Antifungal invertebrate bioencapsulation: a potential solution to poor patient compliance

Fungi within the order Onygenales, including the genera Nannizziopsis, Paranannizziopsis, Ophidiomyces, and the newly described Emydomyces lead to morbidity and mortality of reptiles in companion and managed care settings. Emydomyces testavorans (ET) is a fungal disease associated with significant morbidity and mortality in chelonians. Nannizziopsis guarroi (NG) is a cutaneous mycosis that causes severe morbidity, and often mortality in companion reptile species and has been widely diagnosed in the United States. Despite the prevalence of these infections in chelonians and companion reptiles, a major hurdle in effective treatment of mycoses is the prolonged treatment course and compliance of orally administered antifungal medications. Bioencapsulation is a method of drug administration, whereby a drug is accumulated into a biological substrate. In the case of carnivorous and/or insectivorous species, bioencapsulation into a prey item for consumption by the target species presents a unique strategy for pharmacotherapeutic delivery. This project describes the formulation of bioencapsulated invertebrates though diet and intracoelomic injection. We then tested the application of this bioencapsulation technique by evaluating the pharmacokinetics of terbinafine, given orally by gavage or through the ingestion of a bioencapsulated earthworm, in ET infected western pond turtles (Actinemys marmorata). Terbinafine was successfully incorporated into five different gelatin diets for invertebrate feeding trials using three commonly used feeder insects [king worms (Zophobas morio), crickets (Acheta domesticus) and Dubia roaches (Blaptica dubia)]. Feeding trials utilizing a medical grade gelatin with and without terbinafine added had overall poor palatability overall and high mortality in crickets and king worms. By incorporating terbinafine into commercial insect and turtle gelatin diets, palatability and overall was mildly improved. Quantitative assessment of diet consumption and bioencapsulation within the invertebrate source was unable to be performed. The method of intracoelomic injection of terbinafine into an earthworm (Lumbricus terrestris) was demonstrated as a successful method of bioencapsulation. Compounded terbinafine (25 mg/mL; 30 mg/kg) was administered through oral gavage (OG) directly into the stomach or bioencapsulated (BEC) into an earthworm vehicle and administered to seven ET infected A. marmorata. There was a significant (p=0.031) increase in area under the curve with BEC compared to OG. Using steady state predictions, with once daily terbinafine administration, 3/7 and 7/7 turtles had plasma concentrations persistently greater than the minimum inhibitory concentration (MIC) for ET, for the OG and BEC routes of administration, respectively. With dosing every 48 hours, 3/7 turtles for OG administration and 6/7 turtles for BEC administration had concentrations greater than the ET MIC throughout the entire dosing interval. This method of bioencapsulation has the potential to improve patient compliance for medication administration in insectivores. The methodologies in diet formation and administration will be used to assess the application of bioencapsulation for additional antimicrobials and in future studies assessing efficacy in clinical cases.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

VMS-Veterinary Clinical Medcne

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Cerreta, Anthony J.

Contributors dc:contributor

• Keller, Krista A
• O’Connor, Matthew R
• Forsythe, Lauren R
• Reinhart, Jennifer M

• Emydomyces Testavorans
• Western Pond Turtle
• Actinemys Marmorata
• Bioencapsulation
• Invertebrate

Statement dc:rights

• Copyright 2022 Anthony Cerreta

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/117582

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F117582