Recent Advances in the Development of Liquid Crystalline Nanoparticles as Drug Delivery Systems

Abstract

Due to their distinctive structural features, lyotropic nonlamellar liquid crystalline nanoparticles (LCNPs), such as cubosomes and hexosomes, are considered effective drug delivery systems. Cubosomes have a lipid bilayer that makes a membrane lattice with two water channels that are intertwined. Hexosomes are inverse hexagonal phases made of an infinite number of hexagonal lattices that are tightly connected with water channels. These nanostructures are often stabilized by surfactants. The structure's membrane has a much larger surface area than that of other lipid nanoparticles, which makes it possible to load therapeutic molecules. In addition, the composition of mesophases can be modified by pore diameters, thus influencing drug release. Much research has been conducted in recent years to improve their preparation and characterization, as well as to control drug release and improve the efficacy of loaded bioactive chemicals. This article reviews current advances in LCNP technology that permit their application, as well as design ideas for revolutionary biomedical applications. Furthermore, we have provided a summary of the application of LCNPs based on the administration routes, including the pharmacokinetic modulation property.

Keywords: cubosomes; drug delivery systems; hexosomes; liquid crystalline nanoparticles (LCNPs); theranostics; vaccine delivery.

Figure 4

Representative PLM textures, cryo-TEM images, and SAXS patterns of lipid nanoparticles for cubosomes and hexosomes. PLM: polarized light microscopy; cryo-TEM: cryo-transmission electron microscopy; SAXS: small-angle X-ray scattering. Adapted with permission from [66,67].

Figure 1

A summary of the common lipids and preparation methods used to make liquid crystalline nanoparticles (LCNPs), as well as their possible characterization techniques and therapeutic potentials.

Figure 2

Schematic of self-assembly structures of commonly observed lyotropic liquid crystalline phases corresponding to critical packing parameter (CPP) values. This parameter is given as $\mathrm{C}\mathrm{P}\mathrm{P}=v/a_0{l}_c$ where $v$ is the hydrophobic chain volume, $a_0$ is the effective headgroup area, and $l_c$ is the effective hydrophobic chain length. For $\mathrm{C}\mathrm{P}\mathrm{P}\approx 1$, lamellar L_α phase is observed with zero mean curvature. In order of increasing negative curvature $(\mathrm{C}\mathrm{P}\mathrm{P}>1)$, these are sponge L₃, inverse bicontinuous cubic Im3m, Pn3m, Ia3d, hexagonal H_II, inverse discontinuous micellar cubic Fd3m, and inverse micelles L₂. Reproduced in part from [W.F.N. Wan Iskandar et al., Colloids and Surfaces A: Physicochemical and Engineering Aspects 623 (2021) 126697] [50] with permission from Elsevier.

Figure 3

Schematic illustration of various preparation methods.