High-pressure Homogenization Research Articles

Fenofibrate Nanosuspension: A Novel Strategy to Enhance its Bioavailability for the Management of Hyperlipidemia

Hyperlipidemia, a metabolic condition marked by elevated plasma levels of cholesterol or triglyceride-carrying lipoproteins, is a major contributor to atherosclerosis and cardiovascular diseases. Antihyperlipidemic drugs are classified according to their primary mechanism of action. Fenofibrate’s role in regulating cholesterol and managing insulin resistance-associated metabolic disorders makes it a preferred choice in combination therapies with statins for cardiovascular disease management. Nanoparticles have gained attention for enhancing the bioavailability of poorly water-soluble drugs by reducing particle size to the nanoscale (100-200 nm), which increases solubility, dissolution rate and adhesion to cell surfaces. Nanosuspensions improve drug solubility and bioavailability through methods like media milling, high-pressure homogenization and precipitation. Despite advancements, producing stable Fenofibrate nanoparticles below 100 nm at an industrial scale remains a challenge. Recent strategies include using sonication and freeze-drying to enhance bioavailability and solubility, achieving significant improvements in drug dissolution and therapeutic efficacy.

Enhancing exemestane delivery: Solid lipid nanoparticles formulation and pharmacokinetic evaluation

This research investigates the development of exemestane (EXM) solid lipid nanoparticles (SLNs) for the purpose of improving drug delivery. To prepare EXM SLNs, glycerol monostearate was used as the lipid and Tween 80 as the surfactant and solvent injection followed by high-pressure homogenization as a method of preparation. The formulation parameters were optimized, leading to the development of a promising formula. The formula has a particle size of 188.72 ± 5.62 nm, a polydispersity index (PDI) of 0.215 ± 0.023, and an %EE of 65.39 ± 2.54 %. The formulation's robustness was indicated by minimal changes in particle size and %EE over 30 days, as revealed by stability studies. The bioavailability of EXM SLNs was found to be significantly improved in Wistar rats compared to conventional EXM suspension, as shown by pharmacokinetic studies. The formula that was optimized showed a higher maximum plasma concentration (Cmax) of 168.92 ± 2.40 ng/mL, a delayed time to reach Cmax (Tmax) of 4 hours, and significantly higher area under the curve (AUC) values. These results highlight the effectiveness of the optimized formula in improving drug absorption and bioavailability. The findings indicate that EXM SLNs show potential for enhancing the delivery and effectiveness of EXM, specifically in the treatment of breast cancer.

Cell Disruption and Hydrolysis of Microchloropsis salina Biomass as a Feedstock for Fermentation

Microalgae are a promising biomass source because of their capability to fixate CO2 very efficiently. In this study, the potential of Microchloropsis salina biomass as a feedstock for fermentation was explored, focusing on biomass hydrolysis by employing various mechanical and chemical cell disruption strategies in combination with enzymatic hydrolysis. Among the mechanical cell disruption methods investigated on a lab scale, namely ultrasonication, bead milling, and high-pressure homogenization, the most effective was bead milling using stainless-steel beads with a diameter of 2 mm. In this way, 87–97% of the cells were disrupted in 40 min using a mixer mill. High-pressure homogenization was also effective, achieving 86% disruption efficiency after four passes on a 30–200 L scale using biomass with 15% (w/w) solids content. Enzymatic hydrolysis of the disrupted cells using a mixture of cellulases and mannanases yielded up to 25% saccharification efficiency after 72 h. Acidic hydrolysis of undisrupted cells followed by enzymatic treatment yielded around 30% saccharification efficiency but was coupled with significant dilution of the resulting hydrolysate. Microalgal biomass hydrolysate produced was determined to have ~8.1 g L−1 sugars and 2.5% (w/w) total carbon, as well as sufficient nitrogen and phosphorus content as a fermentation medium.

Effect of Litsea cubeba and Cinnamon Essential Oil Nanoemulsion Coatings on the Preservation of Plant-Based Meat Analogs

Plant-based meat analogs (PBMAs) are promising sustainable food sources. However, their high moisture and protein contents make them prone to microbial deterioration, limiting their shelf life and sensory appeal. This study explored enhancing PBMAs’ shelf life using nanoemulsions of Litsea cubeba and cinnamon essential oils, emulsified with chitosan and Tween 80. The composite nanoemulsion, produced through high-pressure homogenization, exhibited a droplet size of 4.99 ± 0.03 nm, a polydispersity index (PDI) of 0.221 ± 0.008, and a zeta potential of 95.13 ± 2.67 mV, indicating remarkable stability (p < 0.05). Applied to PBMAs stored at 4 °C, it significantly improved color and pH balance and reduced thiobarbituric acid reactive substances and cooking loss. Most notably, it inhibited the growth of Escherichia coli and Staphylococcus aureus, curbing spoilage and protein oxidation, thereby extending the products’ shelf life and preserving sensory quality. As shown above, the encapsulation of LCEO/CEO in nanoemulsions effectively inhibits spoilage and deterioration in PBMAs, improving flavor and quality more than direct addition. Future studies should explore using various essential oils and emulsifiers, as well as alternative encapsulation techniques like microcapsules and nanoparticles, to further prevent PBMA deterioration.

Protective Effects of Carotenoid-Loaded Nanostructured Lipid Carriers Against Ochratoxin-A-Induced Cytotoxicity

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceous and various Penicillium species, which are known for contaminating agricultural products and posing significant health risks, which include immunotoxicity. This study aims to evaluate the potential of nanostructured lipid carriers (NLCs) loaded with a carotenoid-enriched extract from pumpkin peel (Cucurbita maxima L.) in mitigating the toxic effects of OTA. To address the poor bioavailability and instability of carotenoids, nanoencapsulation techniques were employed to enhance their delivery and efficacy. NLCs were formulated using hydrogenated sunflower oil, pumpkin oil, and soy lecithin using hot high-pressure homogenization. The in vitro study involved co-digesting OTA-contaminated bread with an NLC formulation and assessing the impact of the encapsulated carotenoid on OTA bioaccessibility, bioavailability, and cellular toxicity using Caco-2 and Jurkat T cells. Even though no significant influence was observed on the bioaccessibility and bioavailability of OTA, carotenoid-loaded NLCs exhibited cytoprotective effects by improving cell viability and mitigating OTA-induced toxicity in both Caco-2 and Jurkat T cells. Particularly, the flow cytometry analysis highlighted the ability of carotenoids to mitigate OTA-induced cellular damage by decreasing ROS production and limiting mitochondrial mass changes. The study suggests that the encapsulation of carotenoids in NLCs represents a promising strategy to enhance their protective effects against OTA toxicity, potentially offering a novel approach to food safety and public health protection. The study underscores the potential of nanotechnology in improving the bioavailability and efficacy of natural antioxidants to mitigate mycotoxin-induced damage.

Optimization of the Homogenization Process of Ginseng Superfine Powder to Improve Its Powder Characteristics and Bioavailability.

As consumer demands evolve for health supplements, traditional ginseng products are facing challenges in enhancing their powder characteristics and bioavailability. The objective of this study was to prepare a novel ginseng superfine powder using a high-pressure homogenization (HPH) process. Response surface methodology was employed to determine the effects of HPH parameters (pressure, number of passes, and concentration) on particle size and the dissolution of the saponin components of the superfine powders. The Box-Behnken design of experiments was applied to ascertain the optimal HPH parameters for the smallest particle size and the highest dissolution of the saponin components. For the powders obtained at different parameters, the characterization of tap density, bulk density, flowability, water-holding capacity, appearance, and taste were observed. The optimized experimental conditions for the HPH process were as follows: 15,000 psi (pressure), 3 (number of passes), and 1 kg/L (concentration). The optimized values were 55 μm (particle size) and 83 mg/g (dissolution of the saponin components), respectively. The method offered technical support for the application of the HPH process in the preparation of ginseng powders. The objects of this research could be broadened to include a diverse array of botanical materials, addressing contemporary demands for cost-effectiveness and sustainability within the industry.

Hemp cellulose-based aerogels and cryogels: From waste biomass to sustainable absorbent pads for food preservation

This study presents a circular economy approach utilizing hemp stems and rice straw, typically perceived as low-value agricultural waste, to develop a sustainable alternative to traditional plastic absorbent pads for food packaging. The development of an active material was achieved through the utilization of hemp cellulose and a bioactive extract isolated from rice straw. In addition to reducing plastic pollution, this material demonstrates the potential to enhance food preservation. This research provides evidence of the benefits of repurposing agricultural by-products to create valuable and environmentally-friendly products. Hemp cellulose was extracted, characterized, and processed to develop stable aerogels and cryogels through supercritical CO2 drying and freeze-drying. The water stability and internal structure of the materials were guided via TEMPO-mediated oxidation and high-pressure homogenization. Both materials showed versatile physicochemical and mechanical properties. Nevertheless, with higher water sorption (2.20 mL/g), minimal dimensional changes, and lower shrinkage, cryogels were suitable for meat absorbent pad application. To enhance the cryogels functionality, they were impregnated with a rice straw bioactive extract in two different concentrations. The incorporation of the extract did not affect the structure of the cryogels, improved their mechanical properties and the antioxidant activity remained stable after drying (63.89–78.96 %). Finally, the performance of the developed materials was compared to commercial plastic pads and pristine meat preservation challenge test during 9 days at refrigeration conditions. The incorporation of rice straw extract improved meat color preservation. While moderate extract concentrations (75 mg/g) showed a protective effect against lipid oxidation, higher levels (187.5 mg/g) induced pro-oxidant reactions. This research highlights the potential of hemp cellulose-based cryogels as sustainable and functional packaging materials for meat products.

Impact of Various Extraction Technologies on Protein and Chlorophyll Yield from Stinging Nettle.

Stinging nettle (Urtica dioica L.) has gained attention as a sustainable protein source due to its rich bioactive compound profile and medicinal properties, but research on optimizing its protein extraction remains limited. This research explores various cell disruption methods, including pulsed electric fields and high-pressure homogenization, combined with extraction techniques like isoelectric precipitation, ultrafiltration, and salting-out, to enhance protein yield and assess its impact on chlorophyll content. The findings indicate that high-pressure homogenization combined with isoelectric precipitation achieved the highest protein yield of 11.60%, while pulsed electric fields with ultrafiltration significantly reduced chlorophyll content from 4781.41 µg/g in raw leaves to 15.07 µg/g in the processed sample. Additionally, the findings suggest that innovative extraction technologies can improve the efficiency and sustainability of protein isolation from stinging nettle, offering a valuable addition to the repertoire of alternative protein sources. These advancements could pave the way for broader applications of stinging nettle in food fortification and functional ingredient development.

Cubosomes – A novel approach to taste masking using ibuprofen as a model drug

Taste masking of any pediatric oral formulation has always been a hurdle. Cubosomses, a type of lyotropic liquid crystal, have been used in this research to develop an oral formulation of ibuprofen. Ibuprofen cubosomes were prepared with glyceryl monooleate (GMO) and poloxamer 407 by high-pressure homogenization (HPH) technique. The formulation experiments were performed using a 2-level, 3-factor central composite design with drug loading, GMO concentration and HPH pressure as independent variables and vesicle size, entrapment efficiency and %drug content as the dependent variables. The most suitable ibuprofen cubosomes showed 94 nm vesicle size, −17.5 mV zeta potential, >75% drug content and >96% entrapment efficiency. The cubosomes released more than 80% of the drug within 2 hours. In vitro taste masking study showed significantly lower drug release than its bitterness threshold. An in vivo taste masking study in healthy adult volunteers showed significant taste masking compared to the marketed formulation and ibuprofen pure suspension. % of the volunteers observed cubosomes as not bitter. In contrast, 67% of the volunteers reported marketed suspension as very bitter. The developed cubosomes resulted in physical stability for three months of proper storage. The study has successfully achieved considerable taste-masking using cubosomes with GMO and Poloxmaer 407 formulation. This proof of concept can initiate a new field of research in taste-masked oral liquid formulation.

Ultra-high-pressure homogenization in chicory root juice production

The demand for freshly squeezed natural fruit juices has increased in recent years, however their shelf life is quite short. Thermal processes applied to extend the shelf life of such products and increase their storage stability cause significant losses in color and other sensory properties, depending on the temperature applied. Therefore, the preference for high-pressure homogenization as an alternative to thermal processes is on the rise. We aimed to determine effects of ultra-high-pressure homogenization and production stages on some quality properties of chicory root juice. Ultra-high-pressure homogenization was applied at the pressure levels of 0 (Control), 50, 100, 150, and 200 MPA. The samples also included juice after homogenization with an ULTRA-TURRAX disperser and after a water bath. Ultra-high-pressure homogenization affected such quality characteristics of chicory root juice as total soluble solids (p < 0.01), pH (p < 0.01), L* (p < 0.01), a* (p < 0.01), b* (p < 0.01), a*/b* (p < 0.01), chroma (p < 0.01), hue angle (p < 0.01), and total color difference ΔE (p < 0.01). Higher levels of ultra-high-pressure homogenization pressure increased pH (p < 0.05), a* values (p < 0.05), and the a/b* ratio (p < 0.05) but reduced L* (p < 0.05), b* (p < 0.05), chroma (p < 0.05), and hue angle (p < 0.05) values of the juice samples. Thus, the use of ultra-high-pressure homogenization (100 and 200 MPa) contributed to improving the total soluble solids and redness values of chicory root juice. Our study showed that the ultra-high-pressure homogenization process improved the quality of chicory root juice.

Guiding Therapeutics: Lipid Labyrinths and Nanostructures for Enhanced Drug Delivery

Abstract: Nanostructured lipid carriers (NLCs) offer a breakthrough platform for drug therapy, surpassing traditional limitations and delivering exceptional performance. Among various nanoparticulate systems, lipid nanoparticles stand out as one of the most promising options for medication delivery. NLCs stand out due to their solid matrix at ambient temperatures, setting them apart from conventional lipid-based carriers such as nanoemulsions and solid lipid nanoparticles. This paper thoroughly explores the makeup, classification, components, and various methods of preparing NLCs, based on extensive research findings. It emphasizes their numerous advantages, such as improved stability, minimal toxicity, extended storage capability, increased drug-loading capacity, and compatibility with biological systems. The review provides insights into the advantages and limitations of each method. Exploring the intricacies of drug loading and release, the review also addresses strategies to bolster NLCs’ stability. Moreover, it provides a detailed summary of both laboratory- based and animal studies demonstrating the efficacy of NLCs carrying cytotoxic drugs, particularly emphasizing their promise in targeted drug delivery to the brain. As the next-generation lipid nanocarriers, NLCs are composed of physiological and biocompatible lipids, rendering them novel pharmaceutical formulations. These colloidal drug delivery systems boast a solid lipid matrix with nanosized structures, offering superior drug loading capacity, physical stability, and bioavailability compared to conventional lipid nanoparticles. Several techniques, including high-pressure homogenization, microemulsion, solvent evaporation, and melt emulsification, add to the flexibility of nanostructured lipid carriers. Additionally, their exterior can be altered using coatings such as polyethylene glycol, chitosan, or antibodies to improve targeting ability and stealth characteristics. By elucidating the promising role of NLCs across diverse drug delivery systems, this review stimulates interest in their potential applications. It underscores the significance of understanding the structure, content, multiple formulation procedures, and characterization of NLCs, which are pivotal aspects for establishing stable drug delivery systems.

Frabrication of carboxymethylchitin nanofibers and fish gelatin hybrid gels with robust gel performance

Compared to animal gelatin, the application of fish gelatin (FG) in the food industry is limited due to its lower gel hardness, gelation temperature, and melting temperature. To address these issues, we developed hybrid gels using carboxymethyl chitin nanofibers (CMC-NFs) with FG to enhance its gel properties. The chitin was carboxymethylated by monochloroacetic acid, increasing the negative potential from −6 mV to −35 mV. This modified chitin was then defibrillated into CMC-NFs through high-pressure homogenization to improve its water dispersibility. The addition of 0.1% CMC-NFs significantly increased the hardness of FG gels from 533 g to 989 g, which was notably higher than the ∼600 g hardness of porcine gelatin. Additionally, the gelation and melting temperatures of FG reached 17 °C and 32 °C, respectively, which are very close to the 20 °C and 35 °C of porcine gelatin. Mechanistic studies revealed that FG and CMC-NFs (0.1%) molecules formed a synergistic gel network, facilitated by hydrogen bonding and hydrophobic interactions. This interaction significantly increased the α-helix content in the secondary structure of the FG protein from 15.26% to 21.18%, thereby enhancing the FG-dominated three-dimensional network structure with CMC-NF molecules. Increasing the concentration of CMC-NFs further elevated the gel's melting temperature while reducing its hardness due to phase separation. This study not only presents a viable method for enhancing the gelling properties of modified FG but also offers a feasible solution for expanding FG's applications in the food industry.

Bioprocess to produce biostimulants/biofertilizers based on microalgae grown using piggery wastewater as nutrient source

In the present work, two downstream processes − high-pressure homogenization at 100 (HPH-100) and 1200 bar (HPH-1200), and enzymatic hydrolysis (EH) − were tested to produce biostimulant extracts from Tetradesmus obliquus grown in piggery wastewater at two concentrations (12.8 and 88.3 g/L). Extracts before and after centrifugation (C) were evaluated in four bioassays using garden cress (germination), mung bean (auxin-like activity), and cucumber (auxin- and cytokinin-like activity) relative to distilled water. The initial microalgal culture, without any treatment, had the best germination results (162 % at 0.2 g/L) and the only one that showed cytokinin-like activity (141 % at 0.5 g/L). In both auxin-like bioassays, the HPH-1200 + C and EH + C originated high values (186 and 155 % for cucumber, 290 and 285 % for mung bean, respectively). For mung bean, the HPH-1200 achieved the highest auxin-like effect (378 %). Finally, the extracted biomass contained essential nutrients for biofertilization, complementing the biostimulant extracts for sustainable agriculture application.

Freeze-dried wafers containing sesame oil for alleviation of dry mouth

A dry mouth is a condition with significant morbidity. Conventional saliva substitutes are expensive, short-lived, and prone to contamination. This study presents a Freeze-Dried Sesame Oil Emulsion Saliva Substitute (FD-SOESS), which combines the advantages of sesame oil through a freeze-drying process and assesses its effectiveness. High-speed homogenization (HSH) as well as high-pressure homogenization (HPH) techniques were employed to fabricate the FD-SOESS. The formulations that underwent the additional HPH step demonstrated improved physical properties, such as lower viscosity and faster redispersion times, compared to HSH alone. The optimized formulation (F11) possessed a near neutral pH of 6.67 and rapid re-dispersibility that was <141.5 s), which is acceptable for oral administration. Additionally, the FD-SOESS formulation revealed heterogeneous porous structures with a layered arrangement of different pore sizes, and the resulting formulation had low moisture content (2.76 %). The formulation met the microbial limit test. The antioxidant IC₅₀ of sesamin was found to be 0.318 μM. Furthermore, it was not toxic to periodontal cells at 50 μg/mL or 100 μg/mL. Human periodontal cell lines subjected to scratch and treated with FD-SOESS demonstrated notable migration that achieved complete wound closure within two days. The administration of FD-SOESS led to a notable elevation in the mucus concentrations found in the saliva samples of all participants. Overall, the results indicated that FD-SOESS is a highly promising alternative to saliva and may improve oral health for individuals suffering from dry mouth.

Streamlining process development and scale-up: Risk assessment to reduce workload in primary protein recovery

Risk assessment is an integral aspect of the Quality-by-Design strategy to identify potential obstacles at every stage of biopharmaceutical production, from process development to tech transfer. We explored flow process chart, root cause analysis, and failure mode and effects analysis, to assess the scale-up of bacterial cell disruption and its influence on centrifugation and filtration steps. The Ishikawa diagram suggests that data on the impact of homogenizer valve design on product release, impurity profile, particle size distribution, viscosity, and dsDNA fragment size are missing which were collected experimentally for this study. Cell lysates from micro-, lab- and pilot scales cell disruption were analyzed for the above-mentioned parameters. Process parameters affecting these output parameters were identified on each individual scale. Cell disruption on the micro scale was performed in a bead mill. High pressure homogenization was used on lab- and pilot scales. Cell disintegration by bead milling delivers homogenates of product and impurity content comparable to those on bench scale but with 3-fold higher viscosity and significantly larger dsDNA fragments, 8.0 instead of 1.0 kbp, respectively. Miniaturized pressure flow curves identified dsDNA fragment sizes as critical for filter performance during clarification. Combining risk assessment, micro scale cell disintegration and bench scale pressure flow curves allows for selective and efficient process development, and scale up for primary recovery steps.

Optimisation and Characterisation of Improved Nanoemulsion Formulations Containing Ceramide 3

AbstractCeramide3 (Cer3) is one of the important components of stratum corneum (SC) lipids with good moisturizing and repairing properties. However, it suffers from (a) poor solubility, (b) easy crystallization and precipitation, and (c) strong polarity and difficulty in transdermal application. This study aimed to load Cer3 into nanoemulsions (NEs) to overcome these mentioned defects. The optimized NEs formulation was prepared by high pressure homogenization method and characterized by several methods. The optimized ceramide3 nanoemulsions (Cer3‐NEs) exhibited a good physico‐chemical stability over 3 months under different conditions, with droplet size of 103.1 nm, PDI of 0.178, zeta potential of −39.09 mV, pH of 6.20 and encapsulation efficiency of 96.39 %. Turbiscan results showed that formulations containing Cer3‐NEs have better stability than those containing free Cer3. The dermal delivery ability of Cer3‐NEs was assessed by Franz diffusion and confocal Raman spectroscopy (CRM). In vitro and in vivo penetration studies showed that Cer3‐NEs serum have almost 2–3 times higher retention in the skin and permeation in the receptor solution compared to serum with free Cer3. The findings show NE is a promising carrier of Cer3 for topical administration in the treatment of dryness and barrier damage due to higher stability and better skin permeability.

Are Nanostructured Lipid Carriers (NLC) better than Solid Lipid Nanoparticles (SLN) for delivering abiraterone acetate through the gastrointestinal tract?

Abiraterone acetate (AbA) is a progesterone derivative indicated for the treatment of metastatic prostate cancer. This BCS (Biopharmaceutics Classification System) Class IV molecule has an extremely poor oral bioavailability (<10 %), notably due to its very low water solubility and intestinal permeability. Among the few existing galenic strategies to improve AbA’s oral bioavailability, lipid nanoparticles such as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are relevant nanovectors. The objective of this study is to develop and compare SLN and NLC for oral delivery of abiraterone acetate. Both SLN and NLC are biocompatible, biodegradable and produced by high pressure homogenization (HPH), an ecological-friendly manufacturing process, organic solvent-free and easily scalable. The HPH process allowed the formation of AbA-loaded SLN and NLC with particle size lower than 160 nm and high encapsulation efficiencies. The addition of a liquid lipid significantly reduced the mean diameter of the nanoparticles, reflecting the greater benefit of the NLC formulation compared to SLN. Both SLN and NLC formulations offered an important protection of AbA in intestinal media, with a better stability for NLC. When encapsulated in SLN or NLC, the AbA is strongly retained by the nanoparticles, whatever the dissolution medium, which means that both formulas are able to protect and retain the drug in the intestinal tract, right up to its delivery to the enterocytes surface. High concentrations of nanoparticles were administered without cytotoxicity, especially for the NLC, which provides a real added value in terms of biocompatibility with Caco-2 cells. Finally, the nanoparticles were able to penetrate into enterocytes by the transcellular route, demonstrating an intense cellular internalization.

Study on the preparation of stabilizer-free silymarin nanocrystals and its oral absorption mechanisms

Many researchers have studied the oral absorption mechanisms yet, however, considering stabilizers often participate in the absorption process of nanocrystals, these known mechanisms may be incorrect. Hence in this study, we aimed to explore the correct absorption mechanism of nanocrystals by performing related studies on stabilizer-free nanocrystals. We firstly prepared stabilizer-free silymarin nanocrystals by high-pressure homogenization, and then performed absorption-related studies, such as solubility, dissolution rate, pharmacokinetic study, cellular uptake and intracellular transport. Results showed the stabilizer-free silymarin nanocrystals had an average particle size of (450.2 ± 4.46) nm, with PDI of 0.280 ± 0.021 and Zeta potential of −26.9 ± 2.4 mV. The conversion of silymarin crude drug to stabilizer-free silymarin nanocrystals increased the compound's solubility by 1.41 times, with a dissolution rate of 92.2 % in water within 30 min compared to 38.5 % for crude drugs. Pharmacokinetic studies showed the oral bioavailability of stabilizer-free silymarin nanocrystals was found to be 1.48 times greater than that of the crude drugs. The cell experimentation results demonstrated that the stabilizer-silymarin nanocrystals can improve uptake but have poor transmembrane transport properties. Most researchers believe that nanocrystals can enhance transmembrane transport of drugs via an endocytosis-mediated pathway. In fact, nanocrystals are indeed endocytosed more by the cells, but this transport pathway is poor because the cells lack the intracellular transport pathway to transport nanocrystals from the AP side to the BP side. Therefore, we believe that the intracellular transport of nanocrystals can be enhanced by modifications and other carriers if needed to improve nanocrystals' ability to promote oral absorption.

A Novel Etanercept-loaded Nano-emulsion for Targeted Treatment of Inflammatory Arthritis via Draining Lymph Node.

Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune response and inflammatory cytokine production. The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions (NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2. A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were investigated by using a laser particle size analyzer and transmission electron microscopy, respectively. The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation. In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development of the mouse arthritis model. Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA) mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as, anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN. NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work provides an experimental foundation for expanding the clinical application of EN.

Dynamic/static pressure-induced copolymerization and property changes of lotus seed starch with chlorogenic acid

Pressure promotes the formation of starch-polyphenol complexes, but their classification and properties are still unclear. This study aimed to elucidate the effects of dynamic high-pressure homogenization (10–50 MPa) and static hydrostatic pressure (100–500 MPa) on the copolymerization behavior and properties of lotus seed starch (LS)–endogenous polyphenol chlorogenic acid (CA) complexes. The results showed that both pressures induced LS–CA to form stable inclusion-type complexes and easily destructible noninclusion-type complexes. Increased pressure promoted the formation of inclusion-type complexes, with dynamic pressure having a particularly strong effect. However, noninclusion-type complexes began breaking down at 20 MPa under dynamic pressure and 300 MPa under static pressure. Inclusion-type complexes primarily improve starch ordering, and noninclusion-type complexes enhance water holding capacity, but excessive proportions of either type affect pasting performance. These findings offer insights into transforming specific starch structures through small molecular components and provide a theoretical basis for controlling functional starch product processing.