July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Chitosan coated Hyaluronic Acid Antibiotic Transport System (CHATS)
Author Affiliations & Notes
  • Margaret Hubbell
    Ophthalmology, Tulane University, New Orleans, Louisiana, United States
  • Mitchell Fullerton
    Ophthalmology, Tulane University, New Orleans, Louisiana, United States
  • Nurettin Sahiner
    Ophthalmology, Tulane University, New Orleans, Louisiana, United States
  • Sheila Horsley
    Texas Women's University, Texas, United States
  • Ze Zhang
    Ophthalmology, Tulane University, New Orleans, Louisiana, United States
  • Ramesh Ayyala
    Ophthalmology, University of South Florida, Florida, United States
    Ophthalmology, Tulane University, New Orleans, Louisiana, United States
  • Footnotes
    Commercial Relationships   Margaret Hubbell, None; Mitchell Fullerton, None; Nurettin Sahiner, None; Sheila Horsley, None; Ze Zhang, None; Ramesh Ayyala, None
  • Footnotes
    Support  Southern Eye Bank Research Grant
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5397. doi:
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    • Get Citation

      Margaret Hubbell, Mitchell Fullerton, Nurettin Sahiner, Sheila Horsley, Ze Zhang, Ramesh Ayyala; Chitosan coated Hyaluronic Acid Antibiotic Transport System (CHATS). Invest. Ophthalmol. Vis. Sci. 2019;60(9):5397.

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

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Purpose : Frequent applications of topical antibiotics is the standard treatment for ocular infections, for humans and marine mammals alike. Sustained release of antibiotics following a single application will improve the patient compliance and may lead to better treatment outcomes. Our group has successfully created Hyaluronic Acid (HA)-Antibiotic nanoparticles and demonstrated efficacy against common bacteria that lead to ocular infections. This system is useful for intraocular injections but could be optimized for ocular surface infections. Chitosan is a successfull mucoadhesive with bacteriostatic properties and a promising addition for topical application.

Methods : Chitosan was conjugated with HA-Antibiotic nanoparticles and delivered in suspension on the cornea and conjunctival surface of South Eye Bank eyes . pH was optimized. Cytotoxicity was assessed on whole cornea using OCT imaging of stroma and epithelium with measurements of epithelial thickness over time. To assess antimicrobial activity, polymers were suspended in various concentrations on agar plates previously plated with Pseudomonas, Ecoli, Staphylococcus or Methicilin-Resistant Staphylococcus Aureus (MRSA) and growth inhibition was measured in mm. Additional studies of antibiotic dose release with HPLC in tear solution are currently underweay.

Results : Chitosan-HA+Antibiotic nanoparticles adhered to the corneal surface for a minimum of 2 hours, significantly increasing adhesion. Optimization of pH to physiologic ranges was performed successfully and resulted in intact epithelium with statistically unchaged thickness on OCT as compared with controls. HA-Ciprofloxacin and HA-Vancomycin nanoparticles demonstrated effective inhibition of Pseudomonas and MRSA. Conjugation of Chitosan to the exterior versus interior of the nanoparticle affected the antimicrobial efficacy and is undergoing optimization.

Conclusions : Clinical outcome and patient quality of life would benefit from a sustained release antibiotic that could be administered less frequently to treat complicated corneal infections. Our HA-antibiotic polymers have been shown to release the necessary antibiotic concentration for antimicrobial growth inhibition. Conjugating Chitosan to these polymers increased binding to corneal and conjunctival tissue, sustaining delivery of antibiotics. This study demonstrates these polymers are biocompatible with human corneal tissue and achieve MIC antibiotic concentrations.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.




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