrectal needle injection or cystoscopic methods. The device is composed of an elastomeric, resorbable polymer cast in a tubular geometry with solid drug powder packed into its core and a micromachined release orifice drilled through its wall. Drug release experiments were performed to determine the effective release rate from a single orifice and the range of orifice size in which osmotic-controlled zero-order release was the dominant mechanism of drug delivery from the device. Device stability and function in an alkaline environment of similar pH to that of the SVs and infected prostate gland was also assessed in vitro. The device was found to function well in both de-ionized water and NaOH pH-8 solution with a sustained zero-order release rate of 2.47 ± 0.29 jtg/hr when fabricated with an orifice of diameter 100-150pm.