Cubosome-carrying bacterial cellulose membrane as a versatile drug delivery platform

Using advanced nanotechnology membranes has opened up new possibilities in the field of biomedicine, particularly for controlled drug delivery and especially for topical use. Bacterial cellulose membranes (BCM), particularly, have gained prominence owing to their distinctive attributes, including remarkable water retention, safety, biodegradability, and tunable gas exchange. However, they are aqueous matrices and, for this reason, of limited capacity for incorporation of apolar compounds. Cubosomes are lipid nanoparticles composed of a surfactant bicontinuous reverse cubic phase, which, owing to their bicontinuous structure, can incorporate both polar and apolar compounds. Therefore, these particles present a promising avenue for encapsulating and releasing drugs and biomolecules due to their superior entrapment efficiency. In this study, we aim to extend earlier investigations using polymeric hydrogels for cubosome immobilization, now using BCMs, a more resilient biocompatible matrix. Phytantriol cubosome-loaded BCMs were prepared by three distinct protocols: incorporation into wet BCMs, incorporation by swelling of dry BCMs, and an process with the growth of BCMs in a sterile medium already containing cubosomes. Our investigation revealed that these methodologies ensured that cubosomes remained integral, uniformly distributed, and thoroughly dispersed within the membrane, as confirmed using Small-Angle X-ray Scattering (SAXS) and high-resolution confocal microscopy. The effective incorporation and sustained release of diclofenac were validated across the different BCMs and compared with hyaluronic acid (HA) hydrogel in our previous studies. Furthermore, the resistance against cubosome leaching from the three BCM and HA hydrogel samples was quantitatively evaluated and contrasted. We hope that the outcomes from this research will pave the way for innovative use of this platform in the incorporation and controlled release of varied active agents, amplifying the already multifaceted applicability of BCMs.