title: Simulation of drug distribution in the vitreous body after local drug application into intact vitreous body and in progress of posterior vitreous detachment.
abstract: Intravitreal injections and drug-loaded implants are current approaches to treat diseases of the posterior eye. To investigate the release of active agents and their distribution in the vitreous body, a new test system was developed that enables a realistic simulation of eye motions. It is called the eye movement system (EyeMoS). In combination with a previously developed model containing a polyacrylamide gel as a substitute for the vitreous body, this new system enables the characterization of the influence of eye motions on drug distribution within the vitreous body. In the presented work, the distribution of fluorescence-tagged model drugs of different molecular weight within the simulated vitreous was examined under movement with the EyeMoS and without movement. By replacing a part of the gel in the simulated vitreous body with buffer, the influence of the progress of posterior vitreous detachment (PVD) on the distribution of these model substances was also studied. The results indicate that convective forces may be of predominate influence on initial drug distribution. The impact of these forces on drug transport increases with simulated progression of PVD. Using the EyeMoS, the investigation of release and distribution from intravitreal drug delivery systems becomes feasible under biorelevant conditions.
authors: Institute of Pharmacy, Center of Drug Absorption and Transport, EMA University of Greifswald, Greifswald, 17487, Germany.
authors: Christian
authors: C
authors: Loch
authors: Malte
authors: M
authors: Bogdahn
authors: Sandra
authors: S
authors: Stein
authors: Stefan
authors: S
authors: Nagel
authors: Rudolf
authors: R
authors: Guthoff
authors: Werner
authors: W
authors: Weitschies
authors: Anne
authors: A
authors: Seidlitz
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D000906:Antibodies / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D018450:Disease Progression; D005133:Eye Movements; D058449:Intravitreal Injections; D008953:Models, Anatomic; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011698:Pursuit, Smooth; D012438:Saccades; D012995:Solubility; D014822:Vitreous Body / Q000187:drug effects* / Q000378:metabolism*; D020255:Vitreous Detachment / Q000378:metabolism*; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D003907:Dexamethasone; D004364:Pharmaceutical Preparations; D000099166:Polyacrylamides
keywords: diffusion; distribution; drug transport; eye movement system; hydrogels; in vitro model; intravitreal injection; posterior vitreous detachment; vitreous body; vitreous model