Microencapsulation of an amphotericin B-solubilising mucolytic deep eutectic solvent for enhanced oral delivery to treat cystic fibrosis.

This study aimed to develop an innovative oral formulation of Amphotericin B (AmB) for the treatment of intestinal symptoms related to cystic fibrosis (CF) using microcapsules produced via the prilling/vibration technique. The use of a mucolytic Deep Eutectic Solvent (DESolve) aimed to improve the solubility of AmB and its diffusion through the mucus barrier by reducing its viscosity. Diffusion tests in purified intestinal mucus and mucin confirmed the ability to penetrate the thick mucus barrier typical of CF, enhancing drug availability at the target site. In vitro distribution studies on Caco-2/HT29 MTX E-12 cells showed that DESolve markedly increased the amount of cell-associated AmB compared with H2OAmB, indicating greater drug association with the epithelial compartment, which may facilitate AmB access to the cell membrane, where it could potentially exert its ion-channel-forming activity. To enable oral administration and protect the drug from gastric degradation, AmB solubilised in DESolve (DESAmB) was microencapsulated as a core using the prilling/vibration technique. An outer polymer shell that protects AmB from gastric degradation and ensures targeted release in the small intestine was chosen. The microcapsules were successfully produced, achieving a high yield (90.49%) and encapsulation efficiency (96.04%). Dimensional analysis and scanning electron microscopy confirmed a uniform size distribution, spherical shape, smooth surface, free of cracks and pores. Swelling studies and drug release tests in simulated gastrointestinal fluid demonstrated the formulation's ability to release AmB in the intestinal environment. These results highlight the potential of the dual strategy, i.e. the use of a mucolytic DESolve and microcapsules with targeted release in the intestine, as an innovative, stable and effective strategy for the oral administration of AmB, offering a more accessible alternative for CF patients and improving treatment adherence.