title: A novel approach for long-term oral drug administration in animal research.
abstract: In the field of pharmacological research, the oral consumption of anastrozole, an aromatase inhibitor, when added to an animal's drinking water is hindered by poor drug palatability and environmental loss of drug solution. To overcome these caveats, we developed a novel approach for the oral delivery of anastrozole mixed in a solid hydration gel matrix that functions as a replacement for water. Heated hydration gel was mixed with anastrozole and distributed into a gel delivery device consisting of a 50 mL plastic conical tube containing four stacked 200 μL pipette tips to allow for air pressure induced gel disbursement. Transgenic female 3xTgAD mice were randomized to receive either anastrozole-treated or untreated hydration gel at 3 months of age. Body weights were recorded weekly, and gel consumption was measured every 1-3 days. Six months post treatment mice were killed and serum anastrozole levels were determined using liquid chromatography-mass spectrometry (LC-MS). Anastrozole-treated mice gained significantly more weight despite consuming significantly less hydration gel compared to vehicle treated mice. LC-MS analysis, using a low serum volume (10 μL), revealed average anastrozole serum levels of 2.91 ng/mL. Anastrozole-treated ovarian tissue displayed ovarian cysts, massive edema-like stroma, and also lacked corp lutea compared to control mice. These findings demonstrate that hydration gel delivered using the newly developed oral delivery method is a viable approach for pharmacological research involving compounds with poor palatability, low water solubility, and cost prohibitive compounds where environmental loss needs to be minimized.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Cassia R
authors.initials: CR
authors.lastname: Overk
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Borgia
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000077384:Anastrozole; D032761:Animal Experimentation; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002853:Chromatography, Liquid / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D005782:Gels; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D009570:Nitriles / Q000008:administration & dosage / Q000097:blood; D053764:Presenilin-1 / Q000235:genetics; D015203:Reproducibility of Results; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood; D016875:tau Proteins / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D014150:Antipsychotic Agents; D005782:Gels; D009570:Nitriles; C508853:PSEN1 protein, human; D053764:Presenilin-1; D014230:Triazoles; D016875:tau Proteins; D000077384:Anastrozole