No abstract

The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

Self‐assembly of lipid‐based liquid crystalline (LLC) nanoparticles is a formulation art arising from the hydrophilic–lipophilic qualities and the geometric packing of amphiphilic lipid molecules in an aqueous environment. The diversity of commercialized amphiphilic lipids and an increased understanding of the physicochemical factors dictating their membrane curvature has enabled versatile architectural design and engineering of LLC nanoparticles. While these exotic nanostructured materials are hypothesized to form the next generation of smart therapeutics for a broad field of biomedical applications, biological knowledge particularly on the systemic biocompatibility or cytotoxicity of LLC materials remains unclear. Here, an overview on the interactions between LLCs of different internal nanostructures and biological components (including soluble plasma constituents, blood cells, and isolated tissue cell lines) is provided. Factors affecting cell–nanoparticle tolerability such as the type of lipids, type of steric stabilizers, nanoparticle surface charges, and internal nanostructures (or lipid phase behaviors) are elucidated. The mechanisms of cellular uptake and lipid transfer between neighboring membrane domains are also reviewed. A critical analysis of these studies sheds light on future strategies to transform LLC materials into a viable therapeutic entity ideal for internal applications.

The rate and extent of lipolysis, the breakdown of fat into molecules that can be absorbed into the bloodstream, depend on the interfacial composition and structure of lipid (fat) particles. A novel method for controlling the interfacial properties is to load the lipid into porous colloidal particles. We report on the role of pore nanostructure and surface coverage in controlling the digestion kinetics of medium-chain and long-chain triglycerides loaded into porous silica powders of different particle size, porosity, and hydrophobicity/hydrophilicity. An in vitro lipolysis model was used to measure digestion kinetics of lipid by pancreatic lipase, a digestive enzyme. The rate and extent of lipid digestion were significantly enhanced when a partial monolayer of lipid was loaded in porous hydrophilic silica particles compared to a submicrometer lipid-in-water emulsion or a coarse emulsion. The inhibitory effect of digestion products was clearly evident for digestion from a submicrometer emulsion and coarse emulsion. This effect was minimal, however, in the two silica-lipid systems. Lipase action was inhibited for lipid loaded in the hydrophobic silica and considered due to the orientation of lipase adsorption on the methylated silica surface. Thus, hydrophilic silica promotes enhanced digestion kinetics, whereas hydrophobic silica exerts an inhibitory effect on hydrolysis. Evaluation of digestion kinetics enabled the mechanism for enhanced rate of lipolysis in silica-lipid systems to be derived and detailed. These investigations provide valuable insights for the optimization of smart food microparticles and lipid-based drug delivery systems based on lipid excipients and porous nanoparticles.

We investigate the role of hydrophilic fumed silica in controlling the digestion kinetics of lipid emulsions, hence further exploring the mechanisms behind the improved oral absorption of poorly soluble drugs promoted by silica-lipid hybrid (SLH) microcapsules. An in vitro lipolysis model was used to quantify the lipase-mediated digestion kinetics of a series of lipid vehicles formulated with caprylic/capric triglycerides: lipid solution, submicrometer lipid emulsions (in the presence and absence of silica), and SLH microcapsules. The importance of emulsification on lipid digestibility is evidenced by the significantly higher initial digestion rate constants for SLH microcapsules and lipid emulsions (>15-fold) in comparison with that of the lipid solution. Silica particles exerted an inhibitory effect on the digestion of submicrometer lipid emulsions regardless of their initial location, i.e., aqueous or lipid phases. This inhibitory effect, however, was not observed for SLH microcapsules. This highlights the importance of the matrix structure and porosity of the hybrid microcapsule system in enhancing lipid digestibility as compared to submicrometer lipid emulsions stabilized by silica. For each studied formulation, the digestion kinetics is well correlated to the corresponding in vivo plasma concentrations of a model drug, celecoxib, via multiple-point correlations (R(2) > 0.97). This supports the use of the lipid digestion model for predicting the in vivo outcome of an orally dosed lipid formulation. SLH microcapsules offer the potential to enhance the oral absorption of poorly soluble drugs via increased lipid digestibility in conjunction with improved drug dissolution/dispersion.