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Antifibrotic treatment during glaucoma surgery leads to an improved outcome for patients. Drug delivery systems for placement under the subconjuctiva after surgery made of cyclodextrins and crosslinked with Epichlorohydin were loaded with Josamycin and tested in vivo. After subconjunctival application in three New Zealand White rabbits, blood samples were taken by the means of Mitra devices at defined time points. Determination of blood levels of Josamycin was performed using liquid chromatography mass spectrometry. Detection of Josamycin was achieved during 48 h suggesting a sustained release over the course of this study.

Glaucoma is the leading cause of blindness worldwide. However, its surgical treatment, in particular via trabeculectomy, can be complicated by fibrosis. In current clinical practice, application of the drug, Mitomycin C, prevents or delays fibrosis, but can lead to additional side effects, such as bleb leakage and hypotony. Previous in silico drug screening and in vitro testing has identified the known antibiotic, josamycin, as a possible alternative antifibrotic medication with potentially fewer side effects. However, a suitable ocular delivery mechanism for the hydrophobic drug to the surgical site does not yet exist. Therefore, the focus of this paper is the development of an implantable drug delivery system for sustained delivery of josamycin after glaucoma surgery based on crosslinked γ-cyclodextrin. γ-Cyclodextrin is a commonly used solubilizer which was shown to complex with josamycin, drastically increasing the drug's solubility in aqueous solutions. A simple γ-cyclodextrin crosslinking method produced biocompatible hydrogels well-suited for implantation. The crosslinked γ − cyclodextrin retained the ability to form complexes with josamycin, resulting in a 4-fold higher drug loading efficiency when compared to linear dextran hydrogels, and prolonged drug release over 4 days. [ABSTRACT FROM AUTHOR]