Abstract
To prevent implant failure due to fibrosis is a major objective in glaucoma research. The present study investigated the antifibrotic effects of paclitaxel (PTX), caffeic acid phenethyl ester (CAPE), and pirfenidone (PFD) coated microstent test specimens in a rat model. Test specimens based on a biodegradable blend of poly(4-hydroxybutyrate) biopolymer and atactic poly(3-hydroxybutyrate) (at.P(3HB)) were manufactured, equipped with local drug delivery (LDD) coatings, and implanted in the subcutaneous white fat depot. Postoperatively, test specimens were explanted and analyzed for residual drug content. Fat depots including the test specimens were histologically analyzed. In vitro drug release studies revealed an initial burst for LDD devices. In vivo, slow drug release of PTX was found, whereas it already completed 1 week postoperatively for CAPE and PFD LDD devices. Histological examinations revealed a massive cell infiltration in the periphery of the test specimens. Compact fibrotic capsules around the LDD devices were detectable at 4–36 weeks and least pronounced around PFD-coated specimens. Capsules stained positive for extracellular matrix (ECM) components. The presented model offers possibilities to investigate release kinetics and the antifibrotic potential of drugs in vivo as well as the identification of more effective agents for a novel generation of drug-eluting glaucoma microstents.
Highlights
Glaucoma is a leading cause of irreversible blindness worldwide and is mostly characterized by an increased intraocular pressure (IOP), which results from disturbances in the outflow of aqueous humor from the eye
Test specimens were composed of tubing and an local drug delivery (LDD) coating, both manufactured based on biodegradable polymeric materials
Slow in vitro drug release within a time frame of 5–6 weeks was found for PTX and caffeic acid phenethyl ester (CAPE) LDD devices.On the contrary, PFD LDD devices showed fast in vitro drug release within 10 h (Figure 2B)
Summary
Glaucoma is a leading cause of irreversible blindness worldwide and is mostly characterized by an increased intraocular pressure (IOP), which results from disturbances in the outflow of aqueous humor from the eye. Increased pressure conditions lead to damage of the retinal ganglion cells and degeneration of the optic nerve fibers, resulting in a loss of vision and blindness, if untreated [1]. Reduction in IOP is the only available treatment to prevent nervous degeneration [2,3]. Medicinal therapy represents the first-line treatment for IOP lowering [4,5]. In case of insufficient IOP reduction by means of medicinal therapy, surgical interventions have been used to drain aqueous humor from the anterior chamber of the eye into an extraocular compartment. Cyclophotocoagulation [9,10] provides an alternative therapy to lower IOP by decreasing the aqueous humor production
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