Development of an antifibrotic drug-eluting coating for a minimally invasive implantable glaucoma microstent

Abstract

Primary open angle glaucoma represents an eye disease that usually is associated with an increased intraocular pressure (IOP). Implants for micro-invasive glaucoma surgery (MIGS) are gaining importance as a promising option for IOP lowering. Currently available devices are implanted into the eye ab interno based on a clear corneal incision and drain aqueous humour into the schlemm’s canal, suprachoroidal or subconjunctival space. Fibrosis is known as a major limitation for long term success and often leads to the necessity of an additional medication or a surgical re-intervention. The current work focusses on the development of an antifibrotic drug-eluting coating for a minimally invasive implantable glaucoma microstent. Tubular microstent base bodies manufactured from a polycarbonate based silicone elastomer were spray-coated with a chloroform based mixture of the same polymer and the antifibrotic drug pirfenidone (PFD, P2116, Merck KGaA, Germany) in a polymer/drug ratio of 85/15% (w/w). Coating mass of 89 μg according to a drug loading of 1.96 μg mm-2 was aspired. Coating mass was measured using an ultramicrobalance (XP6U, Mettler-Toledo International, Inc., Switzerland). Glaucoma microstent prototypes with a drugeluting coating mass of (84 ± 19) μg (n = 12) were manufactured. Characterization by means of scanning electron microscopy (Quattro S, Thermo Fisher Scientific, FEI Deutschland GmbH, Germany) yielded a reproducible smooth surface of the coating. High performance liquid chromatography (KNAUER Wissenschaftliche Geräte GmbH, Germany) was used for analysis of drug release behaviour in 0.9% NaCl solution at 37°C. The in vitro PFDrelease is characterized by an initial burst phase of approximately 6 h followed by a more retarded release phase. The entire drug was released within 36 h (n = 3). Sterilization processing has a minor impact on drug release kinetics. Appropriate drug stability after sterilization could be proven. Future studies will focus on the antifibrotic properties of drug-eluting glaucoma microstents in animal studies.

Development of a limbal fixation mechanism for a minimally invasive implantable glaucoma microstent

“…The presented fixation protoypes were used for a proof of concept but could not jet be used in combination with our applicator device [2,3]. Future studies will focus on adaption of the mechanical properties of the retention force in vitro model [5].…”

“…2.). The concept of microstent implantation into subconjunctival or suprachoroidal space using different applicator devices was described previously [2,3]. The MIGS-procedure is based on a 22G x 1½" cannula (inner diameter IDc = 0.47 mm, outer diameter ODc = 0.70 mm, length lc = 40 mm) [2].…”

“…The MIGS-procedure is based on a 22G x 1½" cannula (inner diameter IDc = 0.47 mm, outer diameter ODc = 0.70 mm, length lc = 40 mm) [2]. The microstent itself (IDm = 0.20 mm, ODm = 0.36 mm, lc = 10 mm) fits loosely into this cannula [3]. Considering the inner cannula diameter, overall microstent diameter in the crimped state must not exceed 0.47 mm.…”

“…We previously presented our innovative concept of a drug-eluting glaucoma microstent for MIGS ( Fig. 1) [2,3]. Stable intraocular fixation represents a crucial aspect of ab interno implantable devices.…”

Transfer activities for cardiovascular, ophthalmologic and otolaryngologic medical device innovations

“…A clinical translation of ophthalmic implants for glaucoma treatment is aspired [3], as well as of otolaryngologic stents for the treatment of Eustachian tube dysfunction [4].…”