Low Solubility Limit Research Articles

Fabrication of interfacial crystallized oleogel emulsion for quercetin delivery with enhanced environmental stability and bioaccessibility.

Quercetin is a flavonoid compound with numerous bioactivities. However, the low solubility, easy degradation and low bioaccessibility limit its application. In this study, a novel interfacial crystallized oleogel emulsion was fabricated, where beeswax was used as the oleogelator, for quercetin encapsulation with enhanced stability and bioaccessibility. The process of interfacial crystallization was investigated using interfacial rheology and polarized microscopy, with a positive correlation between crystal density and beeswax content in the oil phase. Emulsion stability was directly linked to beeswax concentration in the oil phase, with 100 mg g-1 showing enhanced stability under storage, UVB light exposure and ionic conditions. Beeswax addition significantly increased the quercetin loading capacity of the emulsion; particularly, at a 200 mg g-1 beeswax concentration, the loading capacity was improved by 285.55%, and the environmental stability was enhanced against UV light and Ca2+. Ultimately, in vitro simulated digestion experiment indicated improved bioaccessibility of quercetin. This strategy significantly enriched the formulation of oleogel emulsion and its potential applications in delivering bioactive ingredients with high environmental vulnerability. © 2024 Society of Chemical Industry.

Exploring the Interaction of Lipid Bilayers with Curcumin-Laponite Nanoparticles: Implications for Drug Delivery and Therapeutic Applications.

Curcumin, the active compound in turmeric, is renowned for its anti-inflammatory, antioxidant, and antimicrobial properties, making it beneficial for treating conditions like arthritis, neurodegenerative diseases, and various cancers. Despite its promising therapeutic potential, curcumin's poor bioavailability-due to its rapid metabolism and low solubility-limits its clinical efficacy. To address this, recent research has focused on enhancing curcumin delivery using nanoparticles, liposomes, and novel nanomaterials. Among these, laponite, a synthetic nanoclay, has shown promise in improving curcumin delivery due to its unique properties, including large surface area, dual charge, and stability in solution. This study explores the use of curcumin-laponite nanoparticles as carrier vehicles for controlled delivery to in vitro model membranes. Utilizing advanced techniques such as neutron reflectometry, atomic force microscopy, quartz crystal microbalance with dissipation, and infrared spectroscopy, the interaction between curcumin-laponite nanoparticles and solid-supported lipid bilayers is monitored, revealing enhanced stability and controlled release of curcumin across the membrane. These findings pave the way for the development of curcumin-based therapies targeting cardiovascular, neurological, and oncological diseases, leveraging the synergistic effects of curcumin's biological activity and laponite's delivery capabilities.

A preformulation study of marine alkaloid aaptamine: Physicochemical properties investigation and liposomal formulation development toward hepatocellular carcinoma treatment

AbstractHepatocellular carcinoma (HCC) is a global health concern with high prevalence and mortality. A marine alkaloid, AP‐427, has been reported to show potential for HCC treatment. However, its use is limited by low solubility and high toxicity. We aimed to investigate the preformulation parameters and develop AP‐427 liposomes to improve its clinical suitability. A stability‐indicating HPLC assay was established, and the physicochemical properties of AP‐427 were analyzed. Afterward, AP‐427 liposomes were prepared and characterized, and their cytotoxicity was evaluated. AP‐427 had a low solubility at physiological pH, a LogD of 2.56 ± 0.03, and a basic pKa of 3.24 ± 0.12. An entrapment efficiency of 52.71 ± 3.2% was achieved after optimization. The resulting AP‐427 liposomes were 147.2 ± 3.4 nm and stable up to three months when stored in a pellet form at 4°C. The crystallization of AP‐427 in liposomes became less ordered, and AP‐427 liposomes exhibited a controlled release fitted in Korsmeyer–Peppas model, indicating the release was driven by diffusion. Furthermore, AP‐427 liposomes showed a 3.6 times reduced cytotoxicity against HepG2 cells compared with free AP‐427, potentially enhancing its antitumor efficacy. In conclusion, the precise preformulation parameters advanced the AP‐427 liposomal formulation development, which showed potential for HCC treatment.Practical Applications: The aaptamine derivative AP‐427 has shown cytotoxic effects against hepatocellular carcinoma. However, the low solubility and high toxicity limit its clinical application. The present study aims to prepare liposomal formulation to solve the current problems. Results obtained from this study shed light on challenges related to drug solubility and have paved the way for the development of an effective AP‐427 liposomal formulation with promising application in hepatocellular carcinoma therapy.

Application of polyethylene glycol 8000 as plasticizer for the development of ellagic acid and Eudragit® EPO based solid dispersions using hot melt extrusion.

Solid dispersion formation by Hot melt extrusion (HME) is a widely used formulation strategy to improve the solubility and bioavailability of poorly water-soluble drugs. Despite this, they are limited by various factors such as drug-excipient miscibility, poor stability, limited drug loading and extrudability of physical drug-excipient mixtures. In this work, polyethylene glycol 8000 (PEG 8000) was used as a plasticizer for the manufacture of ellagic acid solid dispersions (EASD) with high drug loading. Indeed, EA is a polyphenolic active compound with antimalarial and other promising therapeutic activities. However, its low solubility and low permeability limit its therapeutic use. Solid dispersions formation may overcome this challenge, but its high melting point negatively influences the extrudability of its binary physical mixtures with a high drug loading rate, hence the need to use a plasticizer. Thus, five formulations consisting of EA, Eudragit® EPO and PEG 8000 in the ratio of 15:75:10 (F1), 20:70:10 (F2), 25:65:10 (F3), 15:80:5 (F4) and 20:85:5 (F5) % w/w, respectively, have been extruded, four of which were successful. The extrudates were evaluated by X-ray powder diffraction, FTIR spectroscopy and in vitro dissolution tests. Based on the results of these tests, the F5 formulation was identified as the most promising. Indeed, after 15 min of dissolution test, the dissolution rate of ellagic acid from the formulations was 62.67±3.10%, 58.74±7.23 %, 88.75±3.02% and 83.47±4.40% respectively for formulation F1, F2, F4 and F5. Moreover, the results of the FTIR spectroscopy analyses showed stronger interactions between the different constituents in the F4 and 5 formulations compared to the F1 and 2 formulations. Extruded materials of the F5 formulation, characterized by solid state nuclear magnetic resonance (ssNMR) spectroscopy and subjected to stability studies, showed good physical stability for twelve months under real-time stability study conditions and for six months under accelerated conditions.

Cocrystal Prediction of Nifedipine Based on the Graph Neural Network and Molecular Electrostatic Potential Surface.

Nifedipine (NIF) is a dihydropyridine calcium channel blocker primarily used to treat conditions such as hypertension and angina. However, its low solubility and low bioavailability limit its effectiveness in clinical practice. Here, we developed a cocrystal prediction model based on Graph Neural Networks (CocrystalGNN) for the screening of cocrystals with NIF. And scoring 50 coformers using CocrystalGNN. To validate the reliability of the model, we used another prediction method, Molecular Electrostatic Potential Surface (MEPS), to verify the prediction results. Subsequently, we performed a second validation using experiments. The results indicate that our model achieved high performance. Ultimately, cocrystals of NIF were successfully obtained and all cocrystals exhibited better solubility and dissolution characteristics compared to the parent drug. This study lays a solid foundation for combining virtual prediction with experimental screening to discover novel water-insoluble drug cocrystals.

Investigation of temperature and H2 on GePb/Ge multiple quantum well growth

To reveal the growth behavior of GePb/Ge multiple quantum well (MQW) samples, both the influence of growth temperature and H2/Ar atmosphere are investigated by sputtering epitaxy. As the growth temperature increases from 250 °C to 400 °C, Pb atoms become more active and migrate easily to the surface, forming Pb clusters. As a result, the Pb composition in the GePb/Ge MQW is decreased from 3.5% to 1.8%. When H2 is introduced into the chamber, it is found that the MQW disappears and GePb film with uniform Pb distribution is formed. This is possibly because that the introduction of H2 can retain Pb atoms and the GePb is still grown even if the Pb flux is off. The results show that low temperature and H2 atmosphere are effective methods to further break the low solid solubility limit of Pb in Ge.

An alkaline S/Fe redox flow battery endowed with high volumetric-capacity and long cycle-life

The S/Fe redox flow battery (RFB) with abundant sulfide and iron as redox-active species shows promising applications for energy storage. It exhibits advantages including low cost, high safety, and flexible operation. However, limited by the low solubility limit of [Fe(CN)6]4-, the volumetric capacity of reported S/Fe RFBs is too low to meet commercial requirements. Herein, an alkaline S/Fe RFB with high volumetric energy density and improved cycling stability enabled by the diverse-ion effect in the catholyte is successfully demonstrated. In a 0.50 M KOH solution, the concentration of [Fe(CN)6]4- achieves 1.52 M under ambient temperature which is increased by two times than the solubility limit of K4[Fe(CN)6] (0.76 M) in deionized water. The corresponding theoretical volumetric capacity can reach as high as 40.74 Ah L−1. With 1.30 M [Fe(CN)6]4-in the catholyte, the alkaline S/Fe RFB displays high performance, including a long cycle-life of 3153 h (over 4 months), high Coulombic efficiency (CE) above 99 %, and slow capacity decay of only 0.0166 % per cycle (0.1134 % per day). In addition, at higher temperatures and larger scales, the concentrated catholyte maintains excellent cycling performance, verifying the present strategy is highly reliable in improving the performance of a cost-effective S/Fe RFB system for practical applications.

Development, characterization and Caco-2 cells absorption of curcumin solid dispersion for oral administration

Curcumin is an active dietary compound. However, its low solubility and rapid metabolism limit its absorption in the gastrointestinal (GI) tract and reduces its systemic bioavailability. To overcome these drawbacks, curcumin solid dispersion (CSD) was developed employing polyvinylpyrrolidone (PVP) as a carrier without and with soybean phospholipids (SP) as a co-carrier and prepared using a melting solvent method. The influence PVP and SP on physicochemical properties and in vitro permeability of CSD was investigated. Curcumin in all developed CSD demonstrated amorphous state as confirmed by X-ray diffraction. Spherical particles of ∼140 nm and ∼190 nm were obtained when CSD without and with SP was diluted with water. Consequently, CSD without and with SP possessed significantly greater curcumin water solubility of ∼4200-fold and ∼6500-fold, respectively, as compared to free curcumin, which leading to enhanced curcumin absorption across Caco-2 cell. The dissolution studies, both in 0.1 N HCl and phosphate buffer pH6.8, of CSD showed that curcumin was quickly and completely dissolved within 5 min. Caco-2 cell permeation studies revealed that CSD with SP presented a lag time with slightly lower curcumin absorption than CSD without SP. Moreover, the physical and chemical stability of CSD was found to be stable for up to 6 months at 4 °C and room temperature. From these findings, CSD could be beneficial for enhancing the oral absorption profiles of curcumin.

Curcumin-based nanoformulations alleviate wounds and related disorders: A comprehensive review.

Despite numerous advantages, curcumin's (CUR) low solubility and low bioavailability limit its employment as a free drug. CUR-incorporated nanoformulation enhances the bioavailability and angiogenesis, collagen deposition, fibroblast proliferation, reepithelization, collagen synthesis, neovascularization, and granulation tissue formation in different wounds. Designing nanoformulations with controlled-release properties ensure the presence of CUR in the defective area during treatment. Different nanoformulations encompassing nanofibers, nanoparticles (NPs), nanospray, nanoemulsion, nanosuspension, nanoliposome, nanovesicle, and nanomicelle were described in the present study comprehensively. Moreover, for some other systems which contain nano-CUR or CUR nanoformulations, including some nanofibers, films, composites, scaffolds, gel, and hydrogels seems the CUR-loaded NPs incorporation has better control of the sustained release, and thereby, the presence of CUR until the final stages of wound healing is more possible. Incorporating CUR-loaded chitosan NPs into nanofiber increased the release time, while 80% of CUR was released during 240 h (10 days). Therefore, this system can guarantee the presence of CUR during the entire healing period. Furthermore, porous structures such as sponges, aerogels, some hydrogels, and scaffolds disclosed promising performance. These architectures with interconnected pores can mimic the native extracellular matrix, thereby facilitating attachment and infiltration of cells at the wound site, besides maintaining a free flow of nutrients and oxygen within the three-dimensional structure essential for rapid and proper wound healing, as well as enhancing mechanical strength.

Synthesis and Characterization of Quercetin-Iron Complex Nanoparticles for Overcoming Drug Resistance.

Quercetin, one of the major natural flavonoids, has demonstrated great pharmacological potential as an antioxidant and in overcoming drug resistance. However, its low aqueous solubility and poor stability limit its potential applications. Previous studies suggest that the formation of quercetin-metal complexes could increase quercetin stability and biological activity. In this paper, we systematically investigated the formation of quercetin-iron complex nanoparticles by varying the ligand-to-metal ratios with the goal of increasing the aqueous solubility and stability of quercetin. It was found that quercetin-iron complex nanoparticles could be reproducibly synthesized with several ligand-to-iron ratios at room temperature. The UV-Vis spectra of the nanoparticles indicated that nanoparticle formation greatly increased the stability and solubility of quercetin. Compared to free quercetin, the quercetin-iron complex nanoparticles exhibited enhanced antioxidant activities and elongated effects. Our preliminary cellular evaluation suggests that these nanoparticles had minimal cytotoxicity and could effectively block the efflux pump of cells, indicating their potential for cancer treatment.

Celastrol-encapsulated microspheres prepared by microfluidic electrospray for alleviating inflammatory pain

Inflammatory pain is induced by trauma, infection, chemical stimulation, etc. It causes severe physical and psychological agony to patients. Celastrol has powerful anti-inflammatory property and has achieved good results in various inflammation-related diseases. However, the low water solubility and multi-system toxicity limit its clinical application. Herein, we proposed alginate microspheres with core-shell structure which encapsulated celastrol by microfluidic electrospray to effectively overcome the shortcomings and improve the therapeutic effect. The microspheres had uniform size and good biocompatibility, and could release the loaded drugs in the gut. The behavioral tests showed that the celastrol-loaded microspheres effectively alleviated inflammatory pain, and the hematoxylin and eosin staining (HE staining), immunofluorescence and detection of inflammatory cytokines showed the anti-inflammatory effect. These results indicated that the microspheres could reduce dose and toxicity without affecting efficacy, and facilitate the application of celastrol in different clinical situations.

Multifunctional Nano-Realgar Hydrogel for Enhanced Glioblastoma Synergistic Chemotherapy and Radiotherapy: A New Paradigm of an Old Drug.

Realgar, as a kind of traditional mineral Chinese medicine, can inhibit multiple solid tumor growth and serve as an adjuvant drug in cancer therapy. However, the extremely low solubility and poor body absorptive capacity limit its application in clinical medicine. To overcome this therapeutic hurdle, realgar can here be fabricated into a nano-realgar hydrogel with enhanced chemotherapy and radiotherapy (RT) ability. Our objective is to evaluate the superior biocompatibility and anti-tumor activity of nano-realgar hydrogel. We have successfully synthesized nano-realgar quantum dots (QDs) coupling with 6-AN molecules (NRA QDs) and further encapsulated with a pH-sensitive dextran hydrogel carrier with hyaluronic acid coating (DEX-HA gel) to promote bioavailability, eventually forming a multifunctional nano-realgar hydrogel (NRA@DH Gel). To better investigate the tumor therapy efficiency of the NRA@DH Gel, we have established the mice in situ bearing GL261 brain glioblastoma as animal models assigned to receive intratumor injection of NRA@DH Gel. The designed NRA@DH Gel as an antitumor drug can not only exert the prominent chemotherapy effect but also as a "sustainable reactive oxygen species (ROS) generator" can inhibit in the pentose phosphate pathway (PPP) metabolism and reduce the production of nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting the conversion of glutathione disulfide (GSSG) to glutathione (GSH), reducing GSH concentrations in tumor cells, triggering the accumulation of ROS, and finally enhancing the effectiveness of RT. Through the synergistic effect of chemotherapy and RT, NRA@DH Gel effectively inhibited the proliferation and migration of tumor cells, suppressed tumor growth, improved motor coordination, and prolonged survival in tumor-bearing mice. Our work aims to improve the NRA@DH Gel-mediated synergistic chemotherapy and RT will endow a "promising future" for the old drug in clinically comprehensive applications.

Diffusion in undoped and Cr-doped amorphous UO2

UO2 fuel pellets are often doped with chromium oxide to obtain favourable properties such as higher density, improved thermal stability, large grain sizes, improved pellet-clad interaction margins, and increased fission gas retention during transients. Chromium has a low solubility limit in UO2, with past experimental work reporting solubility limits ranging between 0.004 to 0.06 wt.% Cr. Due to its low solubility, segregation of Cr ions to the grain boundary may occur. Further, the complexity of these boundaries may be high as observed in other ceramics resulting in disordered or amorphous regions along the boundary, affecting a range of material and operational properties of the fuel pellet. To assess these disordered regions, in this work we study amorphous undoped and Cr doped UO2 systems (containing 10–50 at.% Cr3+) that have been modelled using classical molecular dynamics methods incorporating Cr3+ into the well-used CRG potential library. Diffusion coefficients, pre-exponential factors, and activation energies for diffusion were computed for oxygen ions, assessing the impact of structure and extrinsic species on migration. Oxygen diffusion was observed to be much faster in the undoped amorphous system compared to its crystalline counterpart. Oxygen diffusion in doped systems decreased with increasing Cr concentration, highlighting the importance of additives to retain fission products and other migratory species.

Different Curcumin-Loaded Delivery Systems for Wound Healing Applications: A Comprehensive Review

Curcumin or turmeric is the active constituent of Curcuma longa L. It has marvelous medicinal applications in many diseases. When the skin integrity is compromised due to either acute or chronic wounds, the body initiates several steps leading to tissue healing and skin barrier function restoration. Curcumin has very strong antibacterial and antifungal activities with powerful wound healing ability owing to its antioxidant activity. Nevertheless, its poor oral bioavailability, low water solubility and rapid metabolism limit its medical use. Tailoring suitable drug delivery systems for carrying curcumin improves its pharmaceutical and pharmacological effects. This review summarizes the most recent reported curcumin-loaded delivery systems for wound healing purposes, chiefly hydrogels, films, wafers, and sponges. In addition, curcumin nanoformulations such as nanohydrogels, nanoparticles and nanofibers are also presented, which offer better solubility, bioavailability, and sustained release to augment curcumin wound healing effects through stimulating the different healing phases by the aid of the small carrier.

Enhanced triclosan biodegradation by a biphasic bioreactor

Triclosan (TCS), an antiseptic agent that facilitates the formation of microbial resistances, has been widely used and is therefore ubiquitously detectable in wastewater. However, structure and low water solubility limit both microbial transformation kinetic and removal efficiency of TCS. Therefore, the use of solubilizers or non-aqueous phases (NAP) appears to be a suitable approach for rapid, complete, and cost-effective treatment of highly contaminated TCS point sources such as sports clubs, hospitals, industrial wastewater treatment plants or synthesis effluents without dilution effects.The mixed culture TCSmix100 previously isolated and characterized, and able to completely mineralize TCS at stoichiometric chloride release, was investigated in presence or absence of solubilizers in lab-scale well stirred batch reactors. While TCS conversion was limited in solubilizer-free tests due to limited solubility of TCS crystals within the aqueous phase, solubilizers enhanced water solubility, mass transport and microbial kinetics. Thus, TCS transformation rate at initial 1.45 g TCS L−1 was further increased from a high level of 155–172 mg L−1d−1 without solubilizers to 399 mg L−1d−1 or to 888 mg L−1 d-1 providing β-pinene or α-pinene as NAPs, i.e., by a factor of 2.3–5.2, exceeding kinetic parameters of other strains described in literature by at least two orders of magnitude. These results clearly demonstrate the high TCS mineralization capacity of this biphasic treatment technologies and its applicability in treatment of highly contaminated TCS point-sources to eliminate recalcitrant contaminants at high levels before getting diluted.

The Effect of Holding Time on Dissimilar Transient Liquid-Phase-Bonded Properties of Super-Ferritic Stainless Steel 446 to Martensitic Stainless Steel 410 Using a Nickel-Based Interlayer.

The dissimilar joining of martensitic and ferritic stainless steels have been developed that needs corrosion resistance and enhanced mechanical properties. In this study, the transient liquid-phase bonding of martensitic stainless steel 410 and super-ferritic stainless steel 446 was conducted with a nickel-based amorphous interlayer (BNi-2) at constant temperature (1050 °C) and increasing times of 1, 15, 30, 45, and 60 min. For characterization of the TLP-bonded samples, optical microscopy and scanning emission microscopy equipped with energy-dispersive X-ray spectroscopy were used. To investigate the mechanical properties of TLP-bonded samples, the shear strength test method was used. Finally, the X-ray diffraction method was used for microstructural investigation and phase identification. The microstructural study showed that the microstructure of base metals changed: the martensitic structure transited to tempered martensite, including ferrite + cementite colonies, and the delta phase in super-ferritic stainless steel dissolved in the matrix. During the transient liquid-phase bonding, the aggregation of boron due to its diffusion to base metals resulted in the precipitation of a secondary phase, including iron-chromium-rich borides with blocky and needle-like morphologies at the interface of the molten interlayer and base metals. On the other hand, the segregation of boron in the bonding zone resulted from a low solubility limit, and the distribution coefficient has induced some destructive and brittle phases, such as nickel-rich (Ni3B) and chromium-rich boride (CrB/Cr2B). By increasing the time, significant amounts of boron have been diffused to a base metal, and diffusion-induced isothermal solidification has happened, such that the isothermal solidification of the assembly has been completed under the 1050 °C/60 min condition. The distribution of the hardness profile is relatively uniform at the bonding zone after completing isothermal solidification, except the diffusion-affected zone, which has a higher hardness. The shear strength test showed that increasing the holding time was effective in achieving the strength near the base metals such that the maximum shear strength of about 472 MPa was achieved.

Supramolecular Design Strategy of a Water-Soluble Diphenylguanidine-Cyclodextrin Polymer Inclusion Complex.

Diphenylguanidine (DPG) is a widely used secondary accelerator for the vulcanization of natural rubber (NR) latex. However, its low water solubility and high toxicity limit its use in high-end NR products. In this study, a water-soluble inclusion complex of DPG and a β-cyclodextrin polymer (β-CDP), termed DPG-β-CDP, was prepared through supramolecular interactions and characterized using Fourier-transform infrared spectroscopy, 1H NMR, scanning electron microscopy, and UV-vis spectroscopy techniques. In comparison with that of DPG, the water solubility of DPG-β-CDP was greatly enhanced because of the water-soluble host molecule. The molar ratio of DPG to the CD unit in β-CDP was determined to be 1:1. At 25 °C, the binding constant of DPG-β-CDP was found to be 9.2 × 105 L/mol by UV-vis spectroscopy. The proposed method for forming inclusion complexes with high potential for use as water-soluble vulcanization accelerators is promising.

Preparation of polydopamine-modified celastrol nanosuspension and its anti-liver cancer activity in vitro

Celastrol (CEL) is one of the main effective components of traditional Chinese medicine Tripterygium wilfordii Hook.f, which has high antitumor activity. However, its low solubility and low bioavailability limit its clinical use. In this study, a CEL nanosuspension (PDA@CEL-NS) with near-infrared photothermal properties was prepared. PDA@CEL-NS contained spherical nanoparticles with an average particle size of 189.67 nm, zeta potential of −30.23 mV, and 60.33% drug loading. X-ray diffraction showed that PDA@CEL-NS had an amorphous structure. PDA@CEL-NS had good stability after storage at 4 °C and 37 °C for 30 days, and there was no aggregation or sedimentation in a 5% glucose solution or culture medium. The highly dispersed nanoparticles greatly improved dissolution in vitro, and the cumulative release rate of PDA@CEL-NS over 72 h was as high as 60.10%. It demonstrated both high release and a good sustained-release effect. Cell experiments showed that PDA@CEL-NS had stronger efficacy than CEL-NS or CEL, and the efficacy was further enhanced after laser application. Nuclear rupture and deformation and the induction of apoptosis were potential toxic mechanisms, and they also inhibited cell migration. In conclusion, PDA@CEL-NS is expected to become a nano-drug delivery system for the treatment of cancer.

Preparation, Physicochemical Characterization, and Antioxidant Activity of Naringin-Silk Fibroin-Alginate Microspheres and Application in Yogurt.

Naringin is the major polyphenol in bitter orange peel with antioxidant property. However, its pH sensitivity, low solubility, and bitter taste limit its application in food. In this study, naringin–sodium alginate–silk fibroin microspheres were prepared by the ionic gel method. The loading capacity and encapsulation efficiency of naringin in microspheres were 13.2% and 77.6%, respectively. The morphology of microspheres was characterized by scanning electron microscopy. The X-ray diffractometry and differential scanning calorimetry results showed naringin was amorphous after encapsulation. Fourier-transform infrared spectroscopy and molecular docking analysis confirmed the intermolecular hydrogen bonds between naringin and sodium alginate. Naringin could release from the microspheres continuously under different pH conditions. Compared with free naringin, the 2,2-diphenyl-1-picrylhydrazyl scavenging activity and the stability of naringin microspheres were significantly improved. The application of naringin microspheres in yogurt indicated the precipitation of whey could be effectively reduced and the decline rate of pH was inhibited. The study suggested that naringin encapsulated microspheres were beneficial for improving the shelf life of this bioactive product as well as providing a new idea for functional yogurt.

Phospholipid-Based Microemulsions for Cutaneous Imiquimod Delivery.

Imiquimod (IMQ) is a potent immune response modifier with antiviral and antitumor properties. IMQ’s low aqueous solubility and unsatisfactory cutaneous permeability limit its formulation into effective dosage forms. This work aimed to develop IMQ-loaded microemulsions (MEs) based on phospholipids and oleic acid to improve IMQ penetration into the epidermis. A pseudo-ternary phase diagram was constructed, and the microstructure of the formulations was examined by measuring the conductivity values. Selected MEs were characterized and studied for their ability to deliver IMQ into and through ex vivo human skin. ME1 with 1% IMQ (bicontinuous ME with Bingham rheology) delivered similar IMQ quantities to the human epidermis ex vivo as the commercial product while having a 5-fold lower IMQ dose. IMQ was not detected in the acceptor phase after the permeation experiment, suggesting a lower systemic absorption risk than the established product. Infrared spectroscopy of the stratum corneum revealed less ordered and less tightly packed lipids after ME1 application. The ME1-induced barrier disruption recovered within less than 5 h after the formulation removal, as detected by transepidermal water loss measurements. In conclusion, our findings demonstrate that phospholipid and oleic acid-based MEs could become a promising alternative for topical IMQ administration.