Spontaneous Emulsification Research Articles

Preparation and Properties of Temperature-Sensitive P(NIPAM-AM) Nano–Microspheres in Enhanced Oil Recovery

As a new kind of water plugging and profile control agents, the polyacrylamide nano–microspheres have been experimentally applied and achieved satisfactory preliminary results in enhanced oil recovery, especially for low-permeability reservoirs. However, the larger swollen particle size and excessive hydrophilicity limit the effect at the oil–water interface. In order to further improve their profile control and flooding effect, the temperature-sensitive poly(N-isopropylacrylamide-acrylamide) nano–microspheres are prepared by inverse microemulsion polymerization. Based on the principle of conformation transition of PNIPAM triggered by simulated high temperature in reservoirs, the particle size and hydrophilicity of the microspheres are reduced, making it easier to reach the oil–water interface, reduce the oil–water interface tension, and enhance the structural disjoining pressure, which improves the spontaneous emulsification effect and removal effect of residual oil on rocks. The swelling properties, hydrophilicity, interfacial activity, and oil displacement properties of the nano–microspheres were also analyzed. The results show that the swelling ratio of the copolymerized nano–microspheres decreases to 1.5. At simulated reservoir temperature (65 °C), the water contact angle of copolymerized gel increases from 43 to 86°, indicating that its hydrophilicity decreases and shows a clear tendency to migrate to the water–oil interface. At 65 °C, 0.1 wt % PNIPAM-based microsphere emulsion (N3) reduces the oil–water interfacial tension from 17.8 to 0.9 mN m–1. The microscopic oil displacement experiment shows that the recovery efficiency of our designed temperature-sensitive nano–microspheres emulsion is increased by 7%, which is higher than that of the PAM polymer nanosphere. The PNIPAM-based temperature-sensitive nano–microspheres that can function at the oil–water interface have a potential development prospect in low-permeability reservoirs.

Effect of Hydrogel Containing Achyrocline satureioides (Asteraceae) Extract–Loaded Nanoemulsions on Wound Healing Activity

Achyrocline satureioides (Lam.) DC extract-loaded nanoemulsions have demonstrated potential for wound healing, with promising effects on keratinocyte proliferation. We carried out the first in vivo investigation of the wound healing activity of a hydrogel containing A. satureioides extract-loaded nanoemulsions. We prepared hydrogels by adding the gelling agent (Carbopol® Ultrez) to extract-loaded nanoemulsions (~250 nm in diameter) obtained by spontaneous emulsification. The final flavonoid content in formulation was close to 1 mg/mL, as estimated by ultra-fast liquid chromatography. Permeation/retention studies using porcine ear skin showed that flavonoids reached deeper layers of pig ear skin when it was damaged (up to 3.2 µg/cm² in the dermis), but did not reach the Franz-type diffusion cell receptor fluid. For healing activity, we performed a dorsal wound model using Wistar rats, evaluating the lesion size, anti-inflammatory markers, oxidative damage, and histology. We found that extract-loaded formulations promoted wound healing by increasing angiogenesis by ~20%, reducing inflammation (tumor necrosis factor α) by ~35%, decreasing lipid damage, and improving the re-epithelialization process in lesions. In addition, there was an increase in the number of blood vessels and hair follicles for wounds treated with the formulation compared with the controls. Our findings indicate that the proposed formulation could be promising in the search for better quality healing and tissue reconstruction.

A review article: Drug delivery systems, preparation techniques, and biological applications using nanoemulsion as a novel platform

Nanotechnology, particularly nanoemulsions (NEs), is an essential topic that has piqued the interest of researchers over the years. These significant molecules feature a spherical solid structure, a lipophilic amorphous negative charge surface, with small droplet size, and a large surface area, all of which contribute to the promising future of nanomedicine and the importance of NEs in a variety of sectors. The advantages and disadvantages of the components, preparation, characterization, assessment, and applications as a delivery medication system are summarized in this review paper. There are two different methods for NEs preparation: the high and low energy methods. In high energy methods, high-pressure homogenization, ultrasonication micro fluidization, and Spontaneous emulsification are described thoroughly. Low energy approaches emphasize phase inversion temperature, solvent evaporation technology, and hydrogel technologies. Low-energy procedures should be preferred over high-energy methods since they utilize less energy and do not necessitate the use of specific instruments. The transdermal application, aerosolized, ingestible NEs, and parenteral techniques are the four primary lines of biomedical uses of NEs as a delivery strategy. To summarize, these novel strategies are very promising, but additional research is needed to fully understand the relationship between NE formulation and physiological and pathological problems associated with diverse preparation, characterization, and administration routes.

Preparation and characterization of geraniol nanoemulsions and its antibacterial activity.

Geraniol nanoemulsions (G-NE) based on Tween 80 and medium chain triglyceride (MCT) as surfactant and co-surfactant, respectively, has been prepared by the spontaneous emulsification method. Its physical and chemical properties such as mean particle size, zeta potential, PDI, pH, viscosity, contact angle, appearance morphology, and stability (storage stability, thermal stability, centrifugal properties, acid-base stability, and freeze-thaw properties) of the droplet were analyzed. The results showed that the mean particle size of G-NE was 90.33 ± 5.23 nm, the PDI was 0.058 ± 0.0007, the zeta potential was -17.95 ± 5.85 mV and the encapsulation efficiency was >90%. The produced G-NE has been demonstrated to be fairly stable in long-term storage at 4°C, pH = 5 and high-speed centrifuges. Moreover, G-NE had a significant inhibition effect on Staphylococcus aureus, Escherichia coli, Salmonella typhimurium and Listeria monocytogenes (p < 0.05). The bacterial inhibition rates of G-NE at a concentration of 1 MIC were 48, 99, 71.73, and 99% after 12 h of action against these four foodborne pathogenic bacteria, respectively. Therefore, the results obtained indicated that nanoemulsification enhanced the stability and antibacterial activity of geraniol to some extent, which will promote the utilization of geraniol in food preservation.

FORMULATION AND CHARACTERIZATION OF ZEAXANTHIN NANOEMULSION RADIANCE SERUM AS ANTIOXIDANT

Objective: This study aimed to increase the effectiveness of using zeaxanthin by developed nanoemulsion containing zeaxanthin which was then formulated into radiance serum for topical use.&#x0D; Methods: Nanoemulsions are made using spontaneous nano emulsification methods/techniques, which are relatively simple technologically because they rely on the right combination of selected surfactants and co-surfactants. The optimization of the formula was carried out starting from determining the oil: surfactant: co-surfactant phase ratio and concentration of zeaxanthin. Nanoemulsion characterization in the form of physical characterization includes organoleptic tests, globule size and polydispersity index, zeta potential, pH and entrapment efficiency tests. The best results from nanoemulsion were then combined into serum preparations which were then tested for evaluation of the preparations, including organoleptic, homogeneity, viscosity, pH, spreadability, and antioxidant test.&#x0D; Results: The results showed that the developed zeaxanthin nanoemulsion had a globule size in the range of 20-24 nm (with a normal globule size distribution curve), polydispersity index value of less than 0.3, zeta potential greater than (-20) mV and entrapment efficiency ranging from 80-85%.&#x0D; Conclusion: The results of the evaluation showed that the serum radiance of zeaxanthin nanoemulsion had good physical, chemical and stability properties during storage with an IC50 value of zeaxanthin less than 50 ppm.

In vitro evaluation of NA1-115-7-loaded nanoemulsions, an MCL-1-specific inhibitor of natural origin, intended to treat B-cell lymphoproliferative disorders after oral administration

MCL-1, an anti-apoptotic member of the BCL-2 protein family, is overexpressed in many types of cancer and contributes to chemotherapy resistance. The drimane derivative NA1-115-7 is a natural compound isolated from Zygogynum pancheri that can be considered as a very promising lead for treating MCL-1-dependent hematological malignancies. As this drug suffers from low stability in acidic conditions and poor aqueous solubility, we evaluated the potential oral use of NA1-115–7 by encapsulating it in lipid nanoemulsions (NA-NEs) prepared by spontaneous emulsification. NA-NEs showed a particle size of 41.9 ± 2.2 nm, PDI of 0.131 ± 0.016, zeta potential of –5.8 ± 3.4 mV, encapsulation efficiency of approximately 100 % at a concentration of 24 mM. The stability of NA-1–115–7 was sixfold higher than that of the unencapsulated drug in simulated gastric fluid. NA-NEs significantly restored apoptosis and halved the effective doses of NA1-115–7 on BL2, a Burkitt lymphoma cell line, without toxicity in normal cells. Such a drug-delivery system appears to be particularly interesting for the oral administration of NA1-115–7, as it improves its solubility and stability, as well as efficacy, by reducing the therapeutic dose, making it possible to further consider in-vivo studies of this promising drug in BL2 xenografted mice.

Investigations on the enhanced oil recovery capacity of novel bio-based polymeric surfactants

Chemical enhanced oil recovery (cEOR) remains one of the most potent tertiary recovery methods. However, because of the complexity, cost, and environmental risks, attention is shifting towards bio-based polymeric surfactants as a possible alternative. Due to its vast abundance, cellulose has been identified as a source and cheap means of developing bio-based chemicals for oil recovery. In this study, novel hydrophobically modified cellulose sulphates, DPEA-Cell-OSO3−I (D-I) and DPEA-Cell-OSO3−II (D-II), were synthesized via microwave-assisted REDOX-mediated free-radical random copolymerization. Molecular characterization using nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) revealed their unique molecular features. In particular, D-II is identified as a mesoporous material. Rheological studies carried out on an economic concentration range of 50 to 1500 ppm showed that the novel products have moderate thickening properties, with viscosities less than 100 cP. Furthermore, it was discovered that the fluids are thermo-viscosifying and dilatant as well. Interfacial tension investigations revealed that they are surface-active with interfacial tension (IFT) lowering profiles improving with temperature as well, dropping down to the levels of 0.01 mN/m for D-I. They also demonstrated strong emulsifying capacity as Windsor types –II, +II, and middle phase microemulsion type III were produced during spontaneous emulsification tests. During coreflooding, D-I and D-II attained recoveries of 36 % and 53 %, respectively, over waterflood. D-II in particular had a very high residual resistant factor of 80, which is attributed to its dilatant nature, and emulsifying capabilities. In all, the properties and performances of the novel cellulose sulphate derivatives were linked to their molecular structures and architectures. Most importantly, these bio-based EOR materials will be suitable for high-temperature reservoirs.

Shedding light on the formation and stability of mesostructures in ternary “Ouzo” mixtures

Hypothesis: Ternary systems made of water, a water-miscible solvent, and hydrophobic solutes spontaneously produce metastable particles by the “Ouzo effect” and thermodynamically stable “Surfactant-Free Micro Emulsions” (SFME). However, the use of different analyses has led to a variability in the criteria to determine the boundaries of the Ouzo domain. We hypothesized that this could be clarified by investigating the stability and the physical state of the particles.Experiments: We investigate four systems using both solid and liquid solutes and two different solvents, and achieved a careful investigation of their phase diagrams, using DLS, Nanoparticle Tracking Analysis, NMR, Multiple Light Scattering, electrophoretic mobility, and fluorescence analysis.Findings: Our results evidence that the transition from the monophasic to the Ouzo domains does not coincide with the cloudiness curve, and that compositions in the Ouzo domain can look fully transparent, in contrast to what is often considered. This transition is best determined by stability analysis. The cloudiness curve corresponds to the formation of particles with a large size dispersity. In the Ouzo domain, we observed an exchange of solute between the continuous phase and solute particles swollen with solvent. In addition, the particles are stabilized against coalescence by their high negative charge.

Controlled Fabrication of Carbon Nanotube Microspheres from Emulsion Templates: Exploring the Dynamics of Solvent Loss and Nanoparticle Assembly

AbstractThe use of emulsions as templates for nanomaterial assembly is a versatile method to create controlled microstructures. However, production rates are often low, particularly where the droplet phase solvent must be removed to achieve consolidation. Here, the emulsion templated fabrication of microparticles from multi‐walled carbon nanotubes (CNTs) is studied. As an exemplar primary nanoparticle for microparticle assembly, CNTs present particular challenges due to their strong inter‐particle interactions and limited dispersion in solvents. Nevertheless, small batches of CNT microparticles have demonstrated promising performances in energy storage, environmental remediation, and sensing due to their controlled structures. Improving CNT microparticle production through emulsion processing is therefore interesting to promote these real‐world applications. In this work, it is shown that the slow rate of CNT microparticle formation from water‐in‐oil emulsions is due to spontaneous emulsification. Then methanol‐in‐oil emulsions are tested, which rapidly form fragile CNT capsules. Using mixtures of methanol and water, a faster rate of solvent loss can be balanced alongside nanoparticle assembly; CNT microparticle formation is up to twice as fast using 40% methanol compared to aqueous dispersions. In addition to facilitating faster CNT microparticle production, these findings offer more broadly applicable insights into the mechanisms of solvent transport in emulsions.

Special Issue “Micro/Nano Emulsions: Smart Colloids for Multiple Applications”

Microemulsions are known as thermodynamically stable nanodispersions driven by spontaneous emulsification and are commonly prepared as transparent mixtures composed of oil, water, a surfactant, and a cosurfactant [...].

Quantifying the spontaneous emulsification of a heavy hydrocarbon with the presence of a strong surfactant

The rate of spontaneous emulsification phenomenon of heavy hydrocarbon in a non-ionic surfactant solution was studied experimentally. The size of a diminishing oil droplet was monitored photographically with the presence of an electrolyte. The obtained data were analysed using Axisymmetric Drop Shape Analysis (ADSA) software to measure the flux of emulsion droplets formed spontaneously. In contrast to all previous reports, a stable layer confined between the oil and aqueous solution was observed with a relatively constant thickness, ∼ 100 µm. The result shows that the rate of emulsification is reduced with the presence of electrolytes and is inversely correlated to its concentration. Considerable variation of the influence of electrolyte type on the kinetic of the spontaneous emulsification process for a given condition has been observed. Consequently, a new diffusion-control mechanism has been proposed, creating an extendable model to describe the process theoretically. The experimental data of emulsifying hexadecane in Triton X-100 micellar solution with the presence of potassium chloride and sodium chloride was well fitted to the proposed model. The results have important implications for surfactant-based cleaning processes.

Curcumin nanoemulsion counteracts hepatic and cardiac complications associated with high-fat/high-fructose diet in rats.

The relationship between the incidence of cardiovascular abnormalities and non-alcoholic fatty liver disease (NAFLD) has long been postulated. Curcumin (CUR) is a potential anti-atherosclerotic agent but its poor water solubility hinders its pharmacological use. Therefore, the present study aimed to investigate the effect of formulation of CUR nanoemulsion prepared using the spontaneous emulsification technique on high fat high fructose (HFHF)-induced hepatic and cardiac complications. Fifty Wistar rats were divided into five groups. CUR nanoemulsion at doses of 5 and 10mg/kg and conventional powdered CUR at a dose of 50 mg/kg were orally administered daily to rats for two weeks, and compared with normal control and HFHF control. Results revealed that the high dose level of CUR nanoemulsion was superior to conventional CUR in ameliorating the HFHF-induced insulin resistance status and hyperlipidemia, with beneficial impact on rats' recorded electrocardiogram (ECG), serum aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels, leptin, adiponectin, creatine phosphokinase, lactate dehydrogenase and cardiac troponin-I. In addition, hepatic and cardiac oxidative and nitrosative stresses, oxidative DNA damage and disrupted cellular energy statuses were counteracted. Results were also confirmed by histopathological examination. PRACTICAL APPLICATIONS: The use of curcumin nanoemulsion could be beneficial in combating hepatic and cardiac complications resulting from HFHF diets.

Influence of Surfactant Concentration on Spontaneous Emulsification Kinetics

The kinetics of spontaneous emulsification is investigated on aqueous pendant drops in paraffin oil. Optical microscopy in transmission mode is used for high-spatial-resolution image recording. The influence of a lipophilic surfactant (Span 80) and two water-soluble surfactants (CTAB and SDS) is investigated. As time runs, the drop interface turns opaque due to the formation of microstructures associated with spontaneous emulsification. The time evolution of this phenomenon is shown to depend upon temperature and surfactant concentration, which leads to an overall shrinkage due to gradual water uptake and transport into paraffin oil. Spontaneous emulsification kinetics depends upon the chemical composition. Higher concentrations of Span 80 and CTAB (resp. SDS) are shown to promote (resp. hinder) water transport. This work provides new insights into the understanding of spontaneous emulsification when combining the properties of non-ionic and ionic surfactants.

PEGylation of Nanoemulsion Using Spontaneous Emulsification Method.

Nanoemulsion (NE), a lipid-based drug delivery system, plays an important role in delivering drugs and enhancing bioavailability. They are mainly taken up by the reticuloendothelial system, because of which their bioavailability is diminished, leading to poor therapeutic activity. It is important to protect this delivery system using a coating agent. Thus, we have coated o/w type NE using polyethylene glycol (PEG). The novelty in our study is use of dicarboxylic acid-linked PEG. Furthermore, the spontaneous emulsification method was used in preparation and peg coating, not mentioned previously. After the preparation of NE, various characterization and stability studies were carried out. We have also optimized the ratios for NE and PEG NE by using various concentrations of Smix, PEG, and water. Also, the same has also been plotted in a pseudoternary-phase diagram. As a conclusion, the PEGylation of NE was carried out successfully and may also be used for linking with other ligands because of the presence of COOH group.

Bedaquiline fumarate microemulsion: formulation optimization, rheological characterizationand in vitro studies.

Aim: Bedaquiline fumarate (BQF), an antitubercular drug, shows limited bioavailability due to solubility-limited intestinal absorption. In this research,the authorsformulated aBQF-loaded microemulsion to improve BQF's oral bioavailability. Methods: Microemulsion was prepared by a spontaneous emulsification method and evaluated for thermodynamic stability, size, dispersibility, transmittance, rheology, microrheology, drug release, cytotoxicityand cellular uptake. Results: Microemulsion showed an average globule size of 26.50±6.29nm with spherical geometry and revealed gel-sol-gel behavior in microrheological studies. Cytotoxicity and cell uptake studies in Caco-2 cells showed that BQF microemulsion was cytocompatible at the highest concentration of 500μg/mlwith significantly higher cellular uptake than control. Conclusion: The present study indicates that BQF microemulsion could be explored further for effective treatment of multidrug-resistant tuberculosis.

Nanoemulsified Genistein and Vitamin D Mediated Epigenetic Regulation to Inhibit Osteoporosis.

The imbalance in the bone remodeling process with more bone resorption by osteoclasts compared to bone formation by osteoblasts results in a metabolic bone disorder known as osteoporosis. This condition reduces the bone mineral density and increases the risk of fractures due to low bone mass and disrupted bone microarchitecture. Osteoclastogenesis increases when the receptor activator NFκB ligand (RANKL) on the osteoblast surface binds to the receptor activator NFκB (RANK) on the osteoclast surface and the function of the decoy receptor of RANKL, osteoprotegrin, is compromised due to external stimuli such as heparin and lipopolysaccharides. The RANK/RANKL axis promotes the nuclear factor kappa B (NFκB) expression, which in turn increases the histone methyltransferase activity of EzH2 and EzH1 for the epigenetic regulation of osteoclastogenesis-related genes. Genistein counteracts NFκB-induced osteoclastogenesis and downstream signaling through the direct regulation of histone methyltransferase, EzH2 and EzH1, transcription. However, genistein possesses limitations like low bioavailability, low water solubility, high estrogen activity, and thyroid side effects, which obstruct its therapeutic usage. Here, the nanoemulsified formulation of genistein with vitamin D was utilized to circumvent the limitations of genistein so that it can be utilized for therapeutic purposes in osteoporosis management. The nanoemulsification of genistein and vitamin D was performed through the spontaneous emulsification using Tween 80 and medium chain triglyceride oil as an organic phase. The physiologically stable and biocompatible combination of the genistein and vitamin D nanoemulsion (GVNE) exhibited the controlled release pattern of genistein with Korsmeyer-Peppas and Higuchi models under different pH conditions (7.4, 6.5, and 1.2). The GVNE potentially enhanced the therapeutic efficacy under in vitro osteoporosis models and helped restore disease parameters like alkaline phosphatase activity, tartrate-resistant acid phosphatase activity, and the formation of multinuclear giant cells. Molecularly, the GVNE overturned the LPS-induced osteoclastogenesis by downregulation of NFκB expression along with its binding on EzH2 and EzH1 promoters. GVNE effects on the osteoporosis model established it as an efficient antiosteoporotic therapy. This nanonutraceutical-based formulation provides an epigenetic regulation of osteoporosis management and opens new avenues for alternate epigenetic therapies for osteoporosis.

Liposome and microemulsion loaded with ibuprofen: from preparation to mechanism of drug transport

To compare the difference between liposome (LP) and microemulsion (ME) in delivering ibuprofen (IBU) transdermally and explore relative mechanism. IBU-LP and IBU-ME were prepared by ethanol injection and spontaneous emulsification, respectively. The percutaneous delivery was evaluated using Franz diffusion cells. Fourier transform infra-red spectroscopy (FTIR), differential scanning calorimetry (DSC), activation energy (Ea), and confocal laser scanning microscopy (CLSM) were used to investigate the transdermal mechanism. The particle size and encapsulation efficiency were 228.00 ± 8.60 nm, 86.68 ± 1.43%(w/w) for IBU-LP, and 56.74 ± 7.11 nm, 91.08 ± 3.27%(w/w) for IBU-ME. Percutaneous study showed that formulations enhanced permeation and drug retention in the skin. FTIR and DSC showed that the permeation occurred due to the interaction of the formulations with the lipid bilayer and the protein. The decrease in Ea (1.506 and 0.939 kcal/mol) revealed that the stratum corneum (SC) lipid bilayers were significantly disrupted and this destructive effect of IBU-LP was stronger. IBU-LP was superior to IBU-ME in the aspects of transdermal delivery of IBU.

Investigation of Factors Influencing Formation of Nanoemulsion by Spontaneous Emulsification: Impact on Droplet Size, Polydispersity Index, and Stability.

Interest in nanoemulsion technology has increased steadily in recent years for its widespread applications in the delivery of pharmaceuticals, nutraceuticals, and cosmeceuticals. Rational selection of the composition and the preparation method is crucial for developing a stable nanoemulsion system with desired physicochemical characteristics. In the present study, we investigate the influence of intricate factors including composition and preparation conditions that affect characteristic parameters and the stability of the nanoemulsion formation prepared by the spontaneous emulsification method. Octanoic acid, capryol 90, and ethyl oleate were selected to represent oil phases of different carbon–chain lengths. We explored the impact of the addition mode of the oil–Smix phase and aqueous phase, vortexing time, Km (surfactant/cosurfactant) ratio, and the replacement of water by buffers of different pH as an aqueous system. The phase behavior study showed that the Smix phase had a significant impact on the nanoemulsifying ability of the nanoemulsions composed of oil phases of varying carbon-chain lengths. The mode of mixing of the oil–Smix phase to the aqueous phase markedly influenced the mean droplet size and size distribution of the nanoemulsions composed of oil phases as capryol 90. Vortexing time also impacted the mean droplet size and the stability of the generated nanoemulsion system depending on the varying carbon-chain length of the oil phase. The replacement of the water phase by aqueous buffers of pH 1.2, 5.5, 6.8, and 7.4 has altered the mean droplet size and size distribution of the nanoemulsion system. Further, the Km ratio also had a significant influence on the formation of the nanoemulsion system. The findings of this investigation are useful in understanding how the formulation composition and process parameters of the spontaneous emulsification technique are responsible for affecting the physicochemical characteristics and stability of the nanoemulsion system composed of oil of varying carbon-chain (C8-C18) length.

Development of the Pretreatment Method for Trace Analysis by Using Spontaneous Emulsification

Development of the Pretreatment Method for Trace Analysis by Using Spontaneous Emulsification

In vitro 3D malignant melanoma model for the evaluation of hypericin-loaded oil-in-water microemulsion in photodynamic therapy

Advances in biomimetic three-dimensional (3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional (2D) cell culture. Gelatin methacryloyl (GelMA) is widely used as a tissue-engineered scaffold hydrogel for 3D cell culture. In the present study, an in vitro 3D malignant melanoma model based on GelMA was fabricated to evaluate the efficiency of hypericin (Hy)-loaded microemulsion (ME) in photodynamic therapy against melanoma. The ME was produced by the spontaneous emulsification method to enhance the bioavailability of Hy at tumor sites. Hy-loaded MEs were applied to a 3D malignant melanoma model made using 6% GelMA and the co-culture of B16F10 and Balb/c 3T3 cells, followed by crosslinking using violet light (403 nm). The observation revealed excellent cell viability and the presence of F-actin cytoskeleton network. Hy-loaded MEs exhibited higher phototoxicity and cell accumulation (about threefold) than free Hy, and the cells cultured in the 3D system displayed lower susceptibility (about 2.5-fold) than those in 2D culture. These findings indicate that the developed MEs are potential delivery carriers for Hy; furthermore, GelMA hydrogel-based modeling in polydimethylsiloxane (PDMS) molds is a user-friendly and cost-effective in vitro platform to investigate drug penetration and provide a basis for evaluating nanocarrier efficiency for skin cancer and other skin-related diseases.