Poor Solubility Research Articles

Novel N-phenyl-2-(aniline) benzamide hydrochloride salt development for colon cancer therapy

IntroductionN-phenyl-2-(aniline) analog N53 is a previously discovered dual inhibitor of Topo I and COX-2, which exhibited significant anti-colon cancer activity in vitro, but the poor solubility and moderate anti-cancer activity in vivo hindered its further development.MethodsTo rectify the suboptimal drug properties of N53, a series of salt forms were developed and further evaluated through in vivo and in vitro experiments.ResultsThe hydrochloride (N53·HCl) has a well-characterized crystal structure and its solubility reached 540.1 μg/mL, which is nearly 1,700 times higher than that of N53 (0.32 μg/mL). Increasing the N53 solubility consistently promotes its effective concentration, further enhancing the COX-2/Topo I inhibitory activity and the anti-tumor activity in vitro (IC50 values of 2.95 ± 0.08 μM for HT29 cells, 7.99 ± 0.85 μM for RKO cells, 10.94 ± 1.30 μM for HCT116 cells), as well as the anti-proliferative and pro-apoptotic activity. Meanwhile, its oral pharmacokinetic property in vivo is also improved. The elimination half-life (T1/2) is prolonged from 10.78 to 22.29 h, the maximum plasma concentration (Cmax) is increased 2-fold, and the area under the plasma drug concentration-time curve (AUC0–∞) is increased 3-fold. In colon cancer xenograft mouse models, the tumor inhibition rate of N53·HCl was 53.7%, superior to that of N53 (34.7%). Moreover, the results of HE staining showed that N53·HCl had no obvious toxic effects and side effects on other organs, indicating that it was safe in vivo.DiscussionThis study demonstrated that N53·HCl exhibits superior pharmacokinetic properties, anti-colon cancer efficacy, and safety, providing a promising drug candidate for colon cancer therapy.

Considerations and Challenges to Develop Drug-drug Coamorphous System: A Recent Update.

Poor water solubility of several drugs, especially BCS class II and IV drugs, restricts their dissolution and negatively affects oral absorption. Amorphization of drugs is a year-old approach to enhance solubility and dissolution of poorly water-soluble drugs. Polymeric amorphous systems have been proven effective but have disadvantages, such as low drug loading, high carrier content, etc. In a coamorphous system, a small molecule can be used as a coformer that keeps the amorphous form of a drug stable. In a drug-drug coamorphous system (CAS), one therapeutically active moiety can act as a coformer for the other drug. Although effective, the rationale of selecting the drugs and optimising the ratio without compromising therapeutic effect and safety is challenging. The preparation method is also a challenge because the stress during the processing method may result in the loss of crystallinity. Hence, the processing stability of the amorphous drug is a significant concern. A stable CAS is formed when two drugs generate some molecular-level interaction. In silico prediction of miscibility, molecular dynamic simulation, functional group analysis by Fourier Transform infrared spectroscopy, Raman spectroscopy, NMR, etc. contribute to the analysis of molecular-level interaction. Additionally, the article discusses the preparation method and the fact that the excipient must be selected carefully to form an effective CAS.

Ultrasound-assisted extraction of itraconazole from pellets: an efficient approach for the recovery of active pharmaceutical compounds from solid dosage forms

IntroductionItraconazole is a widely used broad-spectrum antifungal drug on a global scale. However, its poor water solubility necessitates the development of advanced formulations for its effective use. Currently, itraconazole is available commercially in capsule form, with pellets containing the active drug. The extraction of itraconazole from these granules is often required when developing new formulations. Extracting active pharmaceutical ingredients (APIs) from pellets is crucial in ensuring precise and consistent dosing when producing pharmaceutical dosage forms. Surprisingly, no existing methods for extracting itraconazole from pellets have been reported thus far.ObjectiveTherefore, this study aimed to develop and evaluate an efficient method for extracting this API from pellets.MethodsTwo extraction methods were assessed: conventional Soxhlet extraction and ultrasound-assisted extraction.Results and DiscussionThe results demonstrated that ultrasound-assisted extraction significantly outperformed the conventional method, yielding higher amounts of itraconazole with a high purity level of 96.8%.

Complexation of telmisartan with cyclodextrins as a tool of solubility enhancement: A comparative analysis of influence of the cyclodextrin type and method of solid dispersion preparation

Cardiovascular telmisartan (TMS) was complexed with modified cyclodextrins (CD) aiming at improvement of its poor solubility which results into low bioavailability. Inclusion complexes with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) in liquid and solid state was evaluated for first time. Phase solubility isotherm diagrams of TMS versus the CD concentration were plotted in a buffer pH 7.4. It was found that TMS/CD complexes are formed in solution in an equimolar stoichiometric ratio of 1:1. The aqueous solubility of TMS with the addition of 0.05 mol·L−1 HP-β-CD increased by 23 times and was 38.9·10−5 mol·L−1, and the presence of the same amount of SBE-β-CD in solution increased the solubility of the drug by 7 times, reaching a value of 12.6·10−5 mol·L−1.The binding constants were found to 468 and 114 L·mol−1 for HP-β-CD and SBE-β-CD, respectively. Novel solid forms of TMS with both CDs were prepared using the grinding and evaporation approaches. Successful formation of supramolecular TMS/HP-β-CD and TMS/SBE-β-CD solid complexes was confirmed by FTIR, PXRD, DSC, TGA and SEM. The residual crystallinity of all obtained solid dispersions of TMS/CD did not exceed 10 %. Supersaturation was observed during the dissolution of all the solid complexes. The grinding technique was found to be more advantageous as it ensured the biggest improvement of the drug maximum concentration in the aqueous solution: the TMS solubility in the TMS/HP-β-CD(gr) and TMS/SBE-β-CD(gr) solid complexes increased by 27 and 33 times, respectively. Besides, polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG) were tested as crystallization inhibitors. Addition of 1 wt% PVP as a stabilizer is a promising approach for the preparation of TMS pharmaceutical formulations with improved bioavailability.

Reimagining Anti-Inflammatory Drugs Delivery: The Integration of Ordered Mesoporous Silica and MOF Materials for Enhanced Therapeutic Outcomes

Abstract Migraine, one of the neurological conditions, affects approximately 15% of the global population. It is characterized by intense headaches accompanied by nausea, vomiting, and heightened sensitivity to light. The first line of drugs for treating migraine are non-steroidal anti-inflammatory drugs. Unfortunately, these medications suffer from poor solubility in water, uncontrolled release, and numerous adverse side effects. In order to maximize their therapeutic effect by preventing premature release and degradation, novel drug delivery systems based on composites are being dynamically developed. Herein, the biocompatible ketoprofen, naproxen sodium, and diclofenac sodium vehicles integrating ordered mesoporous silica (SBA-16) with Fe-based metal–organic frameworks (MIL-101(Fe)) were synthesized via the solvothermal method. The composites were characterized by different percentages of MIL-101(Fe) 
(25 and 50 wt.%), which had a significant impact on their porosity, structure, and number of functional groups. The SBA-16@MIL-101(Fe)-25 and SBA-16@MIL-101(Fe)-50 samples exhibited BET surface areas of 768 and 324 m2/g, respectively. Their sorption capacities towards selected anti-inflammatory drugs were in the range of 141-318 mg/g for ketoprofen, 481-490 mg/g for naproxen sodium, and 246-589 mg/g for diclofenac sodium, notably exceeding the values obtained for pure mesoporous silica (5-9 mg/g). Morphological defects and specific functional groups, derived from SBA-16 and MIL-101(Fe), contributed to generating new adsorption sites in composites, enhancing host-guest interactions. The drug release profiles were determined by the carrier porosity, surface charge, and the presence of functional groups. The diffusion of ketoprofen and diclofenac sodium from the composites into the phosphate buffer (pH 7.7), mimicking rectal fluid, occurred in a more controlled manner compared to pristine silica. The SBA-16@MIL-101(Fe)-50 carrier released 82% of ketoprofen and 90% of diclofenac sodium over 24 hours.

Enhancement of antibacterial activity in electrospun fibrous membranes based on quaternized chitosan with caffeic acid and berberine chloride for wound dressing applications.

Electrospun nanofibers made from chitosan are promising materials for surgical wound dressings due to their non-toxicity and biocompatibility. However, the antibacterial activity of chitosan is limited by its poor water solubility under physiological conditions. This study addresses this issue by producing electrospun nanofibers mainly from natural compounds, including chitosan and quaternized chitosan, which enhance both its solubility for electrospinning and the antibacterial activity of the resulting electrospun nanofibers. Additionally, antimicrobial agents like caffeic acid or berberine chloride were incorporated. The glutaraldehyde-treated nanofibers showed improved mechanical properties, with an average tensile strength exceeding 2.7 MPa, comparable to other chitosan-based wound dressings. They also demonstrated enhanced water stability, retaining over 50% of their original weight after one week in phosphate-buffered saline (PBS) at 37 °C. The morphology and performance of these nanofibers were thoroughly examined and discussed. Furthermore, these membranes displayed rapid drug release, indicating potential for inhibiting bacterial growth. Antibacterial assays revealed that S2-CX nanofibers containing caffeic acid were most effective against E. coli and S. aureus, reducing their survival rates to nearly 0%. Similarly, berberine chloride-containing S4-BX nanofibers reduced the survival rates of E. coli and S. aureus to 19.82% and 0%, respectively. These findings suggest that electrospun membranes incorporating chitosan and caffeic acid hold significant potential for use in antibacterial wound dressings and drug delivery applications.

A Pyrrole Modified 3,4-Propylenedioxythiophene Conjugated Polymer as Hole Transport Layer for Efficient and Stable Perovskite Solar Cells.

Despite the outstanding electric properties and cost-effectiveness of poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives, their performance as hole transport layer (HTL) materials in conventional perovskite solar cells (PSCs) has lagged behind that of widely used spirobifluorene-based molecules or poly(triaryl amine). This gap is mainly from their poor solubility and energy alignment mismatch. In this work, the design and synthesis of a pyrrole-modified HTL (PPr) based on 3,4-propylenedioxythiophene (ProDOT) are presented for efficient and stable PSCs. As a result of the superior defects passivation ability, excellent contact with perovskite, enhanced hole extraction, and high hydrophobicity, the unencapsulated PPr-based PSCs showed the peak PCE of 21.49% and outstanding moisture stability (over 4000 h). This work highlights the potential application of ProDOT-based materials as HTL for PSCs and underscores the importance of the rational design of PEDOT and its derivatives.

A modified self-micro emulsifying liposome for bioavailability enhancement of quercetin and its biological effects

Quercetin (QT) is a chief dietary flavonoid with a myriad of health benefits, however, its poor solubility and low bioavailability restrict its food application. Thus, the present study aimed at enhancing its solubility using a modified self-micro emulsifying system (QT-TPGS-QS). The stability of liposome was assessed via monitoring of its particle indexes (size, zeta potential, PDI, stability towards in-vitro digestion, drug release, and encapsulation efficiency). Further, antibacterial and cellular antioxidant potential of liposomes were determined. QT-TPGS-QS exhibited good optical clarity with a loading ratio of 2.1%. The liposome showed uniform spherical and regular shape (<100 nm) with a QT release rate of 85.61% ± 0.32% in simulated in-vitro digestion. QT-TPGS-QS demonstrated superior antibacterial activity compared to QT alone against Escherichia coli, Staphylococcus aureus, and Salmonella. In-vitro antioxidant evaluation confirmed that the QT-TPGS-QS exhibited a significantly higher free radical scavenging ability than QT alone. Cellular assay confirmed that QT-TPGS-QS (15 μg/mL) exhibited a good protection effect on oxidative stress induced by H2O2. Catalase (CAT) and glutathione peroxidase (GSH-Px) levels were significantly upregulated, concurrent with a reduction of malondialdehyde (MDA) suggesting that QT-TPGS-QS might be effective in inhibiting the production of intracellular reactive oxygen species (ROS), and to be considered as food additive or in nutraceuticals.

Optimized freeze-dried solid-dispersions boost naringin solubility, antibacterial and in-vitro anticancer activity

Naringin (NRG) is a water insoluble glycoside having wide range of therapeutic efficacy. Its efficacy is limited due to its poor water solubility and bioavailability. In the current research, solid dispersions (SDs) were prepared by freeze drying method using different carriers KollidonVA64, KollidonVA30, Soluplus and Poloxamer188. The prepared binary SDs were characterized for solubility and dissolution study to select the optimized composition and further ternary SDs was prepared with carrier blend (KollidonVA64 and Soluplus). Finally, the ternary SDs (F6) was evaluated for solid state characterization (DSC, XRD, SEM), drug polymer interaction (IR), in vitro antioxidant, antimicrobial as well as cell viability study against neuroblastoma cell. The binary SDs developed with KollidonVA64 and Soluplus showed greater solubility than KollidonVA30 and Poloxamer188. The ternary SDs (F6), showed a significant enhancement in the saturation solubility and dissolution than binary SDs (F1-F4). The binary SDs (F1-F4) displayed the maximum release in 120 min (73.5±2.8 to 94.6±3.1%), whereas the ternary SDs (F6) showed the maximum release in 60 min (99.2±1.6%). The spectroscopy results confirm the formation of a stable dispersion and no drug polymer interaction was observed. The thermogram, diffractogram and microscopic image confirms the conversion of crystalline NRG to amorphous form. These findings support the results of saturation solubility and dissolution data. The in vitro antioxidant, antimicrobial and cytotoxicity assessment displayed a greater activity of developed NRG SDs than the free NRG. The enhancement in the results may be due to the enhanced solubility of NRG after formation of SDs using the KollidonVA64 and Soluplus carrier blend.

QbD-driven Formulation Development and Evaluation of Genistein Nanoparticles for Prostate Cancer

Background: Genistein (GEN) shows significant anticancer potential, particularly against prostate cancer. However, its clinical application is limited by poor water solubility, rapid metabolism and excretion, low bioavailability, and lack of targeted delivery to cancer cells, hindering its effectiveness as a chemopreventive or therapeutic agent. Objective: In this study, poly-ε-caprolactone (PCL) nanoparticles incorporating polyvinyl alcohol (PVA) as a stabilizer were engineered to encapsulate genistein (GEN) effectively. Utilizing a Quality by Design (QbD) methodology, the development and optimization of these nanoparticles were systematically approached. Methods: GEN-loaded PCL nanoparticles (NPs) were prepared using the Solvent Evaporation Technique, ideal for encapsulating hydrophobic drugs. A Plackett–Burman design (PBD) identified key factors, followed by a Box–Behnken design (BBD) to optimize nanoparticle quality. The NPs were evaluated for particle size, zeta potential (ZP), polydispersity index (PDI), morphology, encapsulation efficiency (EE), in vitro drug release, and cytotoxicity. Results: The optimized formulation containing PCL, PVA, and Volume of organic solvent as 43.7 mg, 6.2 mg, and 10.0 ml, respectively was chosen because it showed EE (%) of 94.0%, average particle size of 150 nm, PDI of 0.10, ZP of -28.0 and exhibited sustained release of GEN for around four days. The antiproliferative activities of GEN PCL NPs were confirmed by the MTT test in vitro on malignant prostate carcinoma cell lines (PC3). Flow cytometric analysis showed that the inhibition of cell proliferation of more potent GEN PCL NPs is comparable with the effects of free GEN. Conclusion: The findings indicate that genistein-loaded PCL nanoparticles have the potential to augment the anticancer efficacy of genistein, both in vitro and in vivo. This suggests their promise as a viable candidate for prostate cancer treatment.

Bone Healing via Carvacrol and Curcumin Nanoparticle on 3D Printed Scaffolds.

Carvacrol is a potent antimicrobial and anti-inflammatory agent, while curcumin possesses antioxidant, anti-inflammatory, and anticancer properties. These phytochemicals have poor solubility, bioavailability, and stability in their free form. Nanoencapsulation can reduce these limitations with enhanced translational capability. Integrating nanocarriers with 3D-printedcalcium phosphate (CaP)scaffolds presents a novel strategy for bone regeneration. Carvacrol and curcumin-loaded nanoparticles (CC-NP) synthesized with melt emulsification produced negatively charged, monodispersed particles with a hydrodynamic diameter of ≈127nm. Their release from the scaffold shows a biphasic release under physiological and acidic conditions. At pH 5.0, the CC-NP exhibits a 53% release of curcumin and nearly 100% release of carvacrol, compared to 19% and 36% from their respective drug solutions. At pH 7.4, ≈40% of curcumin and 76% of carvacrol releases, highlighting their pH-sensitive release mechanism. In vitro studies demonstrate a 1.4-fold increase in osteoblast cell viability with CC-NP treatment. CC-NP exhibit cytotoxic effects against osteosarcoma cells, reducing cell viability by ≈2.9-fold. The antibacterial efficacy of CC-NP evaluated against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) exhibiting 98% antibacterial efficacy. This approach enhances therapeutic outcomes and minimizes the potential side effects associated with conventional treatments, paving the way for innovative applications in regenerative medicine.

Targeted Delivery of Celastrol by GA-Modified Liposomal Calcium Carbonate Nanoparticles to Enhance Antitumor Efficacy Against Breast Cancer

Background/Objectives: Breast cancer, a leading health threat affecting millions worldwide, requires effective therapeutic interventions. Celastrol (CEL), despite its antitumor potential, is limited by poor solubility and stability. This study aimed to enhance CEL’s efficacy by encapsulating it within glycyrrhizic acid (GA)-modified lipid calcium carbonate (LCC) nanoparticles for targeted breast cancer therapy. Methods: The 4T1 mouse breast cancer cells were used for the study. GA-LCC-CEL nanoparticles were prepared using a gas diffusion method and a thin-film dispersion method. GA-LCC-CEL were characterized using the zeta-potential, dynamic light scattering and transmission electron microscope (TEM). The in vitro release behavior of nanoparticles was assessed using the in vitro dialysis diffusion method. Cellular uptake was examined using flow cytometry and confocal microscopy. Intracellular ROS and Rhodamine 123 levels were observed under fluorescence microscopy. MTT and colony formation assays assessed cytotoxicity and proliferation, and apoptosis was analyzed by Annexin V-FITC/PI staining. Wound healing and transwell assays evaluated migration, and Western blotting confirmed protein expression changes related to apoptosis and migration. Results: GA-LCC-CEL nanoparticles displayed a well-defined core-shell structure with a uniform size distribution. They showed enhanced anti-proliferative and pro-apoptotic effects against 4T1 cells and significantly reduced breast cancer cell invasion and migration. Additionally, GA-LCC-CEL modulated epithelial-mesenchymal transition (EMT) protein expression, downregulating Snail and ZEB1, and upregulating E-cadherin. Conclusions: GA-LCC-CEL nanoparticles represent a promising targeted drug delivery approach for breast cancer, enhancing CEL’s antitumor efficacy and potentially inhibiting cancer progression by modulating EMT-related proteins.

Curcumin Administration Routes in Breast Cancer Treatment.

Breast cancer is a public health concern worldwide, characterized by increasing incidence and mortality rates, requiring novel and effective therapeutic strategies. Curcumin is a bioactive compound extracted from turmeric with several pharmacological activities. Curcumin is a multifaceted anticancer agent through mechanisms including the modulation of signaling pathways, inhibition of cell proliferation, induction of apoptosis, and production of reactive oxygen species. However, the poor water solubility and bioavailability of curcumin create important barriers in its clinical application. This review elaborates on the therapeutic potential of curcumin in breast cancer treatment, focusing on the efficacy of different administration routes and synergistic effects with other therapeutic agents. The intravenous administration of curcumin-loaded nanoparticles significantly improves bioavailability and therapeutic outcomes compared to oral routes. Innovative formulations, such as nano-emulsifying drug delivery systems, have shown promise in enhancing oral bioavailability. While intravenous delivery ensures higher bioavailability and direct action on tumor cells, it is more invasive and expensive than oral administration. Advancing research on curcumin in breast cancer treatment is essential for improving therapeutic outcomes and enhancing the quality of life of patients.

Molecular Engineering of membrane structure targeted photosensitizers for antitumor photodynamic therapy

Photodynamic therapy (PDT) has been used to cure special diseases or the diseases that localized at special sites in comparison with conventional therapy, due to its high spatiotemporal selectivity, non-invasion, low drug resistance. However, vast majority of photosensitizers (PSs) still suffer from several limitations including poor aqueous solubility and poor photostability. Here, we used two strategies, promoting the intramolecular charge transfer and terminal modification, to overcome these limitations and enhance therapeutic effects. Three membrane-structure targeted molecules, 3CN-Np, 3CN–OH, and 3CN-QA, were designed and synthesized, which exhibited high extinction coefficient, excellent photostability and reactive oxygen species (ROS) productive capacity. In cell imaging, the designing molecules would stain endoplasmic reticulum for 3CN-Np and 3CN–OH, and cell membrane for 3CN-QA, respectively. Afterwards, we used white light (25 mW/cm2) to irradiate the probe cultured cells for 20 min, the ratio of the dead and live cells was 3.0 for 3CN-Np, 3.5 for 3CN–OH, and 3.7 for 3CN-QA. Based on the high cell apoptosis in vitro under a white-light, 3CN–OH was selected to inhibited tumor growth in vivo, and the tumor volume was reduced to 45 % with non-toxicity to vitals. The study provided new sights in developing PSs with high water-solubility, photostability, and ROS generating ability in white-light mediating PDT system.

Antimycobacterial Activity of Solid Lipid Microparticles Loaded with Ursolic Acid and Oleanolic Acid: In Vitro, In Vivo, and Toxicity Assessments

Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate their anti-Mtb efficacy in vitro and in vivo, as well as their acute toxicity. SLMs measured 0.7–0.89 µM in size, with complete in vitro release of OA and UA at 40 and 32 h, respectively. The minimum inhibitory concentration (MIC) of SLMs loaded with OA and UA was 40 µg/mL SLMs + 20 µg/mL OA + 20 µg/mL UA for drug-sensitive Mtb and 80 µg/mL SLMs + 40 µg/mL OA + 40 µg/mL UA for multidrug-resistant (MDR) Mtb. These SLMs showed an efficient reduction in Mtb burden in infected alveolar macrophages. In a murine model of late-stage progressive MDR-TB, aerosolized delivery of SLMs containing OA and UA via a metered-dose inhaler significantly reduced pulmonary bacterial loads and extended survival. In vivo, acute toxicity studies revealed no mortality or signs of toxicity. These findings demonstrate that SLMs are an optimal delivery system for terpenoids, providing potent in vitro and in vivo anti-TB activity with an excellent safety profile.

Colistin-niclosamide-loaded nanoemulsions and nanoemulsion gels for effective therapy of colistin-resistant Salmonella infections.

Colistin (COL) is regarded as a last-resort treatment for infections by multidrug-resistant (MDR) Gram-negative bacteria. The emergence of colistin-resistant Enterobacterales poses a significant global public health concern. Our study discovered that niclosamide (NIC) reverses COL resistance in Salmonella via a checkerboard assay. However, poor solubility and bioavailability of NIC pose challenges. In this study, we prepared a self-nanoemulsifying drug delivery system (SNEDDS) co-encapsulating NIC and COL. We characterized the physicochemical properties of the resulting colistin-niclosamide-loaded nanoemulsions (COL/NIC-NEs) and colistin-niclosamide-loaded nanoemulsion gels (COL/NIC-NEGs), assessing their antibacterial efficacy in vitro and in vivo. The COL/NIC-NEs exhibited a droplet size of 19.86 nm with a zeta potential of -1.25 mV. COL/NIC-NEs have excellent stability, significantly enhancing the solubility of NIC while also demonstrating a pronounced sustained-release effect. Antimicrobial assays revealed that the MIC of COL in COL/NIC-NEs was reduced by 16-128 times compared to free COL. Killing kinetics and scanning electron microscopy confirmed enhanced antibacterial activity. Antibacterial mechanism studies reveal that the COL/NIC-NEs and COL/NIC-NEGs could enhance the bactericidal activity by damaging cell membranes, disrupting proton motive force (PMF), inhibiting multidrug efflux pump, and promoting oxidative damage. The therapeutic efficacy of the COL/NIC-NEs and COL/NIC-NEGs is further demonstrated in mouse intraperitoneal infection models with COL-resistant Salmonella. To sum up, COL/NIC-NEs and COL/NIC-NEGs are a potentially effective strategies promising against COL-resistant Salmonella infections.

Advancing Liposomal Coating Approaches for Improved Anticancer Drug Delivery.

Quercetin, a natural flavonoid with antioxidant, anti-inflammatory, and anticancer properties, faces limitations in clinical application due to its poor solubility and bioavailability. This study presents a novel delivery system utilizing a combination of polyoxyethylene (100) stearyl ether and folic acid to enhance quercetin's effectiveness. We developed folate-conjugated polyoxyethylene (100) stearyl ether-coated liposomes (FA-Brij-LPs) to leverage the unique properties of polyoxyethylene (100) stearyl ether in conjunction with folic acid for targeted delivery. The FA-Brij-LPs were prepared using the thin-film hydration method and characterized for their physicochemical properties, including size, zeta potential, and drug loading capacity. The optimized FA-Brij-LPs exhibited a mean particle size of 147.57 nm, a zeta potential of 32.20 mV, and a drug loading capacity of 9.33%. In vitro studies demonstrated sustained quercetin release and significantly enhanced cellular uptake compared to free quercetin. The Resazurin cell viability assay further revealed superior anticancer efficacy of FA-Brij-LPs. This innovative approach underscores the effectiveness of combining polyoxyethylene (100) stearyl ether with folic acid in enhancing quercetin delivery and its potential applications in cancer therapy.

An Overview of the Cancer Targeting Attributes of the Elastin Like Polypeptide Nano‐Carriers: Discerning Active and Passive Modes

AbstractSince the 1940s, generalized cytotoxic therapy has been a valuable tool in cancer treatment. Over the years, there's been a significant increase in developing potential cytotoxic drugs. However, little progress has been made in enhancing patients' quality of life. The therapeutic index is limited due to the drug's poor solubility and lack of selectivity. Various carriers have been explored for drug delivery to enhance efficacy. Yet, there's a gap for a versatile delivery system that can adjust to specific drug and application requirements. Here, a multifaceted drug delivery platform based on a genetically engineered nature‐inspired polymer, elastin‐like polypeptide (ELP) is introduced. This technology enables the customization of the polymeric vehicle's physicochemical characteristics to suit the needs of a specific drug and application. The review highlights ELP's advantages in cancer targeting, such as site‐specificity, controlled release, biocompatibility, and extended plasma circulation. For the first time, ELP‐based drug delivery into passive and active targeting for better comprehension of its adaptability is classified. Moreover, numerous opportunities for loading different types of drugs onto the polymer are outlined. Finally, the polymer's efficacy in delivery across multiple cancer types, underscoring the wide spectrum of ELP‐based cancer drug delivery is precisely described.

Prolonged Retention of Albumin Nanoparticles Alleviates Renal Ischemia-Reperfusion Injury through Targeted Pyroptosis.

Acute kidney injury (AKI) represents a prevalent and complex clinical event, characterized by irreversible damage to renal tubular epithelial cells and high intensive care unit (ICU) admission rates and mortality. The kidneys are highly susceptible to oxidative stress, inflammation, pyroptosis, and programmed cell death. Pyroptosis poses a significant risk, exacerbating the damage and inflammation of renal tubular cells. Disulfiram (DSF), an FDA-approved medication for alcohol cessation, inhibits the pyroptotic pore-forming protein Gasdermin-D (GSDMD), positioning it as a potential solution for emergency relief against an inflammatory response. However, current obstacles include poor water solubility, rapid metabolism, and off-target effects. Inspired by this discovery, bovine serum albumin (BSA), which has already entered clinical application, has been utilized to produce safe and long-lasting nanoparticles (BSA@DSF NPs), addressing the challenges posed by DSF's physicochemical properties. By targeting the GSDMD protein, the potent pro-inflammatory effects of pyroptosis were mitigated, leading to the alleviation of AKI induced by ischemia-reperfusion injury. This research offers a straightforward and efficient concept for treating AKI, potentially enhancing the transition to clinical practice.

Lentil protein and trehalose conjugates: Structural interactions and mechanisms for improving multi-level structure and functional characteristics.

This study aimed to improve lentil proteins' (LPs) functionality and nutritional value, specifically addressing their lower water solubility and digestibility. A unique combination of LP-disaccharide interactions was employed. Spectroscopic technologies, which include fluorescence spectra, ultraviolet spectra, and Fourier-transform infrared, investigated the structure of LPs at various concentrations of trehalose. The results indicate that the LP structures and conformation were considerably modified (p<0.05) following trehalose conjugation. The surface charge and hydrophobicity of the trehalose-conjugated LPs (T-LPs) were significantly altered (p<0.05), from -22.7 to -31.4 and 753 and 543 a.u., respectively. Furthermore, the digestibility and solubility of T-LPs increased from 75% to 81.8% and 60% to 66%, respectively. In conclusion, this study showed that combining LPs and trehalose conjugation could improve the quality of conjugates LPs, which could expand their use in manufacturing as the acceptance of plant-based diets increases. PRACTICAL APPLICATION: Currently, lentil proteins (LPs) are used in plant-based protein powders and supplements. Though less popular than soy or pea proteins, LPs are valued for their high protein content and good amino acid profile. LPs are utilized in meat alternatives and high-protein snack products. The application of these products is mainly due to their nutritional benefits rather than functional properties due to their poor water solubility. Increasing the water solubility of LPs could significantly expand their application in various food industries, making LPs a more competitive and functional plant-based protein source. Trehalose-conjugated LPs with better water solubility allow LPs to be used in other food products, such as plant-based protein beverages. Better solubility would enhance the clarity and smoothness of these products, making them more appealing to consumers.