On-demand controlled release of docetaxel from a battery-less MEMS drug delivery device

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This paper discusses a delivery mechanism for treatment of late stage proliferative retinopathy in diabetic patients. They propose a delivery mechanism for targening docetaxel (a taxane). Taxanes are antiproliferative drugs that produce an antiangiogenic effect at low nanomolar concentrations. However, taxanes are quickly removed from the blood so you either need large doses (which increase toxicity to other tissues), or a drug delivery mechanism as proposed.

Desired characteristics of such a delivery device are: (1) controlled and on-demand dosing, (2) biocompatability, (3) minimum drug degradation within the device over the period of implantation, and (4) localized drug delivery to minimize systemic toxicities. You can’t use electro-mechanical because you need a battery. Alternative is using a magentic external stimulant source to get rid of the battery, but for chronic illnesses this is not ideal. However, non magnetic sources can provide unreliable dosages, so the paper focuses on a magnetic powered delivery mechanism.

The proposed device

Delivers docetaxel (DTX). Consists of a drug-loaded micro-resevoir sealed by an electromagnetic PDMS membrane with a laser drilled aperature. With a magnetic field, the membrane deforms and discharges the drug solution out of the resevoir. Timing/dosage can be controlled by the applied magnetic field strength and the on-demand time of actuation. The chip was made with Su-8 and photolithography techniques. And the magnetic membrane was made by incorporating coated iron oxide particles, EMG 1200, in a PDMS matrix.

For exact materials/methods read the paper.

Essentially the reason you can do multiple doses is because the drug has low solubility. Thus, when you mix in the physiological solution during an actuation only some of it will mix into the solution. To determine the necessary mixing time, the following equation was used:

$$\frac{\delta c}{\delta t} + u \nabla c = \nabla (D \nabla c)$$ Here, $c$ is concentration of the solute ($\text{mol m}^{-3}$), $D$ denotes the diffusion coefficient ($\text{m}^2 \text{s}^{-1}$), and $u$ is the velocity vectore.

The discharge time can be estimated with the equation:

$$t_d = \frac{V_d}{A_a v}$$ Where $A_a$ is teh area of the aperature, $v$ denotes the velocity of the dischargin liquid, and $V_d$ is obtained using $V_d = \frac{d}{3}A_m$ where $d$ is the estimated deflection of the membrane, and $A_m$ is the area of the circular membrane.

Overall, while the method of release here seems to be novel, there is much work to be done and significant testing/analysis before in vivo implantation of such devices can be done. One particular setback seems to be the leakage of the drug between actuations, which really isn’t acceptable for something claiming to be meant for precision delivery.

Written on October 13, 2014