Are lipid nanoparticles really superior? A holistic proof of concept study

Lipid nanoparticles are a successful carrier system for dermal drug delivery. They possess various beneficial properties, i.e., increased chemical stability for chemically labile compounds, increased dermal penetration of active compounds, or skin carrying properties after dermal application due to the formation of a so-called “invisible patch.” Despite manifold studies showing these properties individually, a study that investigates if one lipid nanoparticle formulation can really combine all the above-mentioned benefits at once is not yet available. In the present study, lipid nanoparticles (NLC) were produced and characterized regarding their physico-chemical properties. The chemical stability of the incorporated active ingredient (AI) was determined, as well as the dermal penetration efficacy of the AI, and the skin carrying properties of the NLC after dermal penetration.

The properties of the NLC were compared to classical formulations, i.e., AI dissolved in pure oil, an o/w cream base and a nanoemulsion. All formulations contained similar lipids and emulsifiers, which allowed for a direct comparison of the different properties. NLC were shown to provide most efficient chemical stabilization and most efficient dermal penetration for the AI. The formation of the invisible patch was shown for the NLC but not for the other formulations. Skin hydration and skin carrying properties were also most pronounced for the NLC. Results provide evidence that NLC can combine all beneficial effects that were previously described in one formulation. Thus, providing evidence that NLC are a holistically superior formulation principle when compared to other formulation principles.

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Materials
The lipophilic fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindo-carbocyanin perchlorate (DiI perchlorate, Biozol Diagnistica Vertrieb GmbH, Germany) was chosen as a surrogate of an incorporated lipophilic AI. All formulations contained 0.005% (w/w) DiI. This concentration was chosen, because it enabled a sufficient autofluorescence for the skin penetration experiments and ensured an efficient encapsulation of the dye into the lipid phase without expulsion into the water phase at the same time. Sea fish oil (SFO) was selected as omega-3-rich liquid lipid source and was kindly provided by San Omega GmbH, Germany. Glyceryl tristearate (Dynasan^® 118, kindly provided by IOI Oleo GmbH, Germany) was used as solid lipid and structure-forming component for the o/w cream (macroemulsion, ME) and the NLC. The formulations were stabilized by using a blend of four non-ionic surfactants, i.e., Poloxamer 188 (PLX 188, kindly provided by BASF, Germany), Polysorbate 80 (Tween^® 80, VWR, Germany), Polyvinylpyrrolidone 10,000 (PVP, AppliChem GmbH, Germany), and d-α-tocopheryl polyethylene glycol 1,000 succinate (TPGS, Antares Health Products Inc., USA). The selection was based on a previous study by Muchow et al. [15]. Purified water was used as dispersion medium and was freshly obtained from a PURELAB Flex 2 (ELGA LabWater, Veolia Water Technologies Deutschland GmbH, Germany). Unless otherwise specified, all other chemicals were used as received. Table 1 provides an overview of the compositions of the formulations that were produced and characterized in this study.

About this Article: Wiemann, S., Keck, C.M. Are lipid nanoparticles really superior? A holistic proof of concept study. Drug Deliv. and Transl. Res. (2021). https://doi.org/10.1007/s13346-021-01021-5