A multifunctional bilayered microstent as glaucoma drainage device.

Commercial non-degradable glaucoma implants are often associated with undesired hypotony, fibrosis, long term failure, and damage of adjacent tissues, which may be overcome by a multifunctional polymeric microstent for suprachoroidal drainage. This study reports the design and fabrication of such devices with tailorable internal diameters (50-300 µm) by solvent-free, continuous hot melt extrusion from blends of poly[(ε-caprolactone)-co-glycolide] and poly(ε-caprolactone) [PCL]. A spatially directed release was supported by bilayered microstents with an internal drug-free PCL layer, and a quantitative description of release kinetics with diclofenac sodium as model drug was provided. Furthermore, the slow degradation pattern (> 1 year) was analyzed and potential effects of 1-5 wt.% drug loading on material properties were excluded. Translational aspects including sterilization by γ-irradiation on dry ice, in vitro biocompatibility, and in vivo implantation were addressed. The promising results support further functional analysis of long-term in vivo performance and suppression of disadvantageous capsule formation.

Polymers and drugs suitable for the development of a drug delivery drainage system in glaucoma surgery.

Implantation of a glaucoma drainage system is an appropriate therapeutic intervention in some glaucoma patients. However, one drawback with this approach is the fibrotic tissue response to the implant material, leading to reduced flow of aqueous liquid or complete blockage of the drainage system. As a basis for developing an aqueous shunt we report here investigations with poly(3-hydroxybutyrate) (P(3HB)) and poly(4-hydroxybutyrate) (P(4HB)) as polymer matrices and with paclitaxel (PTX) and triamcinolone acetonide (TA) as drugs that might, in combination, delay or prevent the process of fibrosis by reducing fibroblast activity. P(3HB) and P(4HB) were fabricated into test prototypes with 500 µm outer and 200 µm inner diameter and ∼1 cm length. The antiproliferative agent PTX and the anti-inflammatory agent TA were incorporated into the polymer matrices and were released by diffusion. In vitro cell assays demonstrated that the polymers have the potential to reduce fibroblast viability, while TA showed differential inhibition of Tenon fibroblasts, but not cornea keratocytes. Implantation of polymer disks and prototype devices into rabbit eyes confirmed the good biocompatibility of the materials. The combined use of a poly(hydroxybutyrate) polymer with PTX or TA has the potential to reduce the fibrosis associated with conventional glaucoma drainage systems.

A new FTIR-ATR cell for drug diffusion studies.

The drug diffusion of most compounds, particularly hydrophilic molecules through the skin is limited by the permeation of the outermost cell layers of the epidermis, the stratum corneum(SC). For this reason it is of interest to characterize drug diffusion processes through this skin layer. A new FTIR-ATR cell was developed for non-invasive real time measurements of drug diffusion. The diffusion of water through an artificial polyethyleneglycol-polydimethylsiloxane membrane was studied. Additionally the diffusion of urea in human SC was analyzed. Based on a mathematical model the diffusion coefficients were derived. We could reveal that this cell associates the advantages of the Franz diffusion cell and the FTIR-ATR spectroscopy as a new powerful method for determining drug diffusion through biological membranes.