Monoolein Cubic Phase Gels and Cubosomes Doped with Magnetic Nanoparticles-Hybrid Materials for Controlled Drug Release.

Hybrid materials consisting of a monoolein lipidic cubic phase (LCP) incorporating two types of magnetic nanoparticles (NP) were designed as addressable drug delivery systems. The materials, prepared in the form of a gel, were subsequently used as a macroscopic layer modifying an electrode and, after dispersion to nanoscale, as magnetocubosomes. These two LCPs were characterized by small-angle X-ray scattering (SAXS), cross-polarized microscopy, magnetic measurements, and phase diagrams. The magnetic dopants were hydrophobic NPoleic and hydrophilic NPcitric, characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and their influence on the properties of the cubic phases was investigated. The removal of the anticancer drug, Doxorubicin (Dox) from the hybrid cubic phase gels was studied by electrochemical methods. The advantages of incorporating magnetic nanoparticles into the self-assembled lipid liquid crystalline phases include the ability to address the cubic phase nanoparticle containing large amounts of drug and to control the kinetics of the drug release.

Design and assembly of pH-sensitive lipidic cubic phase matrices for drug release.

Bicontinuous lipidic cubic phases (LCPs) exhibit a combination of material properties that make them highly interesting for various biomaterial applications: they are nontoxic, biodegradable, optically transparent, thermodynamically stable in excess water, and can incorporate active molecules of virtually any polarity. Here we present a molecular system comprising host lipid, water, and designed lipidic additive, which form a structured, pH-sensitive lipidic matrix for hydrophilic as well as hydrophobic drug incorporation and release. The model drug doxorubicin (Dox) was loaded into the LCP. Tunable interactions with the lipidic matrix led to the observed pH-dependent drug release from the phase. The rate of Dox release from the cubic phase at pH 7.4 was low but increased significantly at more acidic pH. A small amount of a tailored diacidic lipid (lipid 1) added to the monoolein LCP modified the release rate of the drug. Phase identity and structural parameters of pure and doped mesophases were characterized by small-angle X-ray scattering (SAXS), and release profiles from the matrix were monitored electrochemically. Analysis of the release kinetics revealed that the total amount of drug released from the LCP matrix is linearly dependent on the square root of time, implying that the release mechanism proceeds according to the Higuchi model.