Particle Polydispersity Research Articles

Quercetin-loaded nanoemulsions prevent Scopolamine-induced neurotoxicity in male rats

Quercetin (QCT) is well-known as a neuroprotective agent due to its antioxidant capacities and reinstating mitochondrial functions. Scopolamine is commonly used as a model to induce Alzheimer's disease (AD-like) symptoms. The current study develops QCT-loaded nanoemulsion (QCT-NE) accompanied by evaluating its neuro-therapeutic effectiveness against SCO-induced neurotoxicity in male rats.The QCT-NE was prepared by the spontaneous emulsification technique and characterized by using particle size, zeta potential, drug loading, in vitro drug release behavior, and stability studies. In vivo studies were done on adult Wistar rats by applying the Morris water maze (MWM) test to study spatial memory and learning. The levels of lipid peroxidation and reduced glutathione were quantitatively determined to reveal the potential mechanism of SCO-induced oxidative stress. Finally, histological studies were performed using staining techniques.The QCT-NE particle size, zeta potential, polydispersity index (PDI), and DL were obtained at 172.4 ± 16.8 nm, -29 ± 0.26 mV, 0.3 ± 0.07, and 81.42 ± 9.14 %, respectively. The QCT and more effectively QCT-NE reduced the elevation of neurobehavioral abnormalities in the MWM test in SCO-exposed rats. The results of oxidative status showed that SCO significantly could increase the LPO and decrease the GSH levels in the rat's brain. However, QCT-NE treatment was more effective than free QCT to inhibit oxidative damage and was well correlated with histopathological findings.Taken together, QCT-NE, compared to QCT, was superior in ameliorating SCO-induced AD-like symptoms due to its better neuroprotective activity and can be considered a novel supplementary therapeutic agent in AD management.

Potential anticancer effect of free and nanoformulated Deferasirox for breast cancer treatment: in-vitro and in-vivo evaluation

Background Breast cancer (BC) stands as the second-leading cause of mortality among women worldwide. Many chemotherapeutic treatments for BC come with significant adverse effects. Additionally, BC is recognized as one of the most resistant forms of malignancy to treatment. Consequently, there exists a critical need for innovative therapeutic agents that are both highly effective and exhibit reduced toxicity and side effects for patients. Deferasirox (DFX), an iron-chelating drug approved by the FDA for oral use, emerges as a promising contender in the fight against BC proliferation. DFX, primarily administered orally, is utilized to address chronic iron excess resulting from blood transfusions, and it is the inaugural treatment for chronic iron overload syndrome. However, DFX encounters limitations due to its poor water solubility. Aim This study aimed at incorporating DFX into lipid nanocapsules (DFX-LNCs) followed by investigating the anticancer effect of the DFX nanoform as compared to free DFX in-vitro and on an orthotopic BC mouse model in-vivo. Methods The DFX-LNCs was prepared and imaged using TEM and also characterized in terms of particle size (PS), zeta potential (ZP), and polydispersity index (PDI) using DLS. Moreover, drug release, cytotoxicity, and anticancer effect were assessed in-vitro, and in-vivo. Results The results revealed that DFX-LNCs are more cytotoxic than free DFX with IC50 of 4.417 µg/ml and 16.114 µg/ml, respectively, while the plain LNCs didn’t show any cytotoxic effect on the 4T1 cell line (IC50 = 122.797 µg/ml). Besides, the apoptotic effect of DFX-LNCs was more pronounced than that of free DFX, as evidenced by Annexin V/PI staining, increased BAX expression, and decreased expression of BcL-2. Moreover, DFX-LNCs showed a superior antitumor effect in-vivo with potent antioxidant and anti-proliferative effects. Conclusion The newly developed DFX nanoform demonstrated a high potential as a promising therapeutic agent for BC treatment.

Screening of important factors using factorial design to predict simvastatin loaded solid lipid nanoparticles

This study aims to optimize Simvastatin-loaded Solid Lipid Nanoparticles (SLNs) using a 2^k factorial design approach. Simvastatin, a widely used cholesterol-lowering drug, faces bioavailability challenges, prompting the use of nanotechnology for drug delivery. The study focuses on lipid concentration, surfactant concentration, and homogenization speed as critical factors influencing SLN characteristics. These factors were chosen based on their potential impact on SLN physicochemical properties like particle size, polydispersity index, and drug entrapment efficiency. Through systematic variation of factor levels, a matrix of experiments will be created, measuring responses (particle size, polydispersity index, and drug entrapment efficiency) for each run. Statistical analysis, including ANOVA, will assess factor significance and interactions. The study aims to reveal critical parameters affecting Simvastatin-loaded SLN formulation. The optimized formulation targets uniform and stable nanoparticles with enhanced drug entrapment, enhancing Simvastatin bioavailability. The factorial design method offers a systematic, resource-efficient approach for simultaneously screening and optimizing multiple factors, streamlining the experimental process.Top of Form

Physiological and antimicrobial properties of a novel nanoemulsion formulation containing mixed surfactant and essential oils: Optimization modeling by response surface methodology

This research aims to optimize the parameters for the production of a stable nanoemulsion containing a mixture of essential oils (EOs) with a surfactant blend (Tween and Span 80) and assess its antimicrobial potency against spoilage bacteria and foodborne pathogens. The impact of a surfactant blend’s hydrophilic-lipophilic balance (HLB) as well as surfactant:oil ratio was investigated based on the mean particle size (z-average) and polydispersity index (PDI). Results showed HLB value of 12 and a ratio of surfactant to oil at 0.75:1 exhibited an emulsion with the smallest z-average and PDI. Following this, a response surface methodology (RSM) employing central composite design (CCD) was utilized to formulate an optimal nanoemulsion using the microfluidization (MF) technique. The RSM revealed that the microfluidizer pressure of 15,000 psi and 4 cycles produces a z-average of 38.11 nm, PDI of 0.27, ζ-potential of 37.8 mV, and encapsulation efficiency (EE) of 83.8%. The comparison between the experimental and anticipated results of the optimized nanoemulsion revealed no significant differences (p > 0.05). The optimal nanoemulsion displayed excellent stability during 30 days of storage at both 4 and 30 °C compared to 5 days for coarse emulsion. The nanoemulsion exhibited potent antimicrobial activity, showing minimum inhibitory concentration (MIC) values in the range of 0.019 to 0.156 μL/mL, surpassing the antimicrobial efficacy of the coarse emulsion, which had MIC values between 0.039 to 0.312 μL/mL. Thus, this study emphasized the efficacy of RSM design in developing an optimal nanoemulsion with enhanced antimicrobial properties using EOs, making it a promising natural food preservative.

Oat-based milk alternatives: the influence of physical and chemical properties on the sensory profile.

Oat-based milk alternatives (OMAs) have become increasingly popular, perhaps due to their low allergenicity and preferred sensory attributes when compared to other milk alternatives. They may also provide health benefits from unique compounds; avenanthramides, avenacosides, and the dietary fibre beta-glucan. This has led to a variety of commercial options becoming available. Being a fairly new product, in comparison to other plant-based milk alternatives (PBMAs), means little research has been undertaken on the sensory profile, and how it is influenced by the physical and chemical properties. This study investigated the sensory, physical and chemical profiles of current commercially available OMAs, that varied in fortification, use of stabilisers, and oat content. The volatile compounds and their respective aromas were analysed using solid phase microextraction followed by gas chromatography mass spectrometry (GC-MS) and gas chromatography-olfactometry (GC-O). Liquid chromatography mass spectrometry (LC-MS) was used for identification of avenanthramides and avenacosides. Particle size and polydispersity index (PDI) were analysed using a Mastersizer and Zetasizer, respectively, with colour analysis carried out using a colourimeter, and viscosity measurements using a rheometer. Descriptive sensory profiling was used to assess the impact on the sensory characteristics of the different samples and the sensory data acquired were correlated with the instrumental data. Samples with smaller particle size appeared whiter-both instrumentally and perceptually. The only clear plastic packaged product differed substantially in volatile profile from all other products, with a higher abundance of many volatile compounds, and high overall perceived aroma. Avenanthramides and avenacosides were present in all samples, but differed significantly in abundance between them. The results suggested smaller particle size leads to whiter colour, whilst differences in processing and packaging may contribute to significant differences in aroma. Astringency did not differ significantly between samples, suggesting that the variation in the concentrations of avenacosides and avenanthramides were below noticeable differences.

Cetuximab decorated redox sensitive D-alpha-tocopheryl- polyethyleneglycol-1000-succinate based nanoparticles for cabazitaxel delivery: Formulation, lung targeting and enhanced anti-cancer effects

This research work aims to fabricate cetuximab (CTX) decorated cabazitaxel (CBZ) loaded redox-sensitive D-alpha-tocopheryl-polyethyleneglycol-1000-succinate (TPGS-SS) nanoparticles (NPs) for epidermal growth factor receptor (EGFR)-targeted lung tumor therapy.The NPs were prepared using a dialysis bag diffusion method to produce, non-redox sensitive non targeted (TPGS-CBZ-NPs), redox-sensitive nontargeted (TPGS-SS-CBZ-NPs), and targeted redox-sensitive NPs (CTX-TPGS-SS-CBZ-NPs). Developed NPs were characterized for particle sizes, polydispersity, surface charge, surface morphologies, and entrapment efficiency. Moreover, additional in vitro studies have been conducted, including in vitro drug release, cytotoxicity, and cellular uptake studies.The particle size and charge over the surface were found to be in the range of 145.6 to 308.06 nm and −15 to –23 mV respectively. The IC50 values of CBZ clinical injection (Jevtana®), TPGS-CBZ-NPs, TPGS-SS-CBZ-NPs, and CTX-TPGS-SS-NPs were found to be 17.54 ± 3.58, 12.8 ± 2.45, 9.28 ± 1.13 and 4.013 ± 1.05 µg/ml, suggesting the 1.37, 1.89 and 4.37-folds respectively, enhancement of cytotoxicity as compared to CBZ clinical injection, demonstrating a significant augmentation in cytotoxicity. In addition, the in-vitro cellular uptake investigation showed that CTX-TPGS-SS-CMN6-NPs accumulated significantly compared to pure CMN6, TPGS-CMN6-NPs, and TPGS-SS-CMN6-NPs in the A549 cells. Furthermore, the targeting efficiency of developed NPs were analysed by ultrasound/photoacoustic and IVIS imaging.

Improvement in Pharmacological Activity of Mahkota Dewa (Phaleria macrocarpa (Schef. Boerl)) Seed Extracts in Nanoemulsion Dosage Form: In Vitro and In Vivo Studies.

Mahkota Dewa (Phaleria macrocarpa) seed has various phytochemical compounds and low pharmacological activities, including antioxidant and anti-inflammatory activities. This research aimed to study nanoemulsion preparations of Mahkota Dewa seed (NE-BMD) for their anti-oxidant and anti-inflammatory properties. The nanoemulsion was prepared using an ultrasonication probe and followed by selecting two formulations, F7 and F8. The anti-oxidant activity test was carried out using the DPPH method, meanwhile, the anti-inflammatory activity test was conducted using the protein denaturation method with Bovine Serum Albumin (BSA) for in vitro studies. In addition, for in vivo studies, the plethysmometer method was used with 1% carrageenan as an inducer. The characterization of NE-BMD preparations showed that the particle size and polydispersity index were 26,83 ± 1,27 nm (PI: 0.36 ± 0.03) and 30.73 ± 1.50 nm (PI: 0.32 ± 0.06) for NE-BMD F7 and F8 formulation, respectively. In addition, the anti-oxidant activity test revealed that the IC50 values of NE_BMD F7 and F8 were 15.62 ± 1.40 µg/ml and 28.39 ± 4.69 µg/ml, respectively. The protein denaturation test showed that the IC50 values for NE-BMD F7 and F8 were 94.39 ± 1.24 µg/ml and 196.63 ± 1.61 µg/ml, respectively. Meanwhile, the study of anti-inflammatory in vivo for NE-BMD F7 with a 1 g/kg BW dose showed a significant improvement in anti-inflammatory activity compared to BMD extract. This research suggests that due to the smaller drug particle size, the nanoemulsion dosage form of Mahkota Dewa seed extract has anti-oxidant and anti-inflammatory activities, thus emerging as an adjunct alternative treatment for inflammation.

Cation-crosslinked κ-carrageenan sub-microgel medium for high-quality embedded bioprinting

Three-dimensional (3D) bioprinting embedded within a microgel bath has emerged as a promising strategy for creating intricate biomimetic scaffolds. However, it remains a great challenge to construct tissue-scale structures with high resolution by using embedded 3D bioprinting due to the large particle size and polydispersity of the microgel medium, as well as its limited cytocompatibility. To address these issues, novel uniform sub-microgels of cell-friendly cationic-crosslinked kappa-carrageenan (κ-Car) are developed through an easy-to-operate mechanical grinding strategy. These κ-Car sub-microgels maintain a uniform submicron size of around 642 nm and display a rapid jamming-unjamming transition within 5 s, along with excellent shear-thinning and self-healing properties, which are critical for the high resolution and fidelity in the construction of tissue architecture via embedded 3D bioprinting. Utilizing this new sub-microgel medium, various intricate 3D tissue and organ structures, including the heart, lungs, trachea, branched vasculature, kidney, auricle, nose, and liver, are successfully fabricated with delicate fine structures and high shape fidelity. Moreover, the bone marrow mesenchymal stem cells encapsulated within the printed constructs exhibit remarkable viability exceeding 92.1% and robust growth. This κ-Car sub-microgel medium offers an innovative avenue for achieving high-quality embedded bioprinting, facilitating the fabrication of functional biological constructs with biomimetic structural organizations.

Step-By-Step Standardization of the Bottom-Up Semi-Automated Nanocrystallization of Pharmaceuticals: A Quality By Design and Design of Experiments Joint Approach.

Nanosized drug crystals have been reported with enhanced apparent solubility, bioavailability, and therapeutic efficacy compared to microcrystal materials, which are not suitable for parenteral administration. However, nanocrystal design and development by bottom-up approaches are challenging, especially considering the non-standardized process parameters in the injection step. This work aims to present a systematic step-by-step approach throughQuality-by-Design (QbD) and Design of Experiments (DoE) for synthesizing drug nanocrystals by a semi-automated nanoprecipitation method. Curcumin is used as a drug model due to its well-known poor water solubility (0.6µgmL-1, 25°C). Formal and informal risk assessment tools allow identifying the critical factors. A fractional factorial 24-1 screening design evaluates their impact on the average size and polydispersity of nanocrystals. The optimization of significant factors is done by a Central Composite Design. This response surface methodology supports the rational design of the nanocrystals, identifying and exploring the design space. The proposed joint approach leads to a reproducible, robust, and stable nanocrystalline preparation of 316nm with a PdI of 0.217 in compliance with the quality profile. An orthogonal approach for particle size and polydispersity characterization allows discarding the formation of aggregates. Overall, the synergy between advanced data analysis and semi-automated standardized nanocrystallization of drugs is highlighted.

Preparation of copolymer 7-hydroxyethyl chrysin loaded PLGA nanoparticles and the in vitro release.

To prepare 7-hydroxyethyl chrysin (7-HEC) loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles and to detect the in vitro release. The 7-HEC/PLGA nanoparticles were prepared by emulsification solvent volatilization method. The particle size, polydispersity index (PDI), encapsulation rate, drug loading and zeta potential were measured. The prescription was optimized by single factor investigation combined with Box-Behnken response surface method. Mannitol was used as protectant to prepare lyophilized powder, and the optimal formulation was characterized and studied for the in vitro release. The optimal formulation of 7-HEC/PLGA nanoparticles was as follows: drug loading ratio of 2.12∶20, oil-water volume ratio of 1∶14.7, and 2.72% soybean phospholipid as emulsifier. With the optimal formulation, the average particle size of 7-HEC/PLGA nanoparticles was (240.28±0.96) nm, the PDI was 0.25±0.69, the encapsulation rate was (75.74±0.80)%, the drug loading capacity was (6.98±0.83)%, and the potentiostatic potential was (－18.17±0.17) mV. The cumulative in vitro release reached more than 50% within 48 h. The optimized formulation is stable and easy to operate. The prepared 7-HEC/PLGA nanoparticles have uniform particle size, high encapsulation rate and significantly higher dissolution rate than 7-HEC.

Nanoscale Stolephorus sp. powder fabrication using high-energy milling for bioactive materials in dentistry.

The application of natural products in dentistry has been widely explored. Anchovy (Stolephorus in Latin) has been examined for its bioactive content (calcium, phosphorus and fluoride) as an agent for bone stimulation and tooth development, topical fluoridation and pulp capping. Ball milling has been used to prepare calcium oxide nanoparticles from snakehead fish bone. The aim of the study was to reduce the particle size of Stolephorus sp. powder to the nanoscale using high-energy ball milling for 8, 12 and 24 h, and to analyze the optimal milling time by comparing the powder characteristics. The Stolephorus sp. were oven-dried at 50°C for 6 h, after which the entire fish were crushed into powder. The fish powder was produced by blending the material for 5 min and passing it through a 200-mesh sieve. The remaining dried fish was blended again for 5 min until it passed through the sieve. The top-down approach to the particle size reduction was performed using high-energy milling at 3 distinct time points (8, 12 and 24 h). The characteristics of the powder were evaluated using a particle size analyzer, a Fourier-transform infrared spectrometer (FTIR) and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS). The Stolephorus sp. powder contained 64.50% protein, 7,420 mg/kg sodium, 28,912 mg/kg calcium, and 1,924 mg/kg magnesium. The high-energy milling process resulted in a reduction of the particle size from the microscale to the nanoscale. The analysis of the average particle size and polydispersity index indicated that 24 h of milling showed the most optimal results. Furthermore, the functional groups exhibited no significant alteration at 3 milling times (p ≥ 0.05, FTIR analysis). The high-energy milling method has the potential to reduce the particle size of Stolephorus sp. powder to the nanoscale at the 8- and 24-h milling periods. The powder resulting from the 24-h milling process had a size of 789.3 ±170.7 nm, smooth size distribution, good size uniformity, a polydispersity index of 0.763, no significant change in organic and inorganic compound content, and a calcium/phosphorus ratio that was the closest to that of hydroxyapatite (HAp).

Influence of the Reynolds number from Reτ = 150 to 210 on size-dependent bipolar charging

We recently found wall-bounded turbulence to suppress and control bipolar triboelectric charging of particles of identical material. This control is due to fluid modifying the motion of light particles. Thus, the particles’ charge distribution depends on their Stokes number distribution. More specifically, fluid forces narrow the bandwidth of the charge distribution, and bipolar charging reduces dramatically. Consequently, not the smallest but mid-sized particles collect the most negative charge. However, the influence of the Reynolds number or particle concentration on bipolar charging of polydisperse particles is unknown. This paper presents the charging simulations of same-material particles the in different wall-bounded flows. In a comprehensive study, we vary the Reynolds number from Reτ = 150 to 210 and the particle number density from 4 × 109m-3 to 1 × 1010m-3 to further explore the influence of the carrier flow on bipolar charging. We model charge transfer based on the balance of transferable charge species. Such species can represent adsorbed ions transferred during collisions or free electrons captured into a lower energy state on the other surface. The turbulent flow is modeled via Direct Numerical Simulations (DNS) and is coupled to the particulate phase modeled via the Discrete Element Method (DEM). Overall, our multiphysics approach couples the fluid dynamics, electric field, triboelectric charging, and particle momentum into one complex simulation.

Numerical Study of the Effect of Primary Nozzle Geometry on Supersonic Gas-Solid Jet of Bypass Injected Dry Powder Fire Extinguishing Device

A two-way coupled model between polydisperse particle phases with compressible gases and a density-based coupling implicit solution method, combining the third-order MUSCL with QUICK spatial discretization scheme and the second-order temporal discretization scheme, are constructed based on the discrete-phase model (DPM) and the stochastic wander model (DRWM) in the Eulerian–Lagrangian framework in conjunction with a unitary particulate source (PSIC) approach and the SST k-ω turbulence model. The accuracy of the numerical prediction method is verified using previous supersonic nozzle gas-solid two-phase flow experiments. Numerical simulation of a two-phase jet of dry powder extinguishing agent gas with pilot-type supersonic nozzle was performed to analyze the influence of geometrical parameters, such as the length ratio rL and the area ratio rA of the main nozzle on the two-phase flow field, as well as on the jet performance indexes, such as the particle mean velocity vp,a, velocity inhomogeneity Φvp, particle dispersion Ψp, particle mean acceleration ap,a, etc. By analyzing the parameters, we indicate the requirements for the combination of jet performance metrics for different flame types such as penetrating, spreading, and dispersing.

Effect of temperature and shear stress on properties of nanovesicles carrying hydrolyzed pollen protein

In this study, the effect of storage (65 °C, 24 h) and shear rates (2-100 s−1, 10 min) on the particle size, poly-dispersity index (PDI), encapsulation efficiency (EE), Angiotensin-converting enzyme (ACE) and DPPH radical inhibition, iron ion reduction ability and flow behavior of nanovesicles containing hydrolyzed bee pollen (produced by alcalase and pepsin) were evaluated. Nanoliposomes were coated by chitosan (0.2 % w/w). After storage at 65 °C, the size of the nanovesicles raised 2–2.5 folds while EE showed 5–8 % decline. ACE and DPPH radical inhibition activity were also decreased. After applying the shear stress, PDI was increased significantly (P<0.05), while EE of the nanoniosomes showed a drastic decline (P<0.05). Nanoliposomes and nanoniosomes exhibited decline in the ACE inhibitory and antioxidant activity. At low shear rates Newtonian-like and weak pseudo-plastic behavior of the chitosan-coated nanoliposomes were observed. The flow index (n), (k) and (R2) indicated the suitability of power law model for describing the flow characteristics.

Optimize the parameters for the synthesis by the ionic gelation technique, purification, and freeze-drying of chitosan-sodium tripolyphosphate nanoparticles for biomedical purposes

BackgroundPolymeric nanoparticles can be used for wound closure and therapeutic compound delivery, among other biomedical applications. Although there are several nanoparticle obtention methods, it is crucial to know the adequate parameters to achieve better results. Therefore, the objective of this study was to optimize the parameters for the synthesis, purification, and freeze-drying of chitosan nanoparticles. We evaluated the conditions of agitation speed, anion addition time, solution pH, and chitosan and sodium tripolyphosphate concentration.ResultsChitosan nanoparticles presented an average particle size of 172.8 ± 3.937 nm, PDI of 0.166 ± 0.008, and zeta potential of 25.00 ± 0.79 mV, at the concentration of 0.1% sodium tripolyphosphate and chitosan (pH 5.5), with a dripping time of 2 min at 500 rpm. The most representative factor during nanoparticle fabrication was the pH of the chitosan solution, generating significant changes in particle size and polydispersity index. The observed behavior is attributed to the possible excess of sodium tripolyphosphate during synthesis. We added the surfactants poloxamer 188 and polysorbate 80 to evaluate the stability improvement during purification (centrifugation or dialysis). These surfactants decreased coalescence between nanoparticles, especially during purification. The centrifugation increased the zeta potential to 40.8–56.2 mV values, while the dialyzed samples led to smaller particle sizes (152–184 nm). Finally, freeze-drying of the chitosan nanoparticles proceeded using two cryoprotectants, trehalose and sucrose. Both adequately protected the system during the process, and the sugar concentration depended on the purification process.ConclusionsIn Conclusion, we must consider each surfactant's benefits in formulations for selecting the most suitable. Also, it is necessary to do more studies with the molecule to load. At the same time, the use of sucrose and trehalose generates adequate protection against the freeze-drying process, even at a 5% w/v concentration. However, adjusting the percentage concentration by weight must be made to work with the CS-TPP NPs purified by dialysis.

A stable delivery system for curcumin: Fabrication and characterization of self-assembling acylated kidney bean protein isolate nanogels

The construction of protein-based nano-gels as curcumin delivery system effectively enhances the stability and bioavailability of curcumin. In this study, acylation modification and self-assembly techniques were jointly employed to construct acylated kidney bean protein isolate (AKBPI)-nanogels. Optimal conditions for AKBPI-nanogels were determined to be pH 7, concentration of 2 mg/mL, and temperature at 90℃ for 30 min. The optimized AKBPI-nanogels exhibited excellent uniformity as evidenced by decreasing average particle size (137.35 nm) and polydispersity index (0.38). Acylation enhanced the intermolecular interactions within the nanogel by reducing the polarity of tyrosine microenvironment and free sulfhydryl groups. AKBPI-nanogels demonstrated remarkable characteristics in terms of pH sensitivity, salt concentration, and storage tolerance. The curcumin-loaded AKBPI-nanogels exhibited an encapsulation efficiency of 92.30 % and maintained high antioxidant activity. In simulated gastrointestinal digestion, AKBPI-nanogels facilitated the controlled release and higher bioavailability of curcumin. Therefore, AKBPI-nanogels can be a stable tool for delivering curcumin.

Docosahexaenoic acid–mediated milk protein treated by ultrasound-assisted pH shifting for enhanced astaxanthin delivery and processed cheese application

Whey protein isolate (WPI)-based nanodelivery systems have recently attracted an increasing amount of attention. Despite this, research focusing on milk protein concentrate (MPC) and micellar casein (MCC) as carriers loaded in hydrophobic compounds is lacking. This study investigated the mediated effect of docosahexaenoic acid (DHA) in 3 different milk proteins for the embedding of astaxanthin (ASTA) after ultrasound-assisted pH-shifting treatment. We then evaluated the application of milk protein carriers in cheese processing by comparing MPC, MCC, and WPI. The particle size, polydispersity index, and zeta potential results of the milk protein-DHA complex suggested that the addition of 0.36 μmol/mL DHA optimized the delivery of milk protein to ASTA. All 3 DHA-mediated milk proteins induced an improvement in encapsulation efficiency and antioxidant properties of ASTA. Furthermore, the DHA-mediated MPC and MCC played a stronger role in improving the bioaccessibility, thermal and storage stability of ASTA than those without DHA. Tests conducted to examine the application in cheese production indicated that MCC carrier had a positive effect on the texture of cheeses. However, the delivery effect was dependent on the milk protein variety, in which MCC exhibited the best protection ability of ASTA, followed by MPC and WPI. The simulated digestion and storage stability results of cheese further confirmed that the protein encapsulation mediated by DHA was more conducive to ASTA absorption. These findings suggested that the DHA-mediated milk protein complexes studied here may be suitable hydrophilic delivery carriers for the hydrophobic nutrient ASTA, potentially playing different roles in regulating the storage stability and bioaccessibility.

CFPD-PK simulation of inhaled Delta-9-tetrahydrocannabinol aerosol dynamics: Transport, deposition, and translocation in a mouth-to-G10 subject-specific human airway

Medical cannabis is increasingly used as an alternative therapy for various conditions, including chronic pain, multiple sclerosis, epilepsy, and cancer-related symptoms. However, it is crucial to ensure that patients receive the intended dose of tetrahydrocannabinol (THC) from inhaled cannabis for optimal therapeutic effect without overdose risk. This requires a comprehensive understanding of the factors that influence the pharmacokinetics (PKs) of THC in the respiratory system. However, accurate estimation of lung dosimetry and blood concentration of inhaled THC remains challenging partially because the influence of diversified patient-specific puff patterns on inhaled THC transport, deposition, and translocation is still not well quantified. To address the knowledge gap mentioned above, this study employed a hybrid computational fluid-particle dynamics (CFPD) and PK model to evaluate factors that influence delivered doses of THC to the human respiratory system and the resultant THC-plasma concentration-time profile. Specifically, this study compared multiple puff waveforms for inhalation-holding-exhalation (IHE) with total puff volumes from 55 to 82 ml for 2 or 3 s, hold durations from 0 to 5 s, and three puff waveforms (i.e., square, sinusoidal, and realistic). THC deposition in the airways was recorded during all phases for each case using either 452,849 particles per second for the 1.128-μm monodisperse cases or 399,866 particles per second for the polydisperse cases, with the mass median aerodynamic diameter (MMAD) of 1.128 μm. Pulmonary air-THC particle flow transport dynamics, THC particle deposition data, and THC vapor absorption were predicted using CFPD for four airway regions, then scaled by region-specific bioavailability factors. The deposited THC mass in airway regions represents the initial mass entering a 3-compartment PK model, to predict the THC-plasma concentration-time profiles. The CFPD-PK results revealed significant variability in THC transport, deposition, and plasma concentration based on IHE factors. Specifically, larger puff volumes and longer holding times enhanced THC deposition in deeper airways and increased THC-plasma concentrations. Realistic transient puff waveforms predicted higher particle deposition and THC-plasma concentrations than simplified square waveforms. Polydisperse particle distributions show more realistic deposition patterns than monodisperse particle simulations. This study provides insights into the complexity of THC inhalation therapy, emphasizing the importance of considering individualized puff patterns and realistic particle size distributions in accurately predicting therapeutic outcomes, which is highly related to THC deposition in the lung and THC plasma concentration. These findings and the CFPD-PK modeling framework offer guidance for clinicians in prescribing personalized THC dosages, support regulatory science in evaluating inhalation devices, and contribute to ongoing research aimed at optimizing THC delivery for maximum therapeutic effectiveness while minimizing potential overdose risks.

Effect of Rosa damascena Essential Oil Loaded in Nanostructured Lipid Carriers on the Proliferation of Human Breast Cancer Cell Line MDA-MB-231 in Comparison with Cisplatin

PurposeAs Rosa damascena essential oils (RDEOs) have antioxidant, antibacterial, antiviral, and insecticidal activity, they could therefore be useful in the treatment of breast cancer. In the current study, an attempt was made to incorporate RDEO in a lipid-based drug delivery system, namely, nanostructured lipid carrier (NLC) to boost its anticancer effect compared to cisplatin.MethodsGas chromatography (GC) identified the chemical compositions of RDEO. RDEO-NLCs were prepared using the probe ultrasonication method. The obtained nanoparticles were characterized in terms of particle size, polydispersity index, and zeta potential by dynamic light scattering. The encapsulation efficiency of the formulations and their loading capacity were also determined, and transmission electron microscopy (TEM) was employed to evaluate the morphology of the optimal formulation (quoted as RDEO-NLC2). The anticancer effect of RDEO-NLC2 on MDA-MB-231 cells and apoptosis were assessed using MTT and in vitro cellular assays respectively.ResultsTEM result revealed a distinct spherical shape for RDEO-NLC2, with an average particle size of 78.39 ± 1.5 nm obtained by Zetasizer. The results also showed that the obtained particles had a negative surface charge (− 31.0 mV) with a polydispersity index of 0.28 ± 0.01. The chemotherapy drug cisplatin showed more cytotoxicity than RDEO-NLC2 against cancer cells. Cellular data demonstrated that RDEO-NLC2 like cisplatin can decline the viability of MDA-MB-231 cells through apoptosis compared to cells treated with the placebo and free RDEO.ConclusionRDEO-NLC2 has the ability to stimulate apoptosis in the human BC cell line MDA-MN-231; hence, it can be beneficial in the treatment of patients suffering from breast cancer.

Enhanced Stability and Improved Oral Absorption of Enzalutamide with Self-Nanoemulsifying Drug Delivery System.

The purpose of this study is to develop and evaluate a self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral absorption of poorly water-soluble enzalutamide (ENZ). Considering the rapid recrystallization of the drug, based on solubility and crystallization tests in various oils, surfactants and co-surfactants, Labrafac PG 10%, Solutol HS15 80%, and Transcutol P 10%, which showed the most stable particle size and polydispersity index (PDI) without drug precipitation, were selected as the optimal SNEDDS formulation. The optimized SNEDDS formulation showed excellent dissolution profiles for all the drugs released at 10 min of dissolution due to the increased surface area with a small particle size of approximately 16 nm. Additionally, it was confirmed to be stable without significant differences in physical and chemical properties for 6 months under accelerated conditions (40 ± 2 °C, 75 ± 5% RH) and stressed conditions (60 ± 2 °C). Associated with the high dissolutions of ENZ, pharmacokinetic parameters were also greatly improved. Specifically, the AUC was 1.9 times higher and the Cmax was 1.8 times higher than those of commercial products (Xtandi® soft capsule), resulting in improved oral absorption. Taken together with the results mentioned above, the SNEDDS could be an effective tool as a formulation for ENZ and other similar drugs.