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

Abstract

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. Graphical abstract

Influence of Massage and Skin Hydration on Dermal Penetration Efficacy of Nile Red from Petroleum Jelly—An Unexpected Outcome

“…The model uses non-modified skin that is still in its original physiological condition, i.e., it is still connected to the cartilage and thus remains in its original skin tension without any manipulation. Therefore, the model is considered as able to provide highly sensitive and sensible penetration data with high ex vivo/in vivo correlation [6][7][8][9]. For the experiments, fresh porcine ears were obtained from a local slaughterhouse and were used for the tests within 6 h after the slaughter.…”

“…The penetration efficacy was determined by assessing the amount of penetrated Nile red (AP-NR) semi-quantitatively and its mean penetration depth (MPD) into the skin by using a previously established protocol [17]. In addition, the stratum corneum thickness (SCT) was measured as a surrogate for skin hydration [6,7]. The AP and MPD were determined from the original images that were subjected to an automated RGB-threshold algorithm (Supplementary Materials S1) to subtract the autofluorescence of the skin (background, class II pixels) from the images [17].…”

“…With this, the ex vivo porcine ear model represents a highly sensitive model that allows for the determination of the penetration efficacy of chemical compounds and the detection of changes in skin conditions that occur upon treatment of the skin with the topical formulation. This combination therefore enables a more holistic view of the performance of topical formulations and should allow for the development of more effective topical products, i.e., products that provide excellent penetration for active compounds and skin-caring properties at the same time [7][8][9].…”

Cucumber-Derived Exosome-like Vesicles and PlantCrystals for Improved Dermal Drug Delivery

“…In addition, unloaded PlantCystal-PEVs and PlantCystal-PEVs to which DiI (10 nM) was added after HSS and HPH were also used as benchmark controls (Table 1). The dermal penetration efficacy was determined ex-vivo using porcine ears that were freshly obtained from a local slaughterhouse [48][49][50]. The ears were washed with lukewarm water (23-25 • C), dried with soft lint-free tissue and used directly on the day of slaughtering.…”

In vivo evaluation of nanostructured lipid carrier systems (NLCs) in mice bearing prostate cancer tumours

“…NLCs have been also used as carriers for transdermal delivery due to the increase of solubility of water insoluble drug substances [4,[6][7][8][9][10]. A dermatokinetic assessment involved the administration of luliconazole-loaded NLCs with ultra-small particle size (< 100 nm) for antifungal activity [6].…”