A new supra-organized hybrid material obtained in aqueous medium via anionic exchange of self-assembled unilamellar anionic liposomes with the nitrate ions present in the interlayers of layered double hydroxides (LDH) is fully characterized. This material presents original properties linked to the simultaneous presence of a phospholipid bilayer derived from liposomes, still used as vectors for lipophilic drugs, and LDH, which protects the bilayer and brings about a pH sensitivity. The exchange rate is controlled via the added amount of liposomes. TGA, XRD, and TEM confirm the organization of the entrapped phospholipids as a bilayer. The presence of the latter allows the material to load lipophilic and neutral drugs, which represent the largest fraction of those newly synthesized. Furthermore, in physiological conditions, preliminary tests show a sustained release of phospholipids (1.5% for 7 days and 6% for 14 days), whereas a fluorescent lipophilic drug-mimic reveals the reorganization of the phospholipids into liposomes in the release medium. In the field of biocompatible materials, these new hybrid particles have a strong potential for the storage and sustained release of neutral or lipophilic drugs.

Abstract:In this study, we describe the elaboration of multifunctional positively charged polyelectrolyte complex (PEC) nanoparticles, designed to be stable at physiological salt concentration and pH, for effective targeted delivery. These nanoparticles were obtained by charge neutralization between chitosan (CS) as polycation and hyaluronic acid (HA) as polyanion. We showed that the course of the complexation process and the physico-chemical properties of the resulting colloids were impacted by (i) internal parameters such as the Degree of Acetylation (DA, i.e., the molar ration of acetyl glucosamine residues) and molar mass of CS, the HA molar mass and (ii) external parameters like the charge mixing ratio and the polymer concentrations. As a result, nonstoichiometric colloidal PECs were obtained in water or PBS (pH 7.4) and remained stable over one month. The polymer interactions were characterized by thermal analysis (DSC and TGA) and the morphology was studied by scanning electron microscopy. A model antibody, anti-ovalbumine (OVA) immunoglobulin A (IgA) was sorbed on the particle surface in water and PBS quantitatively in 4 h. The CS-HA/IgA nanoparticles average size was between 425-665 nm with a positive zeta potential. These results pointed out that CS-HA can be effective carriers for use in targeted drug delivery.

A novel bio-hybrid drug delivery system was obtained involving a Mg/Al-NO3 layered double hydroxide (LDH) intercalated either with ibuprofenate anions (IBU) or a phospholipid bilayer (BL) containing a neutral drug, i.e., 17β-estradiol, and then embedded in chitosan beads. The combination of these components in a hierarchical structure led to synergistic effects investigated through characterization of the intermediates and the final bio-composites by XRD, TG, SEM, and TEM. That allowed determining the presence and yield of IBU and of BL in the interlayer space of LDH, and of the encapsulated LDH in the beads, as well as the morphology of the latter. Peculiar attention has been paid to the intercalation process of the BL for which all available data substantiate the hypothesis of a first interaction at the defect of the LDH, as well as on the interaction mode of these components. 1H, 31P and 27Al MAS-NMR studies allowed establishing that the intercalated BL is not homogeneous and likely formed patches. Release kinetics were performed for sodium ibuprofenate as well as for the association of 17β-estradiol within the negatively charged BL, each encapsulated in the LDH/chitosan hybrid materials. Such new bio-hybrids offer an interesting outlook into the pharmaceutical domain with the ability to be used as sustained release systems for a wide variety of anionic and, importantly, neutral drugs.