title: Polymers and drugs suitable for the development of a drug delivery drainage system in glaucoma surgery.
abstract: 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.
authors: Institute for Biomedical Engineering, University of Rostock, Friedrich-Barnewitz-Str. 4, D-18119 Rostock, Germany. marian.loebler@uni-rostock.de
authors: Marian
authors: M
authors: Löbler
authors: Katrin
authors: K
authors: Sternberg
authors: Oliver
authors: O
authors: Stachs
authors: Reto
authors: R
authors: Allemann
authors: Niels
authors: N
authors: Grabow
authors: Anne
authors: A
authors: Roock
authors: Christine F
authors: CF
authors: Kreiner
authors: Detlef
authors: D
authors: Streufert
authors: Axel T
authors: AT
authors: Neffe
authors: Bui Duc
authors: BD
authors: Hanh
authors: Andreas
authors: A
authors: Lendlein
authors: Klaus-Peter
authors: KP
authors: Schmitz
authors: Rudolf
authors: R
authors: Guthoff
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D003315:Cornea / Q000166:cytology / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D005901:Glaucoma / Q000601:surgery*; D020327:Glaucoma Drainage Implants; D005938:Glucocorticoids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006885:Hydroxybutyrates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008422:Materials Testing; D051379:Mice; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits; D013314:Stress, Mechanical; D013499:Surface Properties; D013718:Tensile Strength; D014222:Triamcinolone Acetonide / Q000737:chemistry / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology; D000094122:Polyhydroxybutyrates
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D005938:Glucocorticoids; D006885:Hydroxybutyrates; D017239:Paclitaxel; D011091:Polyesters; D011108:Polymers; D014222:Triamcinolone Acetonide; D050257:Tubulin Modulators; C107955:poly(4-hydroxybutanoate); C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates