An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection

Abstract There are numerous barriers to achieving effective intraocular drug administration, including the mucus layer protecting the ocular surface. For this reason, antibiotic eye drops must be used multiple times per day to prevent and treat ocular infections. Frequent eye drop use is inconvenien...

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Main Authors: Aditya Josyula, Revaz Omiadze, Kunal Parikh, Pranjali Kanvinde, Matthew B. Appell, Pratikkumar Patel, Hiwa Saeed, Yogesh Sutar, Nicole Anders, Ping He, Peter J. McDonnell, Justin Hanes, Abhijit A. Date, Laura M. Ensign
Format: Article
Language:English
Published: Wiley 2021-09-01
Series:Bioengineering & Translational Medicine
Subjects:
Online Access:https://doi.org/10.1002/btm2.10238
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author Aditya Josyula
Revaz Omiadze
Kunal Parikh
Pranjali Kanvinde
Matthew B. Appell
Pratikkumar Patel
Hiwa Saeed
Yogesh Sutar
Nicole Anders
Ping He
Peter J. McDonnell
Justin Hanes
Abhijit A. Date
Laura M. Ensign
author_facet Aditya Josyula
Revaz Omiadze
Kunal Parikh
Pranjali Kanvinde
Matthew B. Appell
Pratikkumar Patel
Hiwa Saeed
Yogesh Sutar
Nicole Anders
Ping He
Peter J. McDonnell
Justin Hanes
Abhijit A. Date
Laura M. Ensign
author_sort Aditya Josyula
collection DOAJ
description Abstract There are numerous barriers to achieving effective intraocular drug administration, including the mucus layer protecting the ocular surface. For this reason, antibiotic eye drops must be used multiple times per day to prevent and treat ocular infections. Frequent eye drop use is inconvenient for patients, and lack of adherence to prescribed dosing regimens limits treatment efficacy and contributes to antibiotic resistance. Here, we describe an ion‐pairing approach used to create an insoluble moxifloxacin–pamoate (MOX–PAM) complex for formulation into mucus‐penetrating nanosuspension eye drops (MOX–PAM NS). The MOX–PAM NS provided a significant increase in ocular drug absorption, as measured by the area under the curve in cornea tissue and aqueous humor, compared to Vigamox in healthy rats. Prophylactic and treatment efficacy were evaluated in a rat model of ocular Staphylococcus aureus infection. A single drop of MOX–PAM NS was more effective than Vigamox, and completely prevented infection. Once a day dosing with MOX–PAM NS was similar, if not more effective, than three times a day dosing with Vigamox for treating S. aureus infection. The MOX–PAM NS provided increased intraocular antibiotic absorption and improved prevention and treatment of ocular keratitis, and the formulation approach is highly translational and clinically relevant.
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spelling doaj.art-53f65d7dc2de46cba1cb8c3427acb6692022-12-21T18:40:32ZengWileyBioengineering & Translational Medicine2380-67612021-09-0163n/an/a10.1002/btm2.10238An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infectionAditya Josyula0Revaz Omiadze1Kunal Parikh2Pranjali Kanvinde3Matthew B. Appell4Pratikkumar Patel5Hiwa Saeed6Yogesh Sutar7Nicole Anders8Ping He9Peter J. McDonnell10Justin Hanes11Abhijit A. Date12Laura M. Ensign13The Center for Nanomedicine, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Center for Nanomedicine, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Center for Nanomedicine, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Center for Nanomedicine, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Center for Nanomedicine, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USADepartment of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy University of Hawaii Hilo Hawaii USADepartment of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy University of Hawaii Hilo Hawaii USADepartment of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy University of Hawaii Hilo Hawaii USAThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University Baltimore Maryland USAThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University Baltimore Maryland USADepartment of Ophthalmology, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Center for Nanomedicine, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Center for Nanomedicine, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USAThe Center for Nanomedicine, The Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore Maryland USAAbstract There are numerous barriers to achieving effective intraocular drug administration, including the mucus layer protecting the ocular surface. For this reason, antibiotic eye drops must be used multiple times per day to prevent and treat ocular infections. Frequent eye drop use is inconvenient for patients, and lack of adherence to prescribed dosing regimens limits treatment efficacy and contributes to antibiotic resistance. Here, we describe an ion‐pairing approach used to create an insoluble moxifloxacin–pamoate (MOX–PAM) complex for formulation into mucus‐penetrating nanosuspension eye drops (MOX–PAM NS). The MOX–PAM NS provided a significant increase in ocular drug absorption, as measured by the area under the curve in cornea tissue and aqueous humor, compared to Vigamox in healthy rats. Prophylactic and treatment efficacy were evaluated in a rat model of ocular Staphylococcus aureus infection. A single drop of MOX–PAM NS was more effective than Vigamox, and completely prevented infection. Once a day dosing with MOX–PAM NS was similar, if not more effective, than three times a day dosing with Vigamox for treating S. aureus infection. The MOX–PAM NS provided increased intraocular antibiotic absorption and improved prevention and treatment of ocular keratitis, and the formulation approach is highly translational and clinically relevant.https://doi.org/10.1002/btm2.10238antibioticconjunctivitiseye dropkeratitismucoinertmucus‐penetrating particles
spellingShingle Aditya Josyula
Revaz Omiadze
Kunal Parikh
Pranjali Kanvinde
Matthew B. Appell
Pratikkumar Patel
Hiwa Saeed
Yogesh Sutar
Nicole Anders
Ping He
Peter J. McDonnell
Justin Hanes
Abhijit A. Date
Laura M. Ensign
An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection
Bioengineering & Translational Medicine
antibiotic
conjunctivitis
eye drop
keratitis
mucoinert
mucus‐penetrating particles
title An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection
title_full An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection
title_fullStr An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection
title_full_unstemmed An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection
title_short An ion‐paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection
title_sort ion paired moxifloxacin nanosuspension eye drop provides improved prevention and treatment of ocular infection
topic antibiotic
conjunctivitis
eye drop
keratitis
mucoinert
mucus‐penetrating particles
url https://doi.org/10.1002/btm2.10238
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