Increased Absorption of Thyroxine in a Murine Model of Hypothyroidism Using Water/CO₂ Nanobubbles

Thyroxine (T4) is a drug extensively utilized for the treatment of hypothyroidism. However, the oral absorption of T4 presents certain limitations. This research investigates the efficacy of CO₂ nanobubbles in water as a potential oral carrier for T4 administration to C57BL/6 hypothyroid mice. Following 18 h of fasting, the formulation was administered to the mice, demonstrating that the combination of CO₂ nanobubbles and T4 enhanced the drug's absorption in blood serum by approximately 40%. To comprehend this observation at a molecular level, we explored the interaction mechanism through which T4 engages with the CO₂ nanobubbles, employing molecular simulations, semi-empirical quantum mechanics, and PMF calculations. Our simulations revealed a high affinity of T4 for the water-gas interface, driven by additive interactions between the hydrophobic region of T4 and the gas phase and electrostatic interactions of the polar groups of T4 with water at the water-gas interface. Concurrently, we observed that at the water-gas interface, the cluster of T4 formed in the water region disassembles, contributing to the drug's bioavailability. Furthermore, we examined how the gas within the nanobubbles aids in facilitating the drug's translocation through cell membranes. This research contributes to a deeper understanding of the role of CO₂ nanobubbles in drug absorption and subsequent release into the bloodstream. The findings suggest that utilizing CO₂ nanobubbles could enhance T4 bioavailability and cell permeability, leading to more efficient transport into cells. Additional research opens the possibility of employing lower concentrations of this class of drugs, thereby potentially reducing the associated side effects due to poor absorption.