The Toxicological Effects of Duloxetine as a Polymeric Nanoparticle Drug Delivery System in Rats
Sciences and Mathematics, College of
Psychological Science, Department of
BURS Faculty Advisor
Dr. Jordyn Wilcox
Duloxetine (Cymbalta), a serotonin-norepinephrine reuptake inhibitor (SNRI) is an antidepressant which has previously shown relatively low negative toxicological effects and promising depressive symptom management. However, Duloxetine (DLX) encounters an issue in its drug delivery performance due to its high metabolic dissolution rate which can influence both potency and efficacy. Nanoparticles, in particular, Solid Lipid Nanoparticles (SLNs) can be used as an effective drug carrier system for DLX. If DLX is paired with a SLN (SLN-DLX) for depression treatment, it could provide a relatively low toxicity effect while increasing the concentration of the drug’s potency in particular to the brainstem and 5-HT terminal areas. While using nano-template engineering techniques, SLN-DLX solutions were fabricated to be further analyzed for toxicological analysis in a rodent model. Equal numbers of 3-month-old male and female Long-Evans Rats received daily 10 mL/kg intraperitoneal (IP) injections of either 5 mg/kg DLX, 5 mg/kg SLN-DLX, SLN, or saline vehicle on four consecutive days. General physical appearance and daily weights were recorded during treatment. Rats were euthanized and brains collected and post-fixed in paraformaldehyde on the fifth experimental day for further histological analysis. We hypothesized that rats with SLN injections and SLN-DLX injections will exhibit no toxicological differences when compared to the saline group. There was no significant effect on weight in any treatment group, p > .05. Histological analyses are forthcoming, but we hypothesize that there will be no significant toxicological difference between treatment groups. For future directions, we hope to conduct a study looking into behavioral differences in chronic stress induced rodent models from the same administration of treatments.
Walters, Teel; Nabi, Husna; Wilcox, Dr. Jordyn; and Ferrara, Dr. Davon, "The Toxicological Effects of Duloxetine as a Polymeric Nanoparticle Drug Delivery System in Rats" (2023). Belmont University Research Symposium (BURS). 239.