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Poly(ethylene glycol) hydrogels for sustained topical drug delivery to the eyes and skin
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Poly(ethylene glycol) hydrogels for sustained topical drug delivery to the eyes and skin
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ETD_2388
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000052096
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eng
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theses
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Pharmaceutical Science
Subject
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(authority = ETD-LCSH)
Topic
Polymeric drug delivery systems
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Ocular pharmacology
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Therapeutics, Ophthalmological
Subject
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(authority = ETD-LCSH)
Topic
Transdermal medication
Abstract
Sulfur mustard (SM) is a potent chemical warfare agent that mainly affects the eyes, lungs and skin. Inflammatory cytokines and Matrix Metalloproteinase-9 (MMP-9) have been identified as potential therapeutic targets for SM-induced tissue damage since they quantitatively increase over time in response to SM exposure. Doxycycline is a tetracycline antibiotic with anti-inflammatory properties that acts by inhibiting MMP-9. Currently, neither doxycycline nor doxycycline delivery systems have been investigated for treatment of SM injuries.
The objective of this thesis project is to design and fabricate sustained release topical doxycycline delivery systems and evaluate their wound healing efficacy. Fast forming hydrogels were prepared by crosslinking a poly(ethylene glycol) (PEG)-based polymer containing multiple thiol groups with different polymers or crosslinkers. The optical properties of the hydrogels were evaluated by spectrophotometry and the hydrogels that were transparent or close to transparent were chosen for drug delivery to the eye. Physicochemical properties of the hydrogels evaluated by rheometry and swelling kinetics show that the hydrogels have good mechanical strength with a low degree of swelling (<8%).
In vitro release profiles of doxycycline-loaded hydrogels demonstrated biphasic release with an initial burst phase followed by a sustained phase. Permeation of doxycycline through vesicant wounded corneas was 2.5 to 3.4 fold higher than through unwounded corneas suggesting that the barrier function of the cornea is compromised after vesicant exposure. Doxycycline hydrogels showed a significant improvement in corneal epithelial healing compared to a similar dose of doxycycline solution in a vesicant-exposed rabbit corneal organ culture model.
The model vesicant, nitrogen mustard (NM) showed dose and time dependent wound progression in SKH-1 mice. The permeability of NM-exposed skin (5 µmoles) to different molecular markers increased significantly compared to the control suggesting that stratum corneum does not act as a barrier for transdermal drug absorption after vesicant exposure. From histology analyses, it is evident that doxycycline hydrogel treated groups showed significant wound healing efficacy compared to untreated or placebo hydrogel treated groups. In summary, in situ forming topical doxycycline-loaded PEG hydrogels showed superior wound healing efficacy offering a potential therapeutic option for mustard injuries in the eye and skin.
The objective of this thesis project is to design and fabricate sustained release topical doxycycline delivery systems and evaluate their wound healing efficacy. Fast forming hydrogels were prepared by crosslinking a poly(ethylene glycol) (PEG)-based polymer containing multiple thiol groups with different polymers or crosslinkers. The optical properties of the hydrogels were evaluated by spectrophotometry and the hydrogels that were transparent or close to transparent were chosen for drug delivery to the eye. Physicochemical properties of the hydrogels evaluated by rheometry and swelling kinetics show that the hydrogels have good mechanical strength with a low degree of swelling (<8%).
In vitro release profiles of doxycycline-loaded hydrogels demonstrated biphasic release with an initial burst phase followed by a sustained phase. Permeation of doxycycline through vesicant wounded corneas was 2.5 to 3.4 fold higher than through unwounded corneas suggesting that the barrier function of the cornea is compromised after vesicant exposure. Doxycycline hydrogels showed a significant improvement in corneal epithelial healing compared to a similar dose of doxycycline solution in a vesicant-exposed rabbit corneal organ culture model.
The model vesicant, nitrogen mustard (NM) showed dose and time dependent wound progression in SKH-1 mice. The permeability of NM-exposed skin (5 µmoles) to different molecular markers increased significantly compared to the control suggesting that stratum corneum does not act as a barrier for transdermal drug absorption after vesicant exposure. From histology analyses, it is evident that doxycycline hydrogel treated groups showed significant wound healing efficacy compared to untreated or placebo hydrogel treated groups. In summary, in situ forming topical doxycycline-loaded PEG hydrogels showed superior wound healing efficacy offering a potential therapeutic option for mustard injuries in the eye and skin.
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electronic resource
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xvii, 188 p. : ill.
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Ph.D.
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Includes bibliographical references (p. 166-187)
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by Siva Naga Sree Priya Anumolu
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Anumolu
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Siva Naga Sree Priya
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1981-
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Siva Naga Sree Priya Anumolu
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Sinko
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Patrick
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chair
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Patrick J Sinko
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Stein
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Stanley
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Stanley Stein
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Michniak
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Bozena
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Bozena Michniak
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Laskin
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Jeffrey
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Jeffrey Laskin
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Rutgers University
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Graduate School - New Brunswick
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2010
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2010-01
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xx
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Rutgers University Electronic Theses and Dissertations
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Graduate School - New Brunswick Electronic Theses and Dissertations
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doi:10.7282/T3736R31
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ETD doctoral
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Rights
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The author owns the copyright to this work.
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Copyright protected
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Open
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Permission or license
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Anumolu
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Siva Naga
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2010-01-05 12:44:51
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Siva Naga Anumolu
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Rutgers University. Graduate School - New Brunswick
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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185 days
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