Anti-proliferative effect of Aminolevulinic acid (ALA) and Mycophenolic acid (MPA) with blue light irradiation
Loading...
Issue Date
2021-12
Authors
Capriglione, Noelle Grace '21
Degree
MS in Pharmaceutical Sciences
Advisor
Voigt, Jeffrey M
Hass, Martha A
Hass, Martha A
Committee Members
Dearborn, Richard E.
Journal Title
Journal ISSN
Volume Title
Abstract
Combining the photodynamic therapeutic (PDT) effects of aminolaevulinic acid (ALA) coherently with the chemotherapeutic benefits of mycophenolic acid (MPA) for psoriasis treatment, as a codrug has never been pursued. ALA is an endogenous molecule currently used in PDT for psoriasis by limiting the hyperproliferation of keratinocytes which characterizes psoriasis and manifests as scaling layered plaques on the skin. The application of ALA increases the production of photosensitizer protoporphyrin IX-(PpIX) through a PpIX mediated mechanism that reduces cell viability when irradiated. MPA, another reliable treatment for psoriasis, inhibits the function of an enzyme essential for purine synthesis called inosine monophosphate dehydrogenase (IMPDH) which is specific for resident and infiltrating T-cells in psoriatic skin. The goal of this research is to investigate how MPA affects the ability of ALA to induce an elevation of PpIX levels in keratinocytes and subsequently how MPA affects cell viability of ALA-treated HaCaT cells exposed to blue light. In vitro activity of ALA and the effect of MPA on this activity were established by measuring PpIX concentration in HaCaT cells treated with various doses of ALA alone or in combination with MPA, using fluorescence spectroscopy. Cytotoxicity of drug treatments with and without blue-light irradiation was determined using a cell viability assay. PpIX formation in ALA-treated HaCaT cells increased in a dose-response manner as concentration treatments of ALA (in PBS) increased (250, 500, 1000\302\265M). MPA did not significantly hinder ALA functionality for PpIX generation in HaCaT cells when treated in (1:1) combination at 500 and 1000\302\265M. We observed significant cytotoxic effects in HaCaT cells treated with ALA at 500 and 1000\302\265M, after blue-light exposure. This cytotoxicity was observed to the same extent in HaCaT cells treated in an equimolar combination treatment with MPA, at 500\302\265M. The cytotoxicity observed from the phototherapy with ALA treatment alone was enhanced at 1000\302\265M in the (1:1) combination treatment, ALA + MPA. More experiments will need to be done with a wider range of concentration treatments at dosages of ALA where PpIX formation is detectable in HaCaT cells. The combination of ALA + MPA seems to be a suitable co-drug candidate. The possible effects of ALA on MPA functionality, in IMDPH inhibition, must be explored.
Citation
Capriglione, NG. Anti-proliferative effect of aminolevulinic acid (ALA) and mycophenolic acid (MPA) with blue Light irradiation.\357\277\275Ann Arbor (MI): Proquest LLC; 2021. 114 p.
ACPHS Research Commons URI
Description
Click on the Resource Link to find this item in the ACPHS Library catalog.