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Elevated intraocular pressure is the main risk factor for glaucoma and its adjustment to physiological levels can prevent progression of the disease. If conventional drop-based glaucoma therapy fails, surgical interventions such as trabeculectomy or the application of implants, which drain aqueous humour from the eye and thus reduce intraocular pressure, are used as final therapeutic procedures. These interventions are becoming increasingly minimally invasive and the drainage implants are getting steadily smaller, which is why these interventions are now called microinvasive glaucoma surgery (MIGS). Both, surgery and drainage implant-based glaucoma therapy are limited by wound healing processes and fibrosis that occlude the newly created drainage pathways for the aqueous humour. To suppress unwanted postoperative fibrosis coupled with an increased extracellular matrix production, cytostatics like mitomycin c or 5- fluorouracil are currently used, which are associated with side effects. Therefore, more specific antifibrotic agents are key for a durable functionality of the interventions in glaucoma therapy. In this study a specific active substance (pirfenidone, PFD) was added in a polymer matrix for controlled release. Previous studies have shown that the release of pirfenidone from a thermoplastic silicone polycarbonate elastomer, which could be used as a material for a glaucoma drainage implant, has been relatively fast. To decelerate the release the influence of the alternate polymers Poly-L-Lactide (PLLA) and Poly-D,LLactide (PDLLA) as alternative drug carriers was investigated. Furthermore, a reduction of the pirfenidone content was used to delay the release.

Extrusion is a common manufacturing process for semi-finished polymer products in various biomedical applications. Extrusion enables processing of a wide range of biomaterials, as well as different cross-sectional geometries. Furthermore, feasibility of drug elution, as it is used for a variety of medical devices, for example microstents for minimally invasive glaucoma therapy, was assessed. The current study deals with manufacturing of polymeric microtubes by extrusion processing. Semi-finished products were made of biodegradable poly-L-lactide (PLLA) and a non-biodegradable polycarbonate-based silicone elastomer (SIL) and covered with a polymer/drug combination, with resveratrol as active ingredient. Three different concentrations of polymer/resveratrol were applied by means of spray-coating. The release behavior of active ingredient was analyzed in vitro at 37°C and showed a correlation between the amount of drug and release time. With higher drug content, a faster release was observed. In addition, the release from SIL was faster compared with PLLA.

Local drug delivery has become indispensable in biomedical engineering with stents being ideal carrier platforms. While local drug release is superior to systemic administration in many fields, the incorporation of drugs into polymers may influence the physico-chemical properties of said matrix. This is of particular relevance as minimally invasive implantation is frequently accompanied by mechanical stresses on the implant and coating. Thus, drug incorporation into polymers may result in a susceptibility to potentially life-threatening implant failure. We investigated spray-coated poly-l-lactide (PLLA)/drug blends using thermal measurements (DSC) and tensile tests to determine the influence of selected drugs, namely sirolimus, paclitaxel, dexamethasone, and cyclosporine A, on the physico-chemical properties of the polymer. For all drugs and PLLA/drug ratios, an increase in tensile strength was observed. As for sirolimus and dexamethasone, PLLA/drug mixed phase systems were identified by shifted drug melting peaks at 200 °C and 240 °C, respectively, whereas paclitaxel and dexamethasone led to cold crystallization. Cyclosporine A did not affect matrix thermal properties. Altogether, our data provide a contribution towards an understanding of the complex interaction between PLLA and different drugs. Our results hold implications regarding the necessity of target-oriented thermal treatment to ensure the shelf life and performance of stent coatings. [ABSTRACT FROM AUTHOR]

The resorption rate of bioresorbable implants requires tuning to match the desired field of application. The use of Mg as implant material is highly advantageous, as it provides sufficient mechanical strength combined with its biodegradability. Consequently, the implant vanishes after it has served its intended purpose, allowing the complete restoration of natural tissue and organ function. However, a biodegradable Mg implant requires a biodegradable coating to slow the rate of Mg corrosion, as a permanent coating would negate the benefits of using Mg as an implant material. Therefore, degradable polymers are the materials of choice, especially polyester-based coatings, such as PLLA, as they have been proven in clinical practice over the long term. Within this work, the degradation retarding effect of a physical barrier in form of four clinically relevant polyester-based coatings, poly-l-lactide (PLLA), poly-l-lactide- co -glycolide (PLGA), poly(l-lactide- co -PEG) triblock copolymer (PLLA- co -PEG), and polydioxanone (PDO), is investigated in vitro under pH-static conditions using CO 2 gas to compensate pH changes due to Mg corrosion. Coating thicknesses of 7.5 to 8.3 μm were comparable to commercially available stent systems. Quantitative analysis of magnesium concentration in buffered test medium by a photometric assay allows real-time monitoring. Shielding effect of different polyesters through polymer coating and formation of a protective passivation layer beneath the polymer coating was observed and characterized using SEM and EDX techniques. Our finding was that even imperfect polymer layers provide a considerable protective effect, and the used in vitro setup matches reported in vivo observations regarding elemental composition of corrosion products.