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 bench-top 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 aqueous drainage device. To determine the ability to refill and also the patency of the cannula, at intervals of 4-6 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 by slit lamp examination, photography, and fluorescein angiography.

Results: Bench-top 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 mmHg. All implanted devices refilled at 4-6 weeks intervals for 4-6 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 pharmacological agents is needed to determine its ultimate potential for ophthalmic use.

Figure1

Concept of a refillable ocular mini drug pump. a. Conjunctiva b. Drug reservoir c. Sclera d. Cannula e. Cornea.

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. Suturing of suture tabs to sclera (upper left). Opening of AC through scleral tunnel ( upper right). Insertion of Cannula into anterior chamber ( lower left). Suturing of conjunctiva ( lower right).

Figure 9

Refilling of sham devices. Transconjunctival refilling of the device using a 30 gauge needle (left). Localizing of refill ring by transillumination (right).

Figure10

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

Figure 11

Examination of cornea by light microscopy. Implanted eye with some endothelial cells loss close to the tube site (left). Normal contra lateral eye (right, hematoxylin-eosin, x20).

Figure 12

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