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: ex situ incorporation into wet BCMs, ex situ incorporation by swelling of dry BCMs, and an in situ 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.

Characterization of cubosomes immobilized in hydrogels of hyaluronic acid and their use for diclofenac controlled delivery.

Cubosomes are dispersions of bicontinuous surfactant phases that constitute an assertive option to carry and release drugs and biomolecules, offering high efficiency of entrapment and specificity towards biological targets. This paper reports, for the first time to the best of our knowledge, the immobilization and characterization of cubosomes in chemically cross-linked oxi-hyaluronic acid and the evaluation of their use for controlled delivery of diclofenac, which is chosen as a model drug. Immobilized cubosomes prepared with phytantriol and bearing either negative or positive charges (in this case due to the addition of a cationic surfactant) were characterized by small angle X-ray scattering (SAXS) analysis and high-resolution confocal microscopy, confirming that their internal structure remains unaltered and that they appear uniformly distributed within the hydrogel matrix. Their release properties were assessed, and a limited leaching of the cubosomes from the hydrogel matrix with sustained release of the entrapped diclofenac was confirmed. These results enable the use of immobilized cubosomes as an attractive platform for biomedical applications, significantly extending the already promising features of cubosomes.

Influence of the state of phase of lipid bilayer on the exposure of glucose residues on the surface of liposomes.

The presence of carbohydrate-binding proteins (i.e. lectins) on the surface of various bacterial strains and their overexpression in some tumor tissues makes the use of glycosylated liposomes a promising approach for the specific drug delivery in antibacterial and anti-cancer therapies. However, the functionalization of liposome surface with sugar moieties by glycosylated amphiphiles does not ensure the binding of sugar-coated vesicles with lectins. In fact, the composition and properties of lipid bilayer play a pivotal role in the exposure of sugar residues and in the interaction with lectins. The influence of the length of the hydrophilic spacer that links the sugar to liposome surface and of the presence of saturated or unsaturated phospholipids in the lipid bilayer on the ability of glucosylated liposomes to interact with a model lectin, Concanavalin A, was investigated. Our results demonstrate that both the chain length and the prensece of unsaturation, parameters that strongly affect the fluidity of the lipid bilayer, affect agglutination. In particular, agglutination is favored when liposomes are in the gel phase within a defined range of temperature. Moreover, the obtained results confirm that the length of the PEG spacer, that influences both lipid organization and the exposure of sugar moieties to the bulk, plays a crucial role in liposome/lectin interaction.