June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
OcuSurfTM-Mediated Antimicrobial Therapies to Treat Multi-Drug Resistant Ocular Infections
Author Affiliations & Notes
  • Kevin L Ward
    Formulations, Integral BioSystems, Bedford, Massachusetts, United States
  • Shikha P Barman
    Executive, Integral Biosystems LLC, Bedford, Massachusetts, United States
  • Koushik Barman
    Formulations, Integral BioSystems, Bedford, Massachusetts, United States
  • Anne-Marie Cromwick
    Formulations, Integral BioSystems, Bedford, Massachusetts, United States
  • Kathryn S Crawford
    PharmOcu, Andover, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Kevin Ward, Integral Biosystems LLC (E), Integral Biosystems LLC (P); Shikha Barman, Integral Biosystems LLC (I), Integral Biosystems LLC (P); Koushik Barman, Integral BioSystems (P), Integral Biosystems LLC (E); Anne-Marie Cromwick, Integral BioSystems (E), Integral BioSystems (P); Kathryn Crawford, Integral BioSystems (C)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1084. doi:
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      Kevin L Ward, Shikha P Barman, Koushik Barman, Anne-Marie Cromwick, Kathryn S Crawford; OcuSurfTM-Mediated Antimicrobial Therapies to Treat Multi-Drug Resistant Ocular Infections. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1084.

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

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Abstract

Purpose : The past two decades have seen an increase in antibiotic resistance among bacterial pathogens in the eye. Ocular staphylococci have developed resistance to methicillin and other antibiotic classes. We have previously presented OcuSurf™: a delivery system that has been designed for rapid and efficient absorption into tissues. Eye-drop formulations utilize insoluble active pharmaceutical ingredients; thus, they exist as drug suspensions, which need to dissolve before they can be absorbed. In the ocular space, rapid fluid turnover and loss via the naso-lacrimal duct results in just 5% of the drug being absorbed. Thus, clinical need exists for a drug delivery system that can rapidly permeate and adhere to tissues for enhanced bioavailability and enhanced duration of therapeutic levels of drug. We have developed stable OcuSurf-mediated formulations of Besifloxacin and Vancomycin. Comparative in-vitro susceptibility (MIC) and time-kill experiments of these formulations against multi-drug resistant clinical bacterial isolates of s. aureus and p. aeroginosa were performed, Stability, in-vitro release, corneal permeability and in-vitro irritation studies were performed to select the best drug product candidate.

Methods : Permeability studies were performed through freshly excised corneal membranes, using Franz-type diffusion cells and permeated drug was quantitated by HPLC. Irritation assessment of the formulations was performed in a standard Epiocular model using corneal cell constructs, using 120 minute incubation of the formulations. Physicochemical characterization was performed, including stability assessments by HPLC.

Results : Of the drugs tested, OcuSurf-formulated Vancomycin and Besifloxacin showed low MIC (<1 microgram/mL) against drug resistant strains of MRSA and MSSA. High corneal permeability of both drugs were observed (10-15% of drug permeated through 22 hours) and fast in-vitro release (30-40%) demonstrating high potential for rapidly absorbing formulations tested in-vivo. The formulations were of mean size range 0.250-0.300 nm and demonstrated a liquid crystalline internal microstructure. The formulations were stable at 3 months and were non-irritating by Epiocular testing.

Conclusions : Antimicrobial formulations to treat drug-resistant ocular infections are feasible.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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