Mini drug pump for ophthalmic use

Abstract

Purpose: To evaluate the feasibility of developing a novel mini drug pump for ophthalmic use.

Methods: Using principles of microelectromechanical systems engineering, a mini drug pump was fabricated. The pumping mechanism is based on electrolysis, and the pump includes a drug refill port as well as a check valve to control drug delivery. Drug pumps were tested first on the benchtop and then after implantation in rabbits. For the latter, we implanted 4 elliptical (9.9 x 7.7 x 1.8 mm) non-electrically active pumps into 4 rabbits. The procedure is similar to implantation of a glaucoma seton. To determine the ability to refill and also the patency of the cannula, at intervals of 4 to 6 weeks after implantation, we accessed the drug reservoir with a transconjunctival needle and delivered approximately as low as 1 microL of trypan blue solution (0.06%) into the anterior chamber. Animals were followed up by slit-lamp examination, photography, and fluorescein angiography.

Results: Benchtop testing showed 2.0 microL/min delivery when using 0.4 mW of power for electrolysis. One-way valves showed reliable opening pressures of 470 mm Hg. All implanted devices refilled at 4- to 6-week intervals for 4 to 6 months. No infection was seen. No devices extruded. No filtering bleb formed over the implant.

Conclusions: A prototype ocular mini drug pump was built, implanted, and refilled. Such a platform needs more testing to determine the long-term biocompatibility of an electrically controlled implanted pump. Testing with various pharmacologic agents is needed to determine its ultimate potential for ophthalmic use.

FIGURE 1

Concept of a refillable ocular mini drug pump showing conjunctiva (a), drug reservoir (b), sclera (c), cannula (d), and cornea (e).

FIGURE 2

Gas bubble evolution resulting from electrolysis in drug reservoir of packaged electrically controlled device.

FIGURE 3

Non-electrically controlled mini drug pump.

FIGURE 4

Schematic model of first generation manually controlled mini drug pump. 3-D rendered image of the device (left). An exploded view showing the individual layers (right).

FIGURE 5

Packaged electrically controlled mini drug pump.

FIGURE 6

Trypan blue solution dispensation into anterior chamber in non-electrically controlled mini drug pump after manual pressure with blunt forceps.

FIGURE 7

Sham mini drug pump.

FIGURE 8

Surgical implantation of sham devices in rabbits. Top left, Suturing of suture tabs to sclera. Top right, Opening of anterior chamber through scleral tunnel. Bottom left, Insertion of cannula into anterior chamber. Bottom right, Suturing of conjunctiva.

FIGURE 9

Refilling of sham devices. Left, Transconjunctival refilling of the device using a 30-gauge needle. Right, Localizing of refill ring by transillumination.

FIGURE 10

Color photography (left) and fluorescein angiography (FA) of the anterior (middle) and posterior (right) segments in a representative rabbit at 6 months.

FIGURE 11

Pump testing in electrically controlled mini drug pump. Left, Current-controlled flow rate after evaporation compensation. Right, Low flow rate operation of the pump. (Reprinted with permission from Elsevier.12)

FIGURE 12

Bolus delivery of 250-nL doses using current pulses in electrically controlled mini drug pump. (Reprinted with permission from Elsevier.12)

FIGURE 13

Flow rate changes in different intraocular pressures in electrically controlled mini drug pump. (Reprinted with permission from Elsevier.12)

FIGURE 14

Examination of cornea by light microscopy. Left, Implanted eye with some endothelial cell loss close to the tube site. Right, Normal contralateral eye (hematoxylin-eosin, ×20).

FIGURE 15

Examination of corneal endothelium by scanning electron microscopy (SEM) after implantation of sham devices for 6 months. Left, Implanted eye. Middle, Normal control eye. Right, Implanted eye after discontinuation of trypan blue solution refilling at 4 months after surgery (white bar = 50 μm).