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Moxifloxacin Loaded Ophthalmic Inserts for Prophylaxis of Endophthalmitis

Li, Huatian (2021) Moxifloxacin Loaded Ophthalmic Inserts for Prophylaxis of Endophthalmitis. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Endophthalmitis is an inflammatory disorder that usually occurs in intraocular fluids or tissues involving vitreous and/or aqueous humors. It can be caused by bacterial, fungal, or other infecting microorganisms spreading from either inside or outside the body. As a serious eye disease, it is very likely to cause devastating consequences including irreversible vision loss even with prompt diagnosis and treatment. Endophthalmitis is a rare disease. The overall incidence rates of endophthalmitis are reported to be between 0.04% to 0.4%, but it remains a challenge to prevent the development of this disease. Moxifloxacin (MOX) is a broad spectrum, fourth-generation fluoroquinolone, and has been commonly used for prophylaxis of endophthalmitis. MOX is available as eyedrops, tablet and ocular injection, but they all have limitations such as low patient compliance, poor bioavailability and invasive administration route with potential risks. To address these problems, we proposed a moxifloxacin loaded, sustained-release ophthalmic insert that could deliver the drug locally and non-invasively for up to 24 h in vivo. In this study, we identified Eudragit® FS30D and Eudragit® EPO in ratio of 80%-20% as the optimal formulation of insert. The 10 mm inserts demonstrated a drug loading efficiency above 80%. Insert prepared with optimized formulation achieved a sustained release of MOX for 8 hours in vitro, and demonstrated good stability upon storage at 45℃, 75% relative humidity (RH), 25℃, 60% RH and 4℃. Meanwhile, a UPLC method for analysis of MOX was developed and validated in this study as well, which could be further optimized for analysis of MOX degradation in inserts. In vitro study showed that MOX loaded inserts were active against Staphylococcus aureus and Escherichia coli and placebo inserts were non-toxic to human corneal limbal epithelial (HCLE) cells. Using a rabbit endophthalmitis model, the in vivo study showed that the prophylactic efficacy of MOX loaded insert was comparable with Vigamox® (0.5% moxifloxacin) eyedrop on a rabbit endophthalmitis model. In conclusion, we developed a moxifloxacin loaded ophthalmic insert that achieved a sustained release of drug for 8 hours and was non-toxic to HCLE cell. The insert also demonstrated satisfactory stability, promising anti-bacterial activity in vitro and prophylactic efficacy against endophthalmitis in vivo. This study was a good “proof of concept” that ophthalmic insert could be a potential platform for ocular sustained release.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Li, Huatianhul63@pitt.eduhul63
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSant, Vinayakvis45@pitt.eduvis45
Committee MemberRohan, Lisa Crohanl@pitt.edurohanl
Committee MemberLi, Songsol4@pitt.edusol4
Date: 6 May 2021
Date Type: Publication
Defense Date: 9 April 2021
Approval Date: 6 May 2021
Submission Date: 21 April 2021
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 91
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Endophthalmitis;Ophthalmic insert;Moxifloxacin;Prophylaxis
Date Deposited: 06 May 2021 16:33
Last Modified: 06 May 2021 16:33
URI: http://d-scholarship.pitt.edu/id/eprint/40716

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