Development of a biodegradable antifibrotic local drug delivery system for glaucoma microstents

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.

Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis

“…The analysis of the drug release from the sintered PLA@PF implants was performed in vitro in physiological conditions (PBS, 37 °C). This experiment demonstrated that the complete release of PF from PLA@PF implants was prolonged to 80 h, following the initial more rapid release of approximately 50% of the drug during first 20 h. This release time was much longer than the period reported for the different types of PF-loaded ocular lenses (up to 12 h) [ 70 , 71 ].…”

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

“…A total of 16.12 µg PFD was released within a time frame of 10 h in vitro. Disregardless of the relatively fast drug release the PFD coating effectively reduces capsule thickness and the growth of the capsule throughout the 6 months observation period [5].…”

“…A valve mechanism is used for controlled drainage of aqueous humour, a drug eluting-coating focusses on the prevention of fibrosis and an injector device is used for minimally invasive ab interno implantation into suprachoroidal or alternatively subconjunctival space ( Fig. 1) [5][6][7]. PFD loading of the drug eluting coating was chosen according to Jung et al who implanted conventional Ahmed FP8 GDD (New World Medical Inc., USA) into New Zealand White rabbits adjunctive with an intraoperative injection of 200 µg PFD in a 200 µl solution incorporated with 1 mg ml -1 PFD [4].…”

“…Pirfenidone (PFD) as a treatment option of idiopathic pulmonary fibrosis has been identified as a promising drug for the inhibition of fibrosis in animal models, such as New Zealand White rabbits or rats [4,5]. Therefore, the current work focusses on the development of an antifibrotic drugeluting coating for a minimally invasive implantable glaucoma microstent.…”

Medical device innovations for cardiovascular, ophthalmologic and otolaryngologic applications

“…Apart from the cardiovascular system, stents are being researched in ophthalmologic (glaucoma drainage) [4,5], otorhinolaryngologic (Eustachian tube, treatment of chronic otitis media) [6], as well as gynecologic (Fallopian tube), see Figure 2, and gastroenterologic (pancreas) application. The latter being applied in the context of endoscopic pancreatic necrosectomy [7], see Figure 3.…”