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2016 OMIG Abstract 12

Antimicrobial Silk Ocular Drug Delivery Implant for
Chronic Posterior Segment Diseases

Irmgard Behlau, Biplab Sarkar, Chiara Ghezzi, Ricardo Louzada, Jay Duker, David Kaplan
Tufts University School of Medicine, Tufts Medical School, Ophthalmology, Biomedical Engineering, and Molecular Biology & Microbiology, Boston and Medford, MA USA

Purpose:  Development of a safe, refillable, long-term silk-based drug delivery implant with a greatly diminished risk for infection. The silk-based implant will be permanently coated with a non-leaching antimicrobial N,N-hexyl, methyl polyethylenimine (HMPEI) ‘spikey polymer’, which kills by a contact-dependent mechanism with effectiveness over a broad host range of enveloped viruses, bacteria, and fungi. 

Methods: The silk implant will have three design features: 1) small gauge self-sealing refillable injection port, impermeable delivery channel, and permeable intravitreal drug reservoir that should release anti-VEGF (bevacizumab) over three months. We have made several silk derivatives to maximize the degree of HMPEI bound silk surface area, host cell biocompatibility, and achieve the greatest antimicrobial efficacy. 

Results: We were able to successfully design the implant incorporating three very different functions, manufactured as one piece, made entirely out of silk. We have been able to successfully attach the antimicrobial HMPEI coating to the silk implant. Pharmacokinetics, biocompatibility and microbial colonization studies in pigmented Dutch-belted rabbits are in progress. At one month, the antimicrobial coated silk based implant appears to be well tolerated in the posterior segment of the eye. 

Conclusions:  The development of non-antibiotic approaches to safeguard implanted ophthalmic and medical devices is very much needed. The antimicrobial HMPEI-silk ocular implant would provide optimal and safe delivery of long-term medication that will be comfortable, decrease the number of outpatient visits, and be relatively less costly. This technology may prove not only sight-saving, but cost-saving in prevention of blindness involving the retina with applicability to other diseases that occur in body sites that limit penetration of medication. 

Disclosures:  None
Grant Support: DoD USAMRMC 

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