Nanoclay Crosslinked pH-Sensitive Hydrogel for Rhythmic Hormone Delivery

Abstract

Gonadotropin releasing hormone (GnRH) is secreted in rhythmic pulses every 1–2 hours. Disruption of this pulsatile release is associated with pathologies in reproductive function and sexual development. In order to approach an implantable, rhythmic delivery system for GnRH, a published prototype has been demonstrated that can generate rhythmic pulses of GnRH release in response to a constant glucose level. In this thesis, the prototype was altered with the intent to advance the development of a practical, implantable system. First, the commercial pH stat was replaced by a self-assembled one. The customized pH-stat was suitable for most titration conditions. Second, the durability of the membrane used in the system was improved. Third, the ratio of the membrane surface to the volume of delivery system was increased to speed up the systems oscillatory behavior. While these modifications improved the practicality of the delivery system, it resulted in the lose of pulsatile release behavior, for unknown reasons. A systematic approach is suggested, which can reveal the root cause analysis of the failure.