Date of Graduation

8-2019

Document Type

Thesis

Degree Name

Bachelor of Science in Agricultural, Food and Life Sciences

Degree Level

Undergraduate

Department

Animal Science

Advisor/Mentor

Rosenkrans, Charles

Abstract

“Between January 1998 and March 2000, veterinarians at the ASPCA National Animal Poison Control Center (NAPCC) consulted on more than 1,050 cases of accidental exposures to acetaminophen and 1,100 cases of ibuprofen ingestion in dogs and cats” (Richardson, 2000).

NSAID toxicity has become an increasingly common occurrence in small companion animals within the last decade due to widespread usage (Zhou, Boudreau, & Freedman, 2014). Depending on the specific drug, treatment is centered around early decontamination and prevention of kidney and hepatic damage, and methemoglobanemia. Currently, methemoglobanemia is treated with intravenous delivery of methylene blue and less commonly through oral administration. While these methods have been shown to be successful, congenital forms of methemoglobinemia are more difficult to manage as reoccurring treatments are imperative.

A biocompatible hydrogel composed of Pluronic F127 and methylene blue was created at various percent weight ratios to analyze release kinetics and determine the most effective composition for clinical treatment of methemoglobinemia. Using a hydrogel for localized delivery of methylene blue allows for long-term release of the drug, making treatment more feasible for affected patients and their owners.

Initially, samples were created using 15-20 percent weight Pluronic F127 and deionized water in 20 mL vials. The polymer was allowed to dissolve by mechanical stirring using a magnetic stir bar for 24 hours. Once completely dissolved, 7.8%, 15.6%, or 31.2% methylene blue was added to each vial. Samples were placed in an oven at 37 degrees Celsius. Samples were observed on 60-second intervals to check for gel formation. At this critical point, the solution was no longer viscous. Clinically favorable samples achieved a gel formation time at less than 10 minutes while other concentrations remained liquefied after the 24-hour period.

A cumulative study was conducted with samples that did form a gel consistency to analyze the release kinetics of methylene blue. At day 0, 1 mL of phosphate buffered saline was added to each vial. Each day of the study, 1 mL of this phosphate buffered saline and methylene blue solution was removed and absorbance and concentration was measured using ultraviolet-visible spectroscopy. This mixture was then be discarded and new phosphate buffered saline was added to each sample until the gel had completely degraded. Samples of Pluronic F127 at 19 percent weight and above with 7.8% methylene blue proved to have the greatest longevity.

A second trial was conducted using 19-21 percent weight Pluronic F127 with 7.8% methylene blue in 10 mL and 20 mL vials to compare the effects of surface degradation. In comparison to the 20 mL vial, the 10 mL vial showed significant increase in longevity. Increased concentrations of Pluronic F127.

Of the samples analyzed, 21 percent weight Pluronic F127 and 7.8% methylene blue proved to be the most clinically favorable sample for long-term delivery. Gel formation occurred instantly at room temperature and degraded over a period of 7 days. This specific sample also showed to have the highest percentage of methylene blue released during the cumulative release study.

Keywords

methemoglobinemia, hydrogels

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