Assessment of Hydrolysis of Prodrugs and Co-drugs Derived from 5-Aminolevulinic Acid and Mycophenolic Acid

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dc.contributor.advisorHass, Martha A.
dc.contributor.authorStrumski, Kaitlyn '23
dc.contributor.committeememberLewis, L. Michelle
dc.contributor.committeememberShah, Manish
dc.date.accessioned2024-01-09T16:38:26Z
dc.date.available2024-01-09T16:38:26Z
dc.date.issued2023-08
dc.descriptionClick on the Resource Link to find this item in the ACPHS Library catalog.
dc.description.abstractMycophenolic acid (MPA) and 5-aminolevulenic acid (ALA) have been known to reduce the symptoms associated with autoimmune skin disease, psoriasis. It is hypothesized that the combination of these two drugs, when delivered simultaneously to the skin, will provide synergistic therapeutic benefit in suppressing the symptoms of psoriasis. This research project aims to evaluate the in vitro efficacy of prodrugs and investigational co-drugs derived from ALA and MPA using an immortalized human keratinocyte cell line (HaCaT) as models for drug behavior in human skin. Previously, it was shown that MPA and ALA do not negatively interact, but rather improve treatment when administered together. This project is specifically aimed at using HaCaT cells as a viable “skin” model to determine if the prodrugs and the investigational co-drugs derived from ALA and MPA are sufficiently metabolized to release therapeutically effective doses of the parent compounds that elevate protoporphyrin IX (PpIX) and inhibit inosine-5′-monophosphate dehydrogenase (IMPDH). HaCaT cells were grown, and cultures were treated with ALA-BE and ALA separately to evaluate the increase in PpIX which is hypothesized to correlate with hydrolysis of ALA-BE into the active compound ALA. MPA-ME was synthesized, HaCaT cell lysate was prepared, and the lysates were treated with MPA and MPA-ME. The MPA treated lysates were analyzed using HPLC to determine the extraction efficiency of MPA and the MPA-ME treated lysates were analyzed using HPLC to determine the percent hydrolysis of MPA-ME into the active compound MPA. This research establishes that HaCaT cells contain hydrolytic enzymes capable of promoting hydrolysis of ALA-/MPA- prodrugs and co-drugs that results in release of the parent drugs, ALA and MPA. The activity of the parent compounds correlates with the extent to which the prodrugs and co-drugs hydrolyze in epithelial cells.
dc.description.degreeMS in Pharmaceutical Sciences
dc.description.urihttps://acphs.on.worldcat.org/oclc/1416903625
dc.format.extent65 pages
dc.identifier.citationStrumski K. Assessment of hydrolysis of prodrugs and co-drugs derived from 5-aminolevulinic acid and mycophenolic acid [thesis]. Ann Arbor (MI): Proquest LLC; 2023. 65 p.
dc.identifier.thesis30488203
dc.identifier.urihttps://hdl.handle.net/20.500.14303/548
dc.language.isoen
dc.publisherProQuest LLC
dc.relation.ispartofAlbany College of Pharmacy and Health Sciences Theses
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dc.subjectAminolevulinic Acid
dc.subjectMycophenolic Acid
dc.subjectPsoriasis
dc.subjectProdrugs
dc.subjectHydrolysis
dc.titleAssessment of Hydrolysis of Prodrugs and Co-drugs Derived from 5-Aminolevulinic Acid and Mycophenolic Acid
dc.typeThesis
local.departmentprogramBS/MS Pharmaceutical Sciences
local.departmentprogramDepartment of Life Sciences
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Masters of Science in Pharmaceutical Sciences Theses
Hass, Martha Theses Advised