Assessment of the in vitro efficacy of 5-aminolevulinic acid in combination with methotrexate: A potential new therapy for the treatment of psoriasis

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dc.contributor.advisorHass, Martha A.
dc.contributor.advisorVoigt, Jeffrey
dc.contributor.authorQuirk, Mackenzie '22
dc.contributor.committeememberDearborn, Richard E.
dc.date.accessioned2023-04-20T17:48:04Z
dc.date.available2023-04-20T17:48:04Z
dc.date.issued2022-08
dc.descriptionClick on the Resource Link to find this item in the ACPHS Library catalog.
dc.description.abstractPsoriasis is broadly defined as a chronic skin disease marked by raised, itchy scales that can be expressed anywhere but are most found on the knees, elbows, trunk, and scalp. Patients with moderate to severe plaque psoriasis experience physical discomfort in addition to higher levels of anxiety, depression, bullying, and lower employment opportunities than people with healthy skin. There are two main contributors to the development and prolongation of the disease: T-cell activation and recruitment resulting in chronic inflammation, and the hyperproliferation of keratinocytes to form thick, scaly plaques. Current drug therapy targets one or both mechanisms of pathophysiology. This project focused on the potential therapeutic benefits of combining the antiproliferative agent methotrexate (MTX) with the photosensitizing agent 5-aminolevulinic acid (ALA) in an in vitro model for plaque psoriasis using HaCaT cells. To determine the effect of protoporphyrin IX (PpIX) generation, cells were treated with either ALA alone, MTX alone, or a 1:1 molar combination of ALA + MTX at a concentration range of 0.1 \342\200\223 1 mM. Absorbance was measured using fluorescent spectroscopy. To determine the clinical effect of PpIX induced phototoxicity, treated cells were irradiated with blue light and cell viability was assessed using an MTT assay. To assess the antiproliferative effect of drug treatment at a range of 2 \342\200\223 100 nM, a dihydrofolic reductase (DHFR) enzyme inhibition assay was used. The results suggest that MTX does not affect the ability of ALA to cause a dose-dependent increase in PpIX generation. Additionally, blue light irradiation in cells treated with ALA alone or in combination causes significant cytotoxicity compared to cells not exposed to blue light, indicating that MTX does not impede the ability of ALA-induced PpIX production to cause phototoxicity. The DHFR assay demonstrated that ALA does not impair the ability of MTX to inhibit DHFR. In summary, the combination of ALA and MTX provides two mechanisms of action against an in vitro model of psoriasis without either compound interfering with the mechanism of the other, suggesting that the combination of these agents would be feasible and warrants further investigation with in vivo models.
dc.description.degreeMS in Pharmaceutical Sciences
dc.description.urihttps://acphs.on.worldcat.org/oclc/1348105129
dc.format.extent77 pages
dc.identifier.citationQuirk M. Assessment of the in vitro efficacy of 5-aminolevulinic acid in combination with methotrexate: a potential new therapy for the treatment of psoriasis [thesis]. Ann Arbor (MI): Proquest LLC; 2022. 77 p.
dc.identifier.thesis29328023
dc.identifier.urihttps://hdl.handle.net/20.500.14303/48
dc.languageen_US
dc.publisherProquest LLC
dc.relation.ispartofAlbany College of Pharmacy and Health Sciences Theses
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dc.subjectaminolevulinic
dc.subjecthacat
dc.subjectin vitro
dc.subjectmethotrexate
dc.subjectphotodynamic light therapy
dc.subjectpsoriasis
dc.titleAssessment of the in vitro efficacy of 5-aminolevulinic acid in combination with methotrexate: A potential new therapy for the treatment of psoriasis
dc.typeThesis
local.departmentprogramDepartment of Pharmaceutical Sciences
local.departmentprogramDepartment of Life Sciences
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Hass, Martha Theses Advised