Novel Hydrogels for Rhythmic Pulsatile Drug Delivery

Abstract

Summary:We are investigating an autonomous glucose-driven hydrogel/enzymebased device prototype for rhythmic, pulsed delivery of gonadotropin releasing hormone (GnRH). The device employs a pH-sensitive hydrogel membrane in conjunction with the enzyme glucose oxidase. This system delivers GnRH in rhythmic pulses when exposed to a constant level of glucose. These pulses result from autonomous pH oscillations inside the device that are created by an unstable nonlinear feedback between hydrogel permeability to glucose and production of acid by glucose oxidase. Previous versions of this prototype utilized p(N-isopropylacrylamide-co-methylacrylic acid) p(NIPA-co-MAA) hydrogels, with 10 mol% MAA incorporated. With this membrane, which undergoes a volume transition (VT) near pH 5, pH oscillations centered around pH 5 are observed. This range is too low to sustain oscillations in physiologically buffered media. To shift the operating pH of oscillations closer to physiologic pH, we have sought ways to increase the pH of the volume transition. In this study we show that increasing the side chain length of the a-alkylacrylic acid (RAA) comonomer enhances the overall hydrophobicity of the copolymer, and shifts the VT pH closer to physiological pH values. We also demonstrate the ability of such membranes to affect an alkaline shift in the range of oscillations in the prototype oscillator device.

Self-regulated intelligent systems: where adaptive entities meet chemical oscillators

“…Three kinds of representative chemical oscillators, BZ reaction, 22,23,68 pH oscillator [97][98][99][100][101][102][103][104][105][106][107] and biological oscillator, [108][109][110][111] are generally utilized to construct functional and autonomous actuators. Generally, the BZ reaction is used because of its versatility and self-sustaining characteristic that ensures the oscillating reaction proceeds in a completely closed system.…”

Chemoelastodynamics of Responsive Gels

“…The most typical are copolymers of N-isopropylacrylamide and acrylic acid (poly(NiPAAm-co-AAc)), which exhibit quasi-first order volume collapse when the pH of the solvent drops below 5. This critical pH value can be increased (decreased) by increasing the hydrophobicity (hydrophilicity) of the network [60][61][62]. Gels that shrink in an alkaline medium and swell in neutral or acidic medium are obtained for networks with a basic moiety.…”

Controlled and time‐scheduled drug delivery: Polyanhydride‐based nanoparticles as ocular medication carriers

“…Clearly, responding to such complex demands requires similarly complex well‐engineered modalities. For example, is the most uncommon case of a pulsed delivery of gonadotropin releasing hormone to respond to the demands of the metabolic pathway addressed 2 . Another example is the complex system intended for releasing a drug to prevent blood vessel restenosis at the defined location of a vascular stent.…”

“…For example, is the most uncommon case of a pulsed delivery of gonadotropin releasing hormone to respond to the demands of the metabolic pathway addressed. 2 Another example is the complex system intended for releasing a drug to prevent blood vessel restenosis at the defined location of a vascular stent. This was achieved by using the enzyme nitric oxide synthase immobilized onto the stent, which then locally converts the non-active prodrug L-Arginine into the active drug nitric oxide.…”