Linoleic acid-based pH-sensitive 5-ASA nanocubosome pellets for colon targeting in ulcerative colitis: in vitro and in vivo comparison with non-pH-sensitive and conventional formulations.

OBJECTIVE

This study aimed to design and evaluate pH-sensitive pellets loaded with 5-aminosalicylic acid (5-ASA) for targeted colon delivery in ulcerative colitis (UC) therapy.

SIGNIFICANCE: The proposed formulation leverages glyceryl monooleate (GMO) and linoleic acid (LA) as liquid crystal precursors to achieve site-specific drug release.

METHODS

Liquid crystal nanoparticles (LCNPs) were prepared from a GMO bulk phase using a top-down method, with LA added for pH sensitivity. The formulations were then evaluated for drug loading, encapsulation efficiency, and structure by polarized light microscopy, with drug release tested at pH 1.2 and 6.8. The LCNPs dispersions were then used to make pellets using the extrusion-spheronisation technique. Drug-excipient interactions were examined by FTIR and DSC. The pellet formulations were finally tested in a rat ulcerative colitis (UC) model by comparing colon damage scores across treatment groups.

RESULTS

The pH-sensitive pellets containing LCNPs exhibited a uniform morphology, desirable aspect ratio, and sufficient mechanical strength. The in vitro release profile demonstrated a 5.7-fold higher drug release at pH 6.8 compared to pH 1.2. This targeted release was ascribed to a pH-triggered phase transition of the LA and electrostatic repulsion between the ionized drug and the carrier. The in vivo results confirmed that the pH-sensitive pellets elicited the most pronounced and statistically significant (p < 0.05) reduction in colon damage scores.

CONCLUSION

The developed pellet system, which encapsulates 5-ASA within GMO/LA-based liquid crystal nanoparticles, presents a highly promising platform for targeted drug delivery in the treatment of ulcerative colitis.