Solvent Injection Research Articles

TECHNOLOGIES FOR DEPOSIT VOLUME ASSESSING IN AN OIL PIPELINE

Deposits of various compositions in the pipelines of oil and gas companies significantly worsen the conditions for transporting fluids between field facilities, their presence increases energy consumption and the possibility of accidents with environmental consequences. In sections where bullets are not using, the most effective way to remove asphalt-resin-paraffin deposits (ARPD) is to use compounds of organic solvents selected in laboratory conditions. One of the factors of their successful application is a preliminary assessment of the deposit volume in a complicated pipeline. The article examines a horizontal section of an oil pipeline with ARPD, closed at both ends, filled with oil with a residual content of associated petroleum gas after the first stage separator. Pressure reduction and the appearance of a certain volume of gas in a free state is initiated in the oil pipeline. The deposit volume is calculated on the basis of a mathematical formula during the injection of an organic solvent of the first portion with an information component.

Investigation of the usefulness of collagen peptide in intramyocardial injection of human iPS cell-derived cardiomyocytes

Abstract Background Injecting human induced pluripotent stem (iPS) cell-derived cardiomyocytes directly into the heart muscle holds promise as a treatment for heart failure. Achieving better engraftment is crucial for maximizing therapeutic effectiveness. Collagen peptide (CP) is a form of hydrolyzed gelatin known for its resistance to solidification. By adjusting its concentration, the viscosity of CP can be easily managed, potentially influencing the retention and engraftment efficiency of transplanted cells. Purpose We investigated the impact of different CP concentrations as a solvent for intramyocardial injection of human iPS cell-derived cardiomyocytes. Methods Initially, we examined the leakage of CP solution from the injection site using chicken meat and ex vivo rat heart. Subsequently, an in vivo experiment was conducted using beating rat myocardium injected with CP solution and Indian ink to assess CP diffusion in dynamic heart tissue. Finally, we performed intramyocardial injections of human iPS cell-derived cardiomyocytes onto a myocardial infarction model in immunosuppressed rats (1.0×107 cells/rat), followed by echocardiographic evaluation of cardiac function four weeks post-transplantation (N=3-6). Results There was less leakage from the injection site at lower CP concentration (10%) compared to higher concentration (20%), particularly in chicken or ex vivo rat heart tissue under static, non-beating conditions (chicken; 10% vs. 20% CP: 3.2±0.7% vs. 11.6±0.8%, P=0.01 / rat heart; 1.5±0.9% vs. 6.8±1.1%, P=0.0072). However, when examining fluid leakage from the cross-section of ex vivo rat hearts, we observed significantly higher leakage, regardless of CP concentration (10% CP: 45.7±2.7%, 20% CP: 59.1±8.1%), suggesting that CP diffusion within myocardial tissues had a greater influence on local retention than leakage from the injection site. Subsequently, in an experiment using beating rat myocardium and Indian ink, we observed significant suppression of diffusion in tissues treated with CP solution, with the 20% concentration showing a tendency to remain at the injection site (0% CP: 24.5±6.2 mm2, 10% CP: 6.9±7.1 mm2, 20% CP: 10.6±3.3 mm2, P=0.005). This indicates that 20% CP, rather than 10% CP, may be more suitable for local retention in tissues experiencing intra-tissue pressure, such as the beating myocardium. Finally, in vivo experiment using a myocardial infarction model of rat, there was no significant difference in left ventricular ejection fraction (LVEF) when cardiomyocytes were transplanted with 10% CP (0％ CP: 56.1±8.9%, 10%CP: 61.9±5.2%, P=0.92). However, there was a trend towards improved LVEF with the 20% CP solution (0% CP: 56.1±8.9%, 20%CP: 68.8±7.9%, P=0.13), Conclusion Twenty-percent CP may be more beneficial for treating myocardial ischemia due to enhanced retention and engraftment of transplanted cardiomyocytes.

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.

Regulation of hepatic transporters OATP1A2 and OATP1B1 by the action of nitric oxide (II)

Nitric oxide II (NO) is a signaling molecule that has a wide range of physiological effects, including the regulation of gastrointestinal processes. The liver actively expresses the clinically significant transporters OATP1A2 and OATP1B1, which are involved in the influx of biologically active and medicinal substances. That is why it seems relevant to determine the pathways of regulation of hepatic transporters under the influence of NO. Aim. To study the effect of NO on the relative amount and expression of the transporters OATP1A2 and OATP1B1 in vitro in HepG2 cells. Materials and methods. The study was performed on a culture of HepG2 cells, which were cultured in 6-well plates at 37 °C and 5% CO2 in Dulbecco’s modified Eagle’s medium (DMEM) with a high glucose content (4500 mg/l) containing L-glutamine (4 mM), 10% fetal bovine serum, 100 U/ml penicillin and 100 mg/ml streptomycin (all components from Sigma-Aldrich, Germany). S-nitrosoglutathione (Sigma-Aldrich, Germany) was added to the culture medium at concentrations of 1, 10, 50, 100 and 500 µM, incubated for 24 and 72 hours. Water for injection (solvent) was added to control cells in an equivalent volume S-nitrosoglutathione). The relative amounts of OATP1A2 and OATP1B1 proteins were assessed by Western blot, and the expression of SLCO1A2 and SLCO1B1 by real-time PCR. The results of the study. In the course of this study, it was shown that the addition of S-nitrosoglutathione in the concentration range of 10-500 μM and exposure duration of 24 and 72 hours causes an increase in the intracellular level of nitric oxide metabolites, which indicates the adequacy of the use of this NO donor. At the same time, under the influence of NO, there was an increase in the relative amount of the studied transporters - OATP1A2 at an exposure period of 24 hours and S-nitrosoglutathione concentrations of 50 and 100 μM, OATP1B1-24 and 72 hours, at concentrations of 10-500 μM, a similar trend was noted for the expression genes SLCO1A2 and SLCO1B1. Conclusion. The NO donor - S-nitrosoglutathione causes an increase in the relative amount of OATP family transporters - OATP1A2 and OATP1B1, due to increased expression of the SLCO1A2 and SLCO1B1 genes, in vitro in HepG2 cells.

Enhancing resveratrol pharmacokinetics and cytotoxicity in ovarian cancer cells via nanostructured lipid carriers

Resveratrol (Res), a potent nutraceutical, holds promise in ameliorating cancer and catalyzing breakthroughs in cancer therapy. Despite numerous preclinical studies on its anticancer activity, translational research progress remains limited. Poor pharmacokinetics and low potency are primary bottlenecks of Res therapy. In this study, we aimed to enhance the pharmacokinetic profile of Res in a rat model and assess its cytotoxicity against human ovarian cancer cells by developing Res loaded Nanostructured Lipid Carriers (Res-NLCs). The Res-NLCs were synthesized using the solvent injection method, featuring a size of 177 nm, a PDI of 0.25, and an entrapment efficiency exceeding 80%. The formulation exhibited stability for three months at 4 °C and 40 °C. Cytotoxicity assessments using the MTT assay and cellular uptake studies on human ovarian cancer cells (PA1 and SKOV3 luc) revealed significantly superior time-dependent cytotoxic effects and cellular accumulation of Res-NLCs compared to free Res. Pharmacokinetic studies of intravenously administered Res in NLCs demonstrated prolonged plasma levels of Res for at least 48 h. Remarkably, Res-NLCs exhibited approximately 15- and 5-fold improvements in AUC and elimination half-life (t1/2), respectively, compared to Res in solution in rats. Moreover, Res tissue distribution from Res-NLCs in rats showed significantly higher accumulation in the liver, lungs, and ovaries over 48 h, underscoring the potential for targeted therapy. In conclusion, NLCs effectively mitigated premature reduction of Res in the bloodstream, prolonged circulation period, and enhanced tissue accumulation. These findings suggest promising prospects for improving therapeutic outcomes in ovarian cancer therapy using Res-NLCs.

Overcoming the Strong Sample Solvent Effect for Sustainability Measurement Challenges in Liquid Chromatography. Example for Bisphenol-A.

This paper describes an approach to achieve low parts per billion (ppb) concentration level detection using a reversed-phase ultrahigh-performance liquid chromatographic ultraviolet absorbance detection method with large-volume feed injection (FI) for analytes in dichloromethane (DCM). FI is a novel technology that allows sample injection at a defined speed into the LC mobile phase. We demonstrate this approach for a mixture of bisphenol A and its diglycidyl ether derivatives in DCM. DCM is a very strong injection solvent at reversed-phase LC conditions and is typically immiscible with a starting reversed-phase gradient mobile phase containing a high percentage of water. As a result, reduced separation performance and even peak splitting are seen with classic flow-through injection. The method setup comprised an octyl-bonded core-shell stationary phase (150 × 4.6 mm i.d., 2.7 μm particle size) with a water/acetonitrile mobile phase gradient and an exceptionally high injection volume of 45 μL of DCM solution using FI. Optimization of feed speed (1%) and isocratic hold duration (4 min) was crucial for final separation conditions. FI delivered more than a 20-fold improvement in the limit of detection (LOD) compared to standard flow-through injection while maintaining peak resolution. The LOD of the final method ranged between 1 and 10 ppb in the polymer resin. This methodology has high potential for trace analysis in a large variety of applications that suffer from the "strong solvent effect".

Stacking in electrophoresis by electroosmotic flow-assisted admicelle to solvent microextraction.

An in-line sample concentration method for capillary electrophoresis called admicelle to solvent microextraction was proposed. In this technique, analytes were trapped in the cetyltrimethylammonium bromide admicelles formed in situ on the negatively charged capillary surface. A solvent plug was then partially injected hydrodynamically to collapse the admicelles, which liberated and focused the analytes at the solvent front. Voltage was applied across the capillary, completing the stacking process. Various solvents, namely, methanol, ethanol, and acetonitrile, were investigated. The optimal solvent for solvent to admicelle microextraction was 30% acetonitrile in 24mM sodium tetraborate (pH 9.2). Sample injection time and solvent to sample injection ratio were also optimised. For this demonstration, the optimum sample injection time and solvent to sample injection ratio were 320s and 1:2, respectively. Using the optimum conditions, UV detection sensitivity was enhanced 132-176-fold for the model anions. The LOQ, %intra-/inter-day (n = 6/n = 12, 2days) repeatability, and linearity (R2) of admicelle to solvent microextraction were 0.08-2µg/mL, 1.9-3.9%, 2.8-4.9%, and 0.992, respectively. Admicelle to solvent microextraction was applied to the analysis of various fortified water samples, with good repeatability (%RSD = 0.5-3.6%), and no matrix interferences.

A Study of Dimethyl Ether-Steam Coinjection Using a Large-Scale Physical Model

Summary Dimethyl ether (DME) as a water-soluble solvent has been studied as a potential additive to steam for improving the energy efficiency of steam-assisted gravity drainage (SAGD). The main objective of this research was to study in-situ flow characteristics and energy efficiency of DME-SAGD using a large-scale physical model. Results from DME-SAGD were compared with the control experiment of SAGD with no solvent injection using the same experimental setup. The main novelty of this research lies in the experimental data that demonstrated enhanced bitumen drainage by DME-SAGD in comparison with SAGD. The experiment was conducted in a cylindrical pressure vessel with a diameter of 0.425 m and a length of 1.22 m, which contained a sandpack with a porosity of 0.34 and a permeability of 5.0 darcies. The DME-SAGD experiment used a DME concentration of 10 mol% and a steam coinjection rate of 27.6 cm3/min [cold-water equivalent (CWE)] at 3000 kPa. Temperature distributions within the sandpack, along with injection and production histories, were recorded during the experiment. Subsequently, numerical simulations were performed to history match the experimental data, and the calibrated simulation model was used to analyze the details of compositional flow characteristics. Results showed that the 10 mol% DME-SAGD experiment yielded a recovery factor (RF) of 92.7% in 4.2 days, and the SAGD experiment yielded an RF of 68.6% in 6.0 days; for both experiments, the first 2 days were the preheating and the steam-only injection (SAGD) stages. The peak rate of bitumen production was 43.8 mL/min in the DME-SAGD experiment, which was more than twice greater than the peak rates observed in the SAGD experiment. The substantially increased rate of bitumen production resulted in a cumulative steam/oil ratio in DME-SAGD that was less than half of that in SAGD. Analysis of experimental results indicated that the solubility of DME in the aqueous and oleic phases caused different flow characteristics between DME-SAGD and SAGD. For example, the oleic and aqueous phases were more uniformly distributed in the sandpack in the former. Simulations indicated that DME-SAGD had a greater distribution of grid-scale inverse mobility ratio and increased oleic-phase mobilities in comparison with SAGD.

Prolonged Skin Retention of Luliconazole from SLNs Based Topical Gel Formulation Contributing to Ameliorated Antifungal Activity.

The development of effective therapy is necessary because the patients have to contend with long-termtherapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certainshortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. Thesolubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug.

‘Supercharged’ Shale EOR: A Liquid-Hydrocarbon-Based Approach Enters the Fray

Around a decade of research and testing has passed by, and the unconventional sector has yet to show that natural gas huff-and-puff can scale effectively across tight-oil fields. This doesn’t mean enhanced oil recovery (EOR) in shale is a lost cause. Though it does suggest that the industry needs alternatives to the first and most well-known method. Proof of this can be found in North Dakota’s Bakken Shale where researchers, operators, and a firm called EOR ETC have tried to show that the water-alternating-gas method is a cheaper, less gas-intensive way of adding incremental barrels. EOR ETC has indicated on its website that ExxonMobil subsidiary XTO Energy is currently testing the technology. Chevron has also recently shared how it has rethought shale EOR methods by designing a program for production-boosting surfactant injections and gas injections that can be done with artificial lift instead of giant compressors. Another emerging shale EOR concept goes a step further, arguing that the unconventional sector should abandon natural gas injections altogether. Denver-based Shale Ingenuity proposes that liquid-hydrocarbon solvents should be used instead. Shale Ingenuity has patented a process called SuperEOR, which it claims delivered a strong showing during its initial field test in the Eagle Ford Shale of south Texas. After nearly a year of cyclic solvent injections, which began in early 2023, a horizontal well with a 4,400-ft lateral and 16 fracture stages produced 44% more oil than its previous total output. This resulted in a 30-fold boost in flow rate, from 13 to 391 B/D. Building on its initial success, Shale Ingenuity informed JPT that two private producers in the Permian Basin and the Eagle Ford have selected its EOR technology for upcoming projects. Both will involve single four-well pads, with EOR operations expected to begin in 2026. The solvents used in the pilot consisted mostly of natural gas liquids (NGL)—ethane, propane, butane, and pentane. Shale Ingenuity said formulations may include other hydrocarbon and nonhydrocarbon liquids. While the bulk of these products flow straight out of thousands of wellheads in the US shale sector, Shale Ingenuity emphasizes that the key to unlocking their potential for EOR lies in its proprietary method of blending, or “tuning,” the solvents based on formation and crude oil properties. This allows the injected solvents to quickly mix with and help mobilize the residual oil droplets that are trapped in tight-rock formations, according to the company. Robert Downey, founder and CEO of Shale Ingenuity, explained the process. “The tuned solvents we are using have a minimum miscibility pressure (MMP) of 700 to 900 psi, which means it doesn’t take much pressure to drive them into solution. When pumped into the well, they instantly become miscible with oil, and as the formation heats up and the well is reopened, the solvents expand back into gas at 100 to 200 times their liquid volume.” The effect of all this is what he describes as a “supercharging” of the solution gas drive mechanism that promotes the strong early well flow shale wells are known for. This is the energy released by dissolved gas in the oil as it expands during the pressure drop brought on by producing the well.

A dynamic solvent chamber propagation estimation framework using RNN for warm solvent injection in heterogeneous reservoirs

Warm solvent injection (WSI), injecting low-temperature solvent into formations to reduce the viscosity of heavy oil, is a clean technology for heavy oil production through reducing greenhouse gas emissions and water usage. The success of WSI operation depends on the uniform development and propagation of solvent chambers in reservoirs. However, reservoir heterogeneity stemming from shale barriers plays a detrimental role in the conformance of solvent chamber development and oil production rate. In this work, we developed a novel recurrent neural network (RNN)-based framework with the capability of efficiently tracking and estimating the solvent chamber positions in heterogeneous reservoirs based on only production time-series data. The developed estimation model utilizes the “sequence-to-sequence" mapping methodology to correlate observed production time-series sequence and solvent chamber edge sequence via a long short-term memory (LSTM) algorithm. The trained RNN models exhibit high accuracy, evidenced by the predicted dynamic solvent chamber locations match the corresponding true locations from numerical simulation, with a high coefficient of determination (R2) and a low mean squared error. Specifically, the achieved R2 values exceed 0.98 on both the training and testing data. The developed RNN-based workflow was tested via several cases from both regularly- and irregularly-shaped shale barriers, and the results were promising. The predicted solvent chambers showed strong agreement with those obtained from numerical simulations. The major benefits of this workflow include reducing computational time and saving overall monitoring and tracking costs for conventional techniques. The present work would provide a good demonstration of the capability of practical integration of machine learning methods in solving engineering problems.

Technology Progress in High-Frequency Electromagnetic In Situ Thermal Recovery of Heavy Oil and Its Prospects in Low-Carbon Situations

Heavy oil resources are abundant globally, holding immense development potential. However, conventional thermal recovery methods such as steam injection are plagued by high heat loss, substantial carbon emissions, and significant water consumption, making them incompatible with carbon reduction goals and the sustainable socioeconomic development demands. A new method of high-frequency electromagnetic in situ heating, which targets polar molecules, can convert electromagnetic energy into heat so as to achieve rapid volumetric heating of the reservoir. This method has the potential to overcome the drawbacks of traditional techniques. Nevertheless, it faces significant drawbacks such as limited heating range and inadequate energy supply during later production stages, which necessitates auxiliary enhancement measures. Various enhancement measures have been reported, including nitrogen injection, hydrocarbon solvent injection, or the use of nano-metal oxide injections. These methods are hindered by issues such as pure nitrogen being easy to breakthrough, high costs, and metal pollution. Through extensive literature review, this article charts the evolution of high-frequency electromagnetic in situ heating technology for heavy oil and the current understanding of the coupled heat and mass transfer mechanisms underlying this technology. Moreover, based on a profound analysis of the technology’s progression trends, this work introduces a new direction: CO2-N2 co-injection as an enhancement strategy for high-frequency electromagnetic in situ heavy oil recovery. There is promising potential for the development of new technologies in the future that combine high efficiency, low carbon emissions, environmental friendliness, economic viability, and energy conservation. Furthermore, some research prospects in low-carbon situations and challenges for the new technology in future are presented in detail. All in all, the contribution of the paper lies in the summarizing of some main drawbacks of current enhanced electromagnetic in situ thermal recovery methods, and presents a novel research direction of using CO2-N2 co-injection as an enhancement strategy based on its current research status in low-carbon situations.

Molecular Dynamics Simulation of Lipid Nanoparticles Encapsulating mRNA.

mRNA vaccines have shown great potential in responding to emerging infectious diseases, with their efficacy and stability largely dependent on the delivery vehicles-lipid nanoparticles (LNPs). This study aims to explore the mechanisms by which LNPs encapsulate mRNA, as well as the effects of different N/P ratios and acid types in nucleic acid solutions on the structure and properties of LNPs, using the ethanol solvent injection method as the encapsulation technique. Six systems were designed, based on the composition and proportions of the existing mRNA vaccine mRNA-1273, and molecular dynamics (MD) simulations were employed to investigate the self-assembly process of LNPs. Ethanol was used as a solvent instead of pure water to better mimic experimental conditions. The results indicate that lipid components self-assemble into nanoparticles under neutral conditions, with the ionizable lipid SM-102 predominantly concentrating in the core of the particles. Upon mixing with nucleic acids in acidic conditions, LNPs undergo disassembly, during which protonated SM-102 encapsulates mRNA through electrostatic interactions, forming stable hydrogen bonds. Cluster structure analysis revealed that the four lipid components of LNPs are distributed sequentially from the outside inwards as DMG-PEG 2000, DSPC, cholesterol, and protonated SM-102. Moreover, LNPs constructed under low pH or low N/P ratios using citric acid exhibited larger volumes and more uniform distribution. These findings provide a scientific basis for further designing and optimizing LNP components to enhance the efficacy of mRNA vaccine encapsulation.

Ocena skuteczności oczyszczania strefy przyodwiertowej

The article discusses issues related to methods of treatment of the bottomhole zone of wells and assessment of its effectiveness. Analyses of a large volume of field material have shown that the most effective treatments for oil fields at a late stage of operation include injection of solvents, the use of acid-containing micro-emulsions, acid treatment, and the use of foam systems. The study proposes a method for identifying the factors that have the greatest impact on the efficiency of geological and technical activities. This approach allows for the correct selection of wells for treatment and the evaluation of the effectiveness of the measures implemented, aiding in determining their potential for further use. For production wells selected for near-wellbore treatment, it is crucial to accurately assess the economic efficiency post-treatment. This requires evaluating changes in the permeability of the near-wellbore zone following treatment. Therefore, in these wells, the “pressure build-up curve” (PBC) is recorded both before and after treatment. The increase in current production due to acid treatment of the near-well zone is determined by comparing production levels before and after treatment. The overall increase in oil production is determined by comparing the well’s production curve prior to development with the actual curve following development. When treating the bottomhole zone, it is essential to consider the well as part of a larger system of interacting objects, where improving the characteristics of one object does not necessarily enhance the operation of the entire system. The effectiveness of treating the bottomhole zone with solvents is significantly influenced by factors such as the percentage of resins in the product, the specific gravity of oil before treatment, the specific gravity of the solvent, and the viscosity of the oil.

HER-2 Receptor and αvβ3 Integrin Dual-Ligand Surface-Functionalized Liposome for Metastatic Breast Cancer Therapy.

Human epidermal growth factor receptor-2 (HER2)-positive breast cancer metastasis remains the primary cause of mortality among women globally. Targeted therapies have revolutionized treatment efficacy, with Trastuzumab (Trast), a monoclonal antibody, targeting HER2-positive advanced breast cancer. The tumor-homing peptide iRGD enhances the intratumoral accumulation and penetration of therapeutic agents. Liposomes serve as versatile nanocarriers for both hydrophilic and hydrophobic drugs. Gefitinib (GFB) is a potential anticancer drug against HER2-positive breast cancer, while Lycorine hydrochloride (LCH) is a natural compound with anticancer and anti-inflammatory properties. This study developed TPGS-COOH-coated liposomes co-loaded with GFB and LCH, prepared by the solvent injection method, and surface-functionalized with Trast and iRGD. The dual surface-decorated liposomes (DSDLs) were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), surface chemistry, surface morphology, and their crystallinity during in-vitro drug release, drug encapsulation, and in-vitro cell line studies on SK-BR-3 and MDA-MB-231 breast cancer cells. The half-maximum inhibitory concentration (IC-50) values of single decorated liposomes (SDLs), iRGD-LP, and Trast-LP, as well as DSDLs (iRGD-Trast-LP) on SK-BR-3 cells, were 6.10 ± 0.42, 4.98 ± 0.36, and 4.34 ± 0.32 μg/mL, respectively. Moreover, the IC-50 values of SDLs and DSDLs on MDA-MB-231 cells were 15.12 ± 0.68, 13.09 ± 0.59, and 11.08 ± 0.48 μg/mL, respectively. Cellular uptake studies using confocal laser scanning microscopy (CLSM) showed that iRGD and Trast functionalization significantly enhanced cellular uptake in both cell lines. The wound-healing assay demonstrated a significant reduction in SDL and DSDL-treated MDA-MB-231 cell migration compared to the control. Additionally, the blood compatibility study showed minimal hemolysis (less than 5% RBC lysis), indicating good biocompatibility and biosafety. Overall, these findings suggest that TPGS-COOH-coated, GFB and LCH co-loaded, dual-ligand (iRGD and Trast) functionalized, multifunctional liposomes could be a promising therapeutic strategy for treating HER2-positive metastatic breast cancer.

Antitumoral activity of a CDK12 inhibitor in colorectal cancer through a liposomal formulation

Colorectal cancer (CRC) is the third most common cancer worldwide. Recent experiments suggest that CDK12 can be a good therapeutic target in CRC, and therefore, novel inhibitors targeting this protein are currently in preclinical development. Lipid-based formulations of chemical entities have demonstrated the ability to enhance activity while improving the safety profile. In the present work, we explore the antitumor activity of a new CDK12 inhibitor (CDK12-IN-E9, CDK12i) and its lipid-based formulation (LP-CDK12i) in CRC models, to increase efficacy. SW620, SW480 and HCT116 CRC cell lines were used to evaluate the inhibitor and the liposomal formulation using MTT proliferation assay, 3D invasion cultures, flow cytometry, Western blotting and immunofluorescence experiments. Free-cholesterol liposomal formulations of CDK12i (LP-CDK12i) were obtained by solvent injection method and fully characterized by size, shape, polydispersity, encapsulation efficiency, and release profile and stability assessments. LP-CDK12i induced a higher antiproliferative effect compared with CDK12i as a free agent. The IC50 value was lower across all cell lines tested, leading to a reduction in cell proliferation and the formation of 3D structures. Evaluation of apoptosis revealed an increase in cell death, while biochemical studies demonstrated modifications of apoptosis and DNA damage components. In conclusion, we confirm the role of targeting CDK12 for the treatment of CRC and describe, for the first time, a liposomal formulation of a CDK12i with higher antiproliferative activity compared with the free compound.

Fluconazole-Niosome-Laden Contact Lens: A Promising Therapeutic Approach for Prolonged Ocular Delivery and Enhanced Antifungal Activity

BackgroundTraditional routes of administration of fluconazole such as eye drops have a low therapeutic efficacy due to insufficient bioavailability.PurposeHerein, a fluconazole noisome-laden contact lens was prepared to control and prolong the drug release and improve its bioavailability.MethodsTwo methods have been used to prepare fluconazole niosomes: solvent injection method and thin film hydration method utilizing span 60 and cholesterol mixture. Subsequently, formulations were optimized using three factors and a two-level factorial design and were subjected to in-vitro characterization for the size of niosomes, zeta potential, entrapment efficiency percent, and cytotoxicity study. The optimized fluconazole niosomes were further entrapped in contact lenses by the soaking method and were evaluated according to in-vitro release profile, and antimicrobial activity.ResultsThe results revealed that the investigated fluconazole niosomes are of nano-size ranging from 228.2 to 769.2 nm with zeta-potential values between − 18.1 and − 60.2 mV. The entrapment efficiency percentage ranged from 51.3 to 75%. Fluconazole was released from fluconazole noisome-laden contact lens and showed a prolonged release up to 48–72 h with a cumulative release of 79.62%. Statistical analysis showed that fluconazole-noisome-laden contact lenses have a significant impressive fungal adhesion reduction as compared to fluconazole-laden contact lenses.ConclusionFluconazole noisome-laden contact lenses are a promising therapeutic way for effective and prolonged treatment of ocular fungal infection.

Investigation of nano-confinement effects on asphaltenic crude oil phase behavior in tight and shale reservoirs: Modeling using CPA-EOS

As a result of strong molecule–molecule and molecule–wall interactions, phase behavior in confined fluids differs significantly from that in bulk fluids. Asphaltene precipitation is a challenging issue for both conventional and unconventional (nano-scale) porous media. In this study, a new model based on cubic-plus-association equation of state (CPA-EOS) was developed for studying phase behavior of asphaltenic crude oil and asphaltene precipitation in nanoporous media. The developed model considers confinement phenomena including shift in the critical properties of components, high capillary pressure, and adsorption/desorption of fluid components on rock surface. For this purpose, necessary modifications were performed on both the EOS and phase equilibria calculations. The developed model was then used to analyze two-phase (vapor–liquid) and three-phase (vapor–liquid–asphaltene) behavior in confined systems. Results demonstrated that confinement phenomena shrink the two-phase envelope and shift the critical point of the mixture. It is also shown that instability of asphaltene in the solution is higher in nanoporous media and increases with reducing pore size. Therefore, the amount of precipitated asphaltene in nanoporous media is higher than that in conventional systems. As adsorption of components with higher molecular weights is more than that of low-molecular weight compounds, the crude oil sample is enriched with lighter components and hence, due to adsorption, bubble point pressure increases, upper branch of dew point curve shifts downward and its lower branch shifts upward, and asphaltene instability increases. Neglecting confinement phenomena results in overestimation or underestimation of saturation pressures as well as asphaltene upper and lower onset points and the proposed model can be of high importance in predicting the extent of asphaltene precipitation during natural depletion or solvent injection in tight oil reservoirs.

Toward a large-batch manufacturing process for silicon-stabilized lipid nanoparticles: A highly customizable RNA delivery platform

While lipid nanoparticles (LNPs) are a key enabling technology for RNA-based therapeutics, some outstanding challenges hinder their wider clinical translation and use, particularly in terms of RNA stability and limited shelf life. In response to these limitations, we developed silicon-stabilized hybrid lipid nanoparticles (sshLNPs) as a next-generation nanocarrier with improved physical and temperature stability, as well as the highly advantageous capacity for “post-hoc loading” of RNA. Nevertheless, previously reported sshLNP formulations were produced using lipid thin film hydration, making scale-up impractical. To realize the potential of this emerging delivery platform, a manufacturing process enabling multikilogram batch sizes was required for successful clinical translation and deployment at scale. This was achieved by developing a revised protocol based on solvent injection mixing and incorporating other process adjustments to enable in-flow extrusion of multiliter volumes, while ensuring sshLNPs with the desired characteristics. Optimized procedures for nanoparticle formation, extrusion, and tangential flow filtration (TFF, to remove residual organic solvent) currently enable production of 2 kg finished batches. Importantly, sshLNPs produced via the modified large-scale workflow show equivalent physical and functional properties to those derived from the earlier small-scale methods, paving the way for GMP manufacturing protocols to enable vital translational clinical studies.

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders: drug stability, targeting efficiency, and safety.

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied. However, their inability to cross the blood-brain barrier hampers the clinical translation of these therapeutic strategies. Liposomes are nanoparticles composed of lipid bilayers, which can effectively encapsulate drugs and improve drug delivery across the blood-brain barrier and into brain tissue through their targeting and permeability. Therefore, they can potentially treat traumatic and nontraumatic central nervous system diseases. In this review, we outlined the common properties and preparation methods of liposomes, including thin-film hydration, reverse-phase evaporation, solvent injection techniques, detergent removal methods, and microfluidics techniques. Afterwards, we comprehensively discussed the current applications of liposomes in central nervous system diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and brain tumors. Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials. Additionally, their application as drug delivery systems in clinical practice faces challenges such as drug stability, targeting efficiency, and safety. Therefore, we proposed development strategies related to liposomes to further promote their development in neurological disease research.