Rectally Administered Budesonide-Loaded Phase Transformable Premix Offers Improved Recovery of Intestinal Mucosa in...

The present study investigates the water-induced formation of liquid crystalline (LC) structures from a premix. The latter consisted of oleic acid (oil phase), d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS; surfactant), and Transcutol P (cosurfactant). Pseudoternary phase diagrams were constructed at three ratios of the surfactant-cosurfactant mixture (S_mix) and investigated for phase transition. The compositions with 3:1 S_mix ratio were comprehensively characterized along a water dilution line. Polarized light microscopy revealed the onset of birefringence with increasing water content, indicative of the evolution of LC structures. This was further verified by the shifts in scattering peaks and the emergence of higher-order Bragg peaks in SAXS experiments. The observed structures were denoted as nonlamellar liquid crystals. Amplitude and frequency sweep tests showed that the as-formed phases were viscoelastic and exhibited structural resilience under shear. Ex vivo bioadhesion experiments showed a prolonged residence of the LC formulation in the chicken ileum. The formulation was loaded with budesonide (BDS), and its efficacy was studied in a male C57BL/6 mouse model of ulcerative colitis (UC). Subsequent to rectal administration, therapeutic outcomes were compared in terms of biochemical and histopathological data. Western blotting was performed to evaluate the expression of colonic epithelial tight junction proteins (occludin and ZO-1). We found that the rectally administered formulation can alleviate the symptoms and pathological signatures of UC. The formulation exerted its effects by suppressing the oxidative stress-inflammation axis and restoring the integrity of the colonic barrier.