A Stepwise Framework for the Systematic Development of Lipid Nanoparticles

Abstract

A properly designed nanosystem aims to deliver an optimized concentration of the active pharmaceutical ingredient (API) at the site of action, resulting in a therapeutic response with reduced adverse effects. Due to the vast availability of lipids and surfactants, producing stable lipid dispersions is a double-edged sword: on the one hand, the versatility of composition allows for a refined design and tuning of properties; on the other hand, the complexity of the materials and their physical interactions often result in laborious and time-consuming pre-formulation studies. However, how can they be tailored, and which premises are required for a “right at first time” development? Here, a stepwise framework encompassing the sequential stages of nanoparticle production for disulfiram delivery is presented. Drug in lipid solubility analysis leads to the selection of the most suitable liquid lipids. As for the solid lipid, drug partitioning studies point out the lipids with increased capacity for solubilizing and entrapping disulfiram. The microscopical evaluation of the physical compatibility between liquid and solid lipids further indicates the most promising core compositions. The impact of the outer surfactant layer on the colloidal properties of the nanosystems is evaluated recurring to machine learning algorithms, in particular, hierarchical clustering, principal component analysis, and partial least squares regression. Overall, this work represents a comprehensive systematic approach to nanoparticle formulation studies that serves as a basis for selecting the most suitable excipients that comprise solid lipid nanoparticles and nanostructured lipid carriers.

Nanostructured Lipid Carriers Enriched Hydrogels for Skin Topical Administration of Quercetin and Omega-3 Fatty Acid

“…Given the vast array of lipids available to produce NLCs, the most promising core compositions were selected by the microscopical and macroscopical assessment of the physical compatibility between liquid and solid lipids, which was performed in a similar way to the lipid compatibility and miscibility procedures described by Basso et al [ 28 ]. Q solubilization within the most promising lipids or lipid mixture at different wt% was also microscopically and macroscopically evaluated.…”

Solid Lipid Nanoparticles: Review of the Current Research on Encapsulation and Delivery Systems for Active and Antioxidant Compounds

“…Surfactants act as a barrier between the lipid matrix on the outside of the particles. Solid lipids that can be used are saturated fats in the form of free fatty acids, mono- and diglycerides, triglycerides, and other fatty acid esters that act as binders of active substances or drugs in the lipid matrix [ 43 , 44 , 45 ].…”

Assessing the Synergistic Activity of Clarithromycin and Therapeutic Oils Encapsulated in Sodium Alginate Based Floating Microbeads

“…Many studies have reported variation in the entrapment efficiency of active ingredients in carriers using various lipids or oils. This is because drugs demonstrate a variable solubility in these lipids and oils [37,38].…”