July 2018
Volume 59, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2018
Drug eluting dendrimer-hyaluronic acid nanoglue sealants to minimize corneal sutures
Author Affiliations & Notes
  • Siva Pramodh Kambhampati
    Center for Nanomedicine at Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Uri Soiberman
    Center for Nanomedicine at Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Tony P Wu
    Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
    Center for Nanomedicine at Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Abdul Elah Al Towerki
    Opthalmology, King Khaled Eye Specialist Hospital, Riyadh, Riyadh, Saudi Arabia
  • Walter Stark
    Center for Nanomedicine at Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Samuel C Yiu
    Center for Nanomedicine at Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Kannan Rangaramanujam
    Center for Nanomedicine at Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Siva Pramodh Kambhampati, None; Uri Soiberman, None; Tony Wu, None; Abdul Elah Al Towerki, None; Walter Stark, None; Samuel Yiu, None; Kannan Rangaramanujam, Ashvattha Therapeutics (P)
  • Footnotes
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Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4422. doi:
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      Siva Pramodh Kambhampati, Uri Soiberman, Tony P Wu, Abdul Elah Al Towerki, Walter Stark, Samuel C Yiu, Kannan Rangaramanujam; Drug eluting dendrimer-hyaluronic acid nanoglue sealants to minimize corneal sutures. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4422.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Corneal sutures increase the risk of post-surgical astigmatism, inflammation and neovascularization, and bacterial keratitis. Hence, novel interventions that obviate the need for sutures are highly desirable. Additionally, topical antibiotics and steroids are commonly used after corneal and cataract surgery. Our aim is to develop a novel, multi-functional, in situ photocurable, dendrimer-hyaluronic acid nanoglue equipped with localized drug release for rapid sealing of corneal incisions, promoting corneal wound healing, and localized, targeted treatment of post-surgical inflammation.

Methods : The photo-crosslinkable dendrimers-dexamethasone conjugates and hyaluronic acid components of the nanoglue were synthesized using multiple step reactions. The sealing capacity of the nanoglue for different incisions was assessed ex vivo in freshly enucleated rabbit eyes using a custom-made infusion system. In vivo studies were conducted in rat model of corneal laceration and transplantation. A 3-mm central corneal wound was created in rat corneas using a 3mm surgical keratome, then either sealed with the nanoglue or sutured with 10-0 nylon. Anterior chamber depth, corneal scarring, and signs of infection were assessed by clinical observations on post-operative days (POD) 1, 3, 7, 14, and 30. Wound architecture was evaluated with anterior segment optical coherence tomography (OCT). Immunohistochemistry (IHC) was utilized to demonstrate the degree of inflammation, scarring, and would healing.

Results : The photo cross-linked nanoglue seals the corneal incisions rapidly, and it withstands higher intraocular pressures compared to sutures. The in vivo study showed that although both nanoglue and suture were effective in wound closure, corneal scarring was milder in the nanoglue group. OCT demonstrated better wound edge approximation in the nanoglue group, compared to the sutured group. IHC studies suggest that nanoglue accelerates wound healing with no signs of inflammation and neovascularization in and around the wound area. In contrast sutures showed neovascularization and inflammation.

Conclusions : Our studies suggest that the novel drug eluting nanoglue has better sealing properties compared to sutures and promotes wound healing with minimal corneal scarring. These results suggest that dendrimer based nanoglue with localized drug release may become an important tool in the armamentarium of the corneal surgeon.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

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