A novel approach for long-term oral drug administration in animal research

• Published in: Journal of neuroscience methods 2011-02, Vol.195 (2), p.194-199
• Main Authors: Overk, Cassia R., Borgia, Jeffrey A., Mufson, Elliott J.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Alzheimer Disease - drug therapy; Amyloid beta-Protein Precursor - genetics; Anastrozole; Animal Experimentation; Animals; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - blood; Body Weight - drug effects; Chromatography, Liquid - methods; Disease Models, Animal; Female; Gels; Humans; Hydration gel; Liquid chromatography–mass spectrometry; Mass Spectrometry; Mice; Mice, Transgenic; Nitriles - administration & dosage; Nitriles - blood; Oral administration; Ovary; Pharmacology; Presenilin-1 - genetics; Reproducibility of Results; tau Proteins - genetics; Triazoles - administration & dosage; Triazoles - blood
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2010.12.009

▶ Hydration gel combined with a gel delivery device is a viable method for the oral delivery of anastrozole. ▶ Anastrozole levels were quantified from 10μL of serum using LC–MS. ▶ Anastrozole caused weight gain and changes in ovarian structure indicating that the dosing was biologically active. 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 50mL plastic conical tube containing four stacked 200μL 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 (10μL), revealed average anastrozole serum levels of 2.91ng/mL. Anastrozole-treated ovarian tissue displayed ovarian cysts, massive edema-like stroma, and also lacked corpa 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.