Transfersomes are deformable lipid vesicles extensively evaluated for transdermal drug delivery. However, the ocular penetration mechanism of transfersomes is poorly understood as the effect of tear flow, which by altering osmotic gradients across ocular tissues can influence transfersome penetration, has not been evaluated before. Hence, this study investigated the impact of simulated tear flow (STF) on the ocular distribution of curcumin-loaded transfersomes. Transfersome penetration was evaluated ex vivo under static (no STF) and dynamic (with STF) conditions and the total amount penetrated (TAP) and the maximal penetration depth (MPD) in corneal and conjunctival tissues were semi-quantitatively evaluated. Corneal distribution of transfersomes was considerably altered in the dynamic model. Drug redistribution due to STF reduced the TAP in the central cornea while increasing it in the peripheral cornea. Surprisingly, corneal MPD was significantly higher with STF, likely due to surface dehydration in the absence of STF. Meanwhile, STF reduced both TAP and MPD in the bulbar conjunctiva, although no significant difference was observed in the tarsal conjunctiva. These findings provide a mechanistic insight into ocular transfersome penetration and suggest that tear flow compromise, as observed in ocular surface disorders, may influence drug bioavailability by altering precorneal distribution and surface dehydration.

Background: Lipid nanoparticles are widely investigated as oral drug delivery systems, but their intestinal performance remains difficult to predict based only on physicochemical properties. This study aimed to elucidate how the lipid matrix composition influences the intestinal permeation of curcumin from lipid nanoparticles. Methods: Curcumin-loaded nanoemulsions, nanostructured lipid carriers with defined solid-to-liquid lipid ratios, and solid lipid nanoparticles were prepared by high-pressure homogenization. All formulations were characterized with respect to particle size, polydispersity index, and zeta potential before and after simulated intestinal pre-incubation in a simplified SDS-containing intestinal fluid. Intestinal permeation was evaluated ex vivo using porcine gut tissue by analysis of semi-quantitative fluorescence-based permeation readouts (ART) and mean permeation depth (MPD) after 30 and 60 min. Results: All formulations maintained stable physicochemical properties with particle sizes around 200 nm and negative zeta potentials; pre-incubation increased the negativity of the zeta potential but left particle size unchanged. Despite similar attributes, the formulations differed in intestinal curcumin permeation based on time and composition. At 30 min, nanoemulsions and mixed nanostructured lipid carriers achieved the highest performance. By 60 min, lipid carriers with more liquid lipid significantly increased both the fluorescence intensity and the depth of curcumin permeation, while other systems showed little further improvement. Conclusions: The intestinal permeation of drug from lipid nanoparticles is governed by the lipid matrix architecture and its interaction with the hydrated intestinal environment, which together affect drug-release kinetics and the ability to sustain a trans-epithelial concentration gradient over time. Thus, optimizing oral lipid nanoparticles requires time-resolved, biologically relevant models rather than physicochemical characterization alone, consistent with observed similar matrix-driven effects in dermal delivery systems.

Effective skin disinfection is critical in preventing surgical-site infections (SSIs), particularly during long surgical procedures where bacteria from hair follicles can continuously emerge onto the skin surface and recolonize it. To enhance follicular disinfection, this study investigates the intrafollicular delivery of isopropanol, an antiseptic agent, dissolved in the outer phase of a suspension of specifically-engineered hesperetin nanocrystals. To accurately quantify follicular penetration, we analyzed both intrafollicular concentration and penetration depth. For the former, we developed the 'hair plucking method', a novel technique that extracts whole hair follicles, comprising the hairs and their associated follicular epidermis. Using porcine ear skin as an ex vivo model, we applied two formulations: an isopropanol-based hesperetin nanocrystals suspension, and an isopropanol-based particle-free control, while a third skin area remained untreated and served as a baseline. Rhodamine 6G, a fluorescent dye, was incorporated into both formulations to track penetration. Fluorescence spectroscopy analysis of fully plucked hair follicles was employed to measure the intrafollicular concentration of the dyed antiseptic, while laser scanning microscopy of cryohistological hair follicle sections was employed to measure its penetration depth. The results showed that the nanocrystals increased intrafollicular concentration of the antiseptic formulation by over 85 % (p < 0.05) and its penetration depth by approximately 38 % (p < 0.001), demonstrating enhanced follicular delivery and validating the efficacy of the hair plucking method. These findings highlight the potential of nanoparticle-based formulations to improve surgical antisepsis and reduce SSI risks, contributing to safer and more effective preoperative disinfection strategies.

Ethanol is widely used in cosmetic formulations as a solvent, preservative, and penetration enhancer, yet its effects on atopic skin remain controversial. This study explores the impact of ethanol in skin care products on skin physiology, microbiome composition and subjective perception. A two-part investigation was conducted: (I) ex vivo analysis using porcine skin models exposed to varying ethanol concentrations, and (II) a double blinded, placebo controlled, randomized clinical pilot study on 9 patients with Atopic Dermatitis (AD) comparing creams with and without 12% ethanol. The ex vivo study revealed that ethanol concentrations above 15% negatively affected epidermal barrier integrity, increasing stratum corneum (SC) permeability and transepidermal water loss (TEWL). In the clinical trial, 12% ethanol demonstrated no significant adverse effects on SC hydration, erythema, pH, or TEWL over 30 days. Microbiome analysis revealed a localized increase in Xanthomonas species associated with ethanol use, while no significant community-wide changes were observed. The implications of increased Xanthomonas abundance in response to the application of a 12% ethanol cream for atopic dermatitis remain unclear. Subjective evaluations reported similar perceptions for both formulations, with no notable exacerbations in non-lesional AD skin. These findings indicate that ethanol in concentrations ≤ 12% is safe for atopic skin.

Background/Objectives: Burn wound infections present significant clinical challenges due to multidrug-resistant pathogens and the limitations of traditional antimicrobials. While antimicrobial peptides (AMPs) have broad-spectrum effectiveness, their instability in wound environments limits their use. This study compares properties of AMP-decorated nanostructured lipid carriers (NLCs) to free AMPs, focusing on their dermal penetration, retention, and antimicrobial efficacy in simulated ex vivo burn wound models. Methods: AMP-decorated NLCs (smart-AMPs) were produced by electrostatic and hydrophobic surface adsorption and characterized regarding their size, zeta potential, and physical short-term stability. The distribution of AMPs within the wounds was evaluated using an ex vivo porcine ear model with various wound types. The antimicrobial efficacy was assessed by monitoring the bioluminescence of Aliivibrio fischeri as a live bacterial marker for 24 h. Results: The size and zeta potential measurements confirmed the successful formation of smart-AMPs. The dermal penetration of AMPs was influenced by the type of wound and the type of AMP formulation (free AMPs vs. smart-AMPs). In the chronically infected burn wounds, which were characterized by the formation of a biofilm in a protein-rich wound fluid, the smart-AMPs resulted in a 1.5-fold higher and deeper penetration of the AMPs, and the antimicrobial activity was 6-fold higher compared to the free AMPs. Conclusions: smart-AMPs present an innovative approach for treating chronic, biofilm-associated wounds more efficiently than the current treatment options.

Due to changes in the tear fluid properties in dry eye disease (DED), eye drop performance may be altered. This study investigated the impact of tear fluid properties on the physicochemical, mucoadhesion and ocular penetration characteristics of transfersome (TFS) eye drops. Specifically, the effect of tear fluid pH and osmolarity on vesicle size, polydispersibility index (PDI) and zeta potential (ZP) of unloaded as well as curcumin- and tonabersat-loaded TFS were studied. Finally, the effect of altered tear fluid properties on corneal penetration of curcumin TFS was investigated using ex vivo porcine corneo-scleral discs. A significant increase in vesicle size and PDI was observed for curcumin and tonabersat TFS suspended in healthy and DED tears compared to water. Moreover, the ZP measured in water shifted towards neutral in the case of healthy and DED tears, suggesting reduced electrostatic stability of the vesicles. Deeper tissue penetration was observed for curcumin TFS suspended in water compared to TFS suspended in healthy tears, with significantly less penetration for TFS mixed with DED tears. This study confirmed that tear fluid properties significantly influence TFS characteristics and thus their penetration ability, highlighting the importance of evaluating ocular drug delivery systems under physiological conditions that reflect the disease state.

Background/Objective: This study provided a comparison of the influence of each component of the microemulsion formulation and investigated the impact of varying concentrations of the microemulsion components on curcumin’s ability to penetrate the skin using an ex vivo porcine ear model. Methods: Curcumin microemulsions with different compositions were prepared and analyzed for their physicochemical properties. The dermal penetration efficacy of curcumin was evaluated from the different formulations and compared with non-microemulsion formulations. Results: Findings proved that microemulsion formulations improve the dermal penetration efficacy for curcumin when compared with non-microemulsion formulations. The composition of the microemulsion affects the penetration efficacy of curcumin and increases with decreasing oil content and increasing surfactant and water content. The best penetration for curcumin is achieved with a microemulsion that contained 7.7 g of medium-chain triglycerides as the oil phase, 6.92 g of Tween® 80 and 62.28 g of ethanol as the surfactant mixture, and 23.1 g water. Conclusions: The present study provides a foundational basis for further development of different microemulsion formulations for enhancing the dermal penetration of poorly water-soluble active compounds.

(1) Background: Ethanol is a multifunctional excipient often used as a preservative in topical formulations. Due to its known ability to impair skin barrier function, this study investigated the effect of ethanol (EtOH) as a preservative in creams on the dermal penetration of active compounds. (2) Methods: A hydrophilic and a lipophilic fluorescent dye were used as active ingredient surrogates that were incorporated into creams with and without ethanol. The dermal penetration efficacy was assessed by epifluorescence microscopy on an ex vivo porcine ear model with intact and irritated skin. (3) Results: Ethanol reduced the dermal penetration by about 40% for the hydrophilic and about 20% for the lipophilic surrogates on intact skin, but had minimal impact on irritated skin. The bio-physical skin properties were also altered by the addition of ethanol to the cream. On intact skin, it increased transepidermal water loss (TEWL) and decreased skin hydration, whereas on irritated skin, it decreased TEWL and increased skin hydration. The results indicate that skin impairment can be considered to have different stages, while in an early stage of skin impairment, the formation of a “Pudding skin” is proposed. A “Pudding skin” is the formation of a thin layer of dried skin on top of the skin that “seals” the lower parts of the skin and reduces dermal penetration and water loss from inside the skin and reduces the dermal penetration of chemical compounds from outside the skin. (4) Conclusions: Overall, the findings emphasize the need to carefully consider the use of ethanol in formulations, balancing its preservative benefits with its potential to impair the efficacy of active ingredients, particularly in varying skin conditions.

Nanocrystals, defined as crystalline particles with dimensions in the nanometer range (<1000 nm), exhibit unique properties that enhance the efficacy of poorly soluble active compounds. This review explores the fundamental aspects of nanocrystals, including their characteristics and various preparation methods, while addressing critical factors that influence their stability and incorporation into final products. A key focus of the review is the advantages offered by nanocrystals in dermal applications. It also highlights their ability to enhance passive diffusion into the skin and facilitate penetration via particle-assisted dermal penetration. Additionally, the review discusses their capacity to penetrate into hair follicles, enabling targeted drug delivery, and their synergistic potential when combined with microneedles, which further enhance the dermal absorption of active compounds. The review also addresses several commercial products that successfully employ nanocrystal technology, showcasing its practical applications. Summary: Nanocrystals with their special properties are an emerging trend for dermal applications, particularly the development of plantCrystals—natural nanocrystals sourced from plant materials—which represent a promising path for future research and formulation strategies. These advancements could lead to more sustainable and effective dermal products.

Background/Objectives: PlantCrystals (PCs) are submicron particles derived from plants or parts of plants that can be produced by bead milling and/or high-pressure homogenization. Previous studies suggested improved dermal drug delivery of lipophilic active ingredients (API), which was explained by the formation of extracellular vesicles (EVs) during the production of PCs. The aim of this study was to investigate the suitability of PCs for enhancing the dermal penetration efficacy of different types of APIs. Methods: For this purpose, hydrophilic, lipophilic, and poorly water-soluble API-surrogates were loaded into PCs, and the dermal penetration efficacy, as well as the skin hydrating properties, were determined with an ex vivo porcine ear model. The penetration efficacy of the API surrogates from the PCs was compared to other formulation principles, e.g., simple API solutions, API loaded into classical EVs, and API added to the PCs after preparation. Silymarin-PCs-unloaded and loaded with API-were obtained by milling milk thistle seeds using small-scale bead milling. The PCs were characterized by size, size distribution, and zeta potential. Results: Milling of milk thistle seeds resulted in the formation of submicron particles with sizes of about 300 nm. Loaded PCs had a slightly larger size. Loading API into PCs resulted in improved dermal penetration when compared to the other formulation principles. The effect was most pronounced for the lipophilic API-surrogate (+90%, p < 0.001) and least pronounced for the hydrophilic API-surrogate (+2%, p > 0.05). The improved penetration of API from PCs can be explained by the formation of EVs during the production of the PCs in which the API is encapsulated. The encapsulation seemed to be highly efficient for the lipophilic API-surrogate, moderate for the poorly soluble API-surrogate, and very limited for the hydrophilic API-surrogate. All formulations increased the skin hydration significantly by about 30-40%. Conclusions: Milk thistle seeds are suitable for the production of PCs. These PCs improve skin hydration and enhance the dermal penetration of poorly water soluble and lipophilic APIs. However, they have limited effects on the dermal penetration efficacy of hydrophilic APIs.

Dermal drug delivery presents a significant challenge for poorly soluble active compounds like curcumin, which often struggle to penetrate the skin barrier effectively. In this study, the dermal penetration efficacy of curcumin nanocrystals and bulk suspensions when applied to skin using microneedles of varying lengths—0.25 mm, 0.5 mm, and 1.0 mm—was investigated in an ex vivo porcine ear model. The findings revealed that all formulations, in conjunction with microneedle application, facilitated transepidermal penetration; however, the combination of microneedles and curcumin nanocrystals demonstrated the highest efficacy. Notably, the 1.0 mm microneedle length provided optimal penetration, significantly enhancing curcumin delivery compared with bulk suspensions alone. Additionally, even the use of 0.25 mm microneedles resulted in a high level of efficiency, indicating that shorter microneedles can still effectively facilitate drug delivery. Overall, this study underscores the potential of microneedle technology in improving the transepidermal absorption of poorly soluble actives like curcumin, suggesting that the integration of nanocrystals with microneedles could enhance the therapeutic effects of topical curcumin applications.

The use of nanoparticulate systems for the transport of active ingredients into hair follicles has been researched for almost two decades, resulting in countless publications with a wide variety of particle types, release mechanisms and active ingredients. The production of a stable dispersion is often time-consuming and costly. In this publication, we demonstrate for the first time that simply adding diverse submicron particles to a drug solution significantly increases follicular penetration depth by over 160% to 190%, allowing the targeting of subinfundibular structures. Our results indicate that the increase in follicular penetration is independent of the type or sphericity of the particles (nanocrystals (NC) or lipid submicron particles (LN)). Furthermore, this principle can be used with both small molecules and large molecule therapeutics, as demonstrated with the model drugs fluorescein sodium, 6-carboxyfluorescein, green fluorescent protein and FITC-BSA. This highlights the high versatility of this new formulation principle. The system may be used for various hair follicle-associated diseases such as alopecia or for the preoperative disinfection of hair follicles and the transfollicular transport of active pharmaceutical and/or cosmetic ingredients.

AIM:To develop medicinal plant nanoparticles as colitis alternative/supplementary therapy. BACKGROUND:Limited reports exist on the effectiveness of medicinal plant nanocrystals in treating or preventing colitis. OBJECTIVES:We investigated the effect of canonizing Apium graveolens (AG) on improving dextran sodium sulfate (DSS)- induced (4%) colitis. METHODS:Nanonization was performed via the bead milling process. The nanocrystal product was characterized (i.e., particle size, zeta potential (ZP), polydispersity index (PDI) values) and freezedried. Total flavonoids and phenolic compounds in nanocrystal products were compared with ethanolic extract of AG (AGEE). Anti-colitis activity of AG-nanocrystal water suspensions (AGNS) was compared to AG bulk powder suspensions (AGBS). Colitis severity was determined via physiological, macroscopic, and microscopic colon assessment. In addition, the fecal Enterobacteriaceae population and urine glucose levels were determined. RESULTS:The AG nanoparticle products are 200-400 nm, with PDI values 0.5-0.6, and ZP values -12 to -20 mV. The total flavonoid and phenolic compounds of AGNS were 115.12±4.32 ppm and 37.11±0.34 ppm, respectively. This value is higher compared to the content in AGEE. AGNS (350 mg/kg) improves physiological (i.e., fecal blood), macroscopic (i.e., length, diameter), and microscopic (i.e., structure and immune cell infiltration) colon conditions in a comparable level to the positive control of 5-aminosalicylic acid (100 mg/kg). AGNS have a compelling ability to restore colon microscopic and Enterobacteriaceae population compared to AGBS (700 mg/kg). AGNS (350 mg/kg) also recovered colon permeability as marked by the lower urine glucose concentration (9.90±0.15 mg/dL) compared to colitis mice (12.43±0.09 mg/dL). CONCLUSION:The nanonization of AG contributes to improved anti-colitis activities compared to AGBS. Nanonization of medicinal plants will reduce organic solvent extraction, which supports the sustainable development goals.

Hair follicles have recently emerged as promising drug delivery targets and gates for skin penetration. The so-called ratchet effect, which is based on an interaction between the hair shaft surface, the intrafollicular stratum corneum and nanoparticles, has proven to be very effective for the transport of active ingredients. Especially the nanoparticle-assisted decolonization of hair follicles constitutes an interesting new area of application. In a recently published work it was shown that small molecules as well as macromolecules solved in an outer phase of a formulation can be transported into the deeper parts of the hair follicles by adding nanoparticles to the formulation. In this case the nanoparticles constitute an entity independent of the drug and the transport is hypothesized to be based on an adhesion effect. In the present work, we focused on the impact of the particle concentration in the formulation on the transport efficiency of the model drug fluorescein sodium into hair follicles utilizing an ex vivo porcine skin model. It was observed that a particle concentration of 4

Rational Nickel is one of humans' most prevalent triggers of allergic contact dermatitis. However, the underlying mechanisms of this allergy still need to be fully understood. One aspect that has yet to be explored is the direct impact of common metal allergens on the skin's metabolites and lipids composition. Method Our study employed matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) to analyze spatially resolved metabolic alterations induced by nickel exposure. Cross‐sections of ex vivo porcine ear skin exposed to increasing nickel (II) ion concentrations (17–167 μg/cm 2 ) were measured with an AP‐SMALDI 5 AF ion source coupled to Q Exactive HF Orbitrap mass spectrometer. Additionally, the penetration of nickel ions into the skin was observed through its pink complexation with dimethylglyoxime under light microscopy. Results For nickel ion concentrations up to 84 μg/cm 2 , most nickel ions were stopped within the stratum corneum, while only a very small proportion of nickel ions penetrated the viable epidermis and dermis. Stratum corneum locations with high nickel ion concentrations showed a decrease in arginine and ceramides. Furthermore, several phosphatidylcholine and sphingomyelin species were found to be downregulated in the viable epidermis and dermis due to the nickel exposure. Conclusion Nickel penetrates at a trace level into the viable skin and induces severe metabolomic and lipidomic changes in the stratum corneum, epidermis, and dermis, indicating a change in the skin (barrier) function. These findings contribute to a deeper understanding of nickel‐induced skin allergies and provide a solid foundation for further research.

Objective: This study aimed to investigate the feasibility of using the digital image processing technique, developed to semi-quantitatively study dermal penetration, to study corneal penetration in an ex vivo porcine eye model. Here, we investigated various formulation strategies intended to enhance dermal and corneal bioavailability of the model hydrophobic drug, curcumin. Methods: Several formulation principles were explored, including oily solutions, oily suspensions, aqueous nanosuspension, micelles, liposomes and cyclodextrins. The dermal penetration efficacy was tested using an ex vivo porcine ear model previously developed at Philipps-Universität Marburg with subsequent digital image processing. This image analysis method was further applied to study corneal penetration using an ex vivo porcine whole-eye model. Results: For dermal penetration, oily solutions, oily suspensions and nanosuspensions exhibited the least penetration, whereas liposomes and cyclodextrins showed enhanced penetration. Corneal curcumin penetration correlated with dermal penetration, with curcumin loaded into cyclodextrins penetrating the deepest. Conclusions: Overall, our study suggests that the image analysis method previously developed for ex vivo skin penetration can easily be repurposed to study corneal penetration of hydrophobic drugs.

The limited water solubility of active compounds remains a significant challenge for efficient dermal drug delivery, particularly for BCS class IV drugs such as curcumin. This study aimed to enhance curcumin’s dermal penetration using two strategies: extracellular vesicles (EVs) and plantCrystals derived from soybeans. EVs were isolated using classical methods. However, plantCrystals containing extracellular vesicles (PCEVs) were formed during the preparation of plantCrystals through bead milling. Curcumin was either added after PCEVs were formed, resulting in curcumin-added PCEVs, or added to the soybean dispersion before bead milling, forming curcumin-loaded PCEVs. The formulations were characterized for their physicochemical properties and assessed for dermal penetration efficacy using quantitative dermatokinetic and semi-quantitative ex vivo porcine ear models. The results indicated that curcumin-loaded PCEVs achieved higher penetration efficacy compared to curcumin-added PCEVs and curcumin-loaded EVs, with approximately 1.5-fold and 2.7-fold increases in penetration efficacy, respectively. Additionally, curcumin-loaded PCEVs showed superior penetration depth, while curcumin from the curcumin-loaded EVs remained in the stratum corneum. These findings suggest that the plantCrystals strategy via bead milling offers a more effective approach than the classical EVs strategy for improving the topical delivery of class IV drugs like curcumin.

The influence of the vehicle on the dermal penetration efficacy of three different active ingredient (AI) surrogates (hydrophilic, amphiphilic, lipophilic model drugs), that were incorporated into these vehicles, was investigated with the ex vivo porcine ear model, which allowed to assess time and space resolved dermal penetration profiles of the AI. Fifteen different vehicles, including classical vehicles (hydrogel, oleogel, o/w cream, w/o ointment, amphiphilic cream) and innovative vehicles were included into the study. Results show tremendous differences in the penetration efficacy of the AI among the different vehicles. The differences in the total amounts of penetrated AI between lowest and highest penetration were about 3-fold for the hydrophilic AI surrogate, 3.5fold for the amphiphilic AI and almost 5-fold for the lipophilic AI. The penetration depth was also affected by the type of vehicle. Some vehicles allowed the AI to penetrate only into the upper layers of the stratum corneum, whereas others allowed the penetration of the AI into deeper layers of the viable dermis. Data therefore demonstrate that the vehicles in compounding medications cannot be exchanged against each other randomly if a constant and safe medication is desired. The data obtained in the study provide first information on which types of vehicles are exchangeable and which types of vehicles can be used for enhanced dermal penetration of AI, thus providing a first base for a science-based selection of vehicles that can provide both, efficient dermal drug delivery and skin barrier function maintenance/strengthening at the same time.

BACKGROUND:Transferosomes (TFS) are ultra-deformable elastic bilayer vesicles that have previously been used to enhance gradient driven penetration through the skin. This study aimed to evaluate the potential of TFS for topical ocular drug delivery and to compare their penetration enhancing properties in different ocular tissues. METHODS:Curcumin-loaded TFS were prepared using Tween 80 as the edge activator. Drug release and precorneal retention of the TFS were evaluated in vitro, while their ocular biocompatibility and bioavailability were evaluated ex vivo using a curcumin solution in medium chain triglycerides as the oily control. RESULTS:The TFS had a narrow size distribution with a particle size less than 150 nm and an entrapment efficiency greater than 99.96 %. Burst release from the TFS was minimal and the formulation showed good corneal biocompatibility. Moreover, enhanced corneal and conjunctival drug penetration with significantly greater and deeper drug delivery was observed with TFS. CONCLUSION:TFS offer a promising platform for ocular delivery of hydrophobic drugs. This study, for the first time, elucidates the effect of tissue morphology and osmotic gradients on drug penetration in different ocular tissues.

Curcumin is a biopharmaceutical classification system (BCS) class IV substance with many potential therapeutic effects. However, like many other BCS IV active pharmaceutical ingredients, complex formulations are needed to guarantee a sufficiently high bioavailability. A not-so-well-known delivery system is a suspoemulsion (SE). SEs are emulsions with a crystalline API in continuous or dispersed phases. This study aimed to produce curcumin-loaded o/w suspoemulsions with the particle in the oil phase for, e.g., encapsulation or triggered release effects. The particles need to be smaller than the emulsion droplet size to attain high encapsulation efficiencies (EE) in the oil phase. Sonofragmentation and bead milling were tested for their ability to produce these nanocrystals in different dispersion media. It was discovered that production in miglyol was the best fit for the needed application of the crystals in SEs. Around 85% (by volume) of the particles produced with bead milling were smaller than the droplet size of about 5 µm. In contrast, only 23% of the sonofragmentated particles were below the diameter of those droplets. This oily suspension was then used to successfully produce hydrogel-based o/w suspoemulsions. In the second part of this study, we investigated different methods for determining encapsulation efficiency, but none of the methods accurately and satisfactorily resolved the encapsulation efficiency. Finally, the suspoemulsions could not be macroscopically distinguished from one another and were physically stable. In summary, we showed that stable hydrogel-based curcumin-loaded o/w suspoemulsions could be produced.