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2018 Agenda and Abstracts | < Previous Next >

2018 OMIG Abstract

Long-term Antimicrobial Silk-based Drug Delivery Implant for the Posterior Segment

Irmgard Behlau, MD1,2,5, Chiara Ghezzi3, Harris K. Liu4, Biplab Sarkar3, Ricardo Louzada2, Jay S. Duker2, Alexander M. Klibanov4, Nora Laver2, and David Kaplan3
1Molecular Biology & Microbiology, 2Ophthalmology, 3Biomedical Engineering, 4Tufts Univ. School of Medicine/Tufts Medical School, Boston, Medford, MA and Chemistry, 5MIT, Cambridge, MA, Infectious Diseases, Mt. Auburn Hospital, Cambridge, MA


Purpose: Development of a safe, refillable, long-term antimicrobial silk-based drug delivery implant for large molecules with a greatly diminished risk for infection.

Methods: Optimized method of covalent attachment of a non-leaching, antimicrobial N,N-hexyl, methyl polyethylenimine (HMPEI) to a permeable functionalized silk fibroin. Severalsilkderivatives were evaluated to maximize the degree of HMPEI bound silk surface area, host cell biocompatibility, and antimicrobial efficacy. Several implant design features were explored to maximize drug delivery, strength and ease of manufacturing. In vitro and in vivo rabbit pharmacokinetic studies andOCT evaluation of VEGF/anti-VEGF efficacy study was performed Histopathology was done on all explanted in vivo eyes.

Results: We successfully optimized the covalent attachment of HMPEI by functionalized silk tyrosine side chains. We gel-spun a continuous channel, created a fish-shaped implant which enablesone-step manufacturing and provides structural integrity, a smooth refillable channel, and enables sutureless implantation. Anti-VEGF HMPEI-silk drug delivery implant system in normal pigmented rabbit models in vivo showed minimal cellular reactivity and neovascularization at the surgical incision site only, and no inflammatory response surrounding the HMPEI-implant. There was a time-dependent fibroblastic response with progressive ingrowth of epithelial and stromal cells into the porous HMPEI - silk fibroin implants over 3 months and 9 months. There was no sign of infections in vivo.

Conclusion: We were successful in the design and in vitro pharmacokinetics studies of the silk-based anti-VEGF drug delivery device, the development of an antimicrobial, HMPEIderivatized intraocular silk drug delivery implant, the assessment of the anti-VEGF HMPEI-silk drug delivery implant system in normal pigmented rabbit models and in a diabetic retinopathy rabbit models in vivo. This is the first long-term antimicrobial silk-based drug delivery intraocular system that has been shown to be safe, well tolerated, and free of infection with broad applicability to other implantable medical devices.

Disclosure: N

Funding: DoD CDMRP


2018 Agenda and Abstracts | < Previous Next >