Limited Water Solubility Research Articles

Formation of Inclusion Complex of Curcumin and Tetrahydrocurcumin Prevents Angiogenesis by Inhibiting VEGF Activity: An in-Silico Study

Curcumin and tetrahydrocurcumin (THC) are known for their anticancer properties, but limited solubility in water hinders their effectiveness against cancer. In this study, we conducted an in silico exploration of β-cyclodextrin's potential to form inclusion complexes with curcumin or THC. The aim of this study was to assess the potential of curcumin and THC inclusion complexes to inhibit vascular endothelial growth factor (VEGF) signaling pathway, a key element in carcinogenesis. The in silico analysis involved multiple stages, such as bioactive compound preparation, biological activity prediction, 3D structure retrieval of VEGF and VEGFR, protein-ligand docking, and visualization. The results of the study demonstrated that both the curcumin- and THC-inclusion complexes exhibit a lower requirement for binding free energy to interact with VEGFR compared to curcumin or THC molecules alone. When VEGFR binds with curcumin, the curcumin-inclusion complex, or the THC-inclusion complex before interacting with VEGF, there is a notable increase in the binding free energy for the VEGF-VEGFR interaction. Specifically, the presence of THC-inclusion complex demonstrates the highest binding free energy for the VEGF-VEGFR interaction. The molecular dynamic simulation study shows that when VEGFR binds with curcumin, curcumin-inclusion complex, or THC-inclusion complex, the fluctuation of amino acid residues in VEGFR decreases compared to the VEGFR protein structure before binding with these molecules. In conclusion, this study suggests that the formation of inclusion complexes holds considerable promise for enhancing the anticancer potential of curcumin and THC by augmenting their anti-angiogenic activity.

Enhancing the efficacy of nano-curcumin on cancer cells through mixture design optimization of three emulsifiers

Curcumin, a vital bioactive compound found naturally, has diverse biological applications. However, a major limitation of curcumin is its low bioavailability caused by its limited solubility in water. Hence, it is possible to overcome this problem through preparing oil in water nanodispersion of curcumin that emulsifier can play key role to produce nanodispersion. In the present study, the effect of three emulsifiers of Tween 80, Arabic Gum and Polyethylene glycol on preparing nanodispersions with desirable properties was investigated using subcritical water method and a mixture design. Zeta-potential and particle size of the achieved nanodispersions were taken into account as outcome factors. The optimum values for emulsifiers of Tween 80, Arabic Gum and Polyethylene glycol were obtained as 0.588 g, 0.639 g and 0.273 g, respectively, using the suggested model, so that obtained nanodispersion had minimum particle size (101.89 nm) and maximum zeta-potential (−24.99 mV). In fact, 102.5 nm and − 24.7 mV were obtained from experimental data at these values of emulsifiers. In addition, maximum loading potential (0.199 g/L), efficiency (99.5%), and minimum total curcumin loss (0.5%) were acquired at these optimum values. The results also show that the nanodispersion had a powerful antioxidant activity (65.27%) with extra antibacterial activity in facing with both E. coli and S. aureus strains. Moreover, curcumin nanodispersion was significantly taken up by HT-29 cells and resulted in the production of oxidative stress in the cells, leading to a decrease in the growth of cancer cells.

Lemongrass essential oil micro- and nanoencapsulation for industrial application: Production techniques and potential applications.

Due to its characteristic aroma and diverse therapeutic properties, lemongrass essential oil (LEO) has garnered increased attention in the pharmaceutical, food, and cosmetic industries. However, LEO's volatile nature, low chemical stability, and limited solubility in water limits its applications in the industry. Micro- and nanoencapsulation technologies emerge as a promising solution to overcome these challenges. A systematic methodology involving keyword searches in databases was employed to gather relevant literature on LEO micro- and nanoencapsulation, providing an extensive overview of techniques, processes, encapsulating materials, and possible applications. Beyond established methods, emerging techniques were explored. This review highlights the critical role of encapsulation in enhancing the thermal and chemical stability, applicability, bioavailability, and controlled release of LEO.

Placenta-anchored tadalafil liposomes rescues intrauterine growth restriction through continuous placental blood perfusion improvement

Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases.

Encapsulation and protection of β-carotene in Pickering emulsions stabilized by chitosan-phytic acid-cyclodextrin nanoparticles

β-Carotene is a hydrophobic molecule that can be isolated from plants that acts as a natural pigmen and nutraceutical. However, the limited water-solubility, oxidative-stability, and bioavailability limit its utilization in functional food, supplement, and pharmaceutical products. Pickering emulsions stabilized by chitosan-phytic acid-cyclodextrin (CS-PA-CD) nanoparticles were prepared to improve the delivery, stability, and bioavailability of β-carotene. The impact of nanoparticle concentration (0.1%, 0.5%, 1.0%, 1.5%, 2.0% w/v) and oil phase fraction (30%, 40%, 50%, 60%, 70% v/v) on the stability of β-carotene-loaded Pickering emulsions was investigated. The Pickering emulsions that were most stable to phase separation were formed at intermediate oil concentrations (50%-60% v/v). The encapsulated β-carotene exhibited improved resistance to heating (70 °C) and UV light exposure. Moreover, the bioaccessibility of β-carotene was also improved using a simulated gastrointestinal model. Overall, our findings highlight the potential of CS-PA-CD nanoparticles for forming and stabilizing Pickering emulsion-based delivery carrier for hydrophobic bioactive substances.

A review on solubility enhancement technique for pharmaceutical drugs

Solubility, a critical parameter governing the bioavailability and therapeutic efficacy of pharmaceutical compounds, often poses a significant challenge in drug development. This review article offers a thorough examination of several methods used to improve the solubility of medications that have low solubility, in order to overcome their limits. The discussion encompasses both conventional and emerging strategies, highlighting their mechanisms, advantages, and limitations. The study examines conventional methods such as particle size reduction, solid dispersion, and cosolvency, focusing on their historical importance and extensive use. Advances in nanotechnology, including nanosuspensions, nanocrystals, and lipid-based nanocarriers, are discussed for their potential to revolutionize solubility enhancement through improved drug delivery systems. An essential determinant in achieving optimal medication dosage absorption into the circulatory system is the demonstration of a pharmacological action is directly linked to the solubility of a substance. The primary challenge in formulating the new medicinal chemical is its limited water solubility. Medications with low solubility in water need large doses in order to achieve their highest effective concentration in the bloodstream when taken orally. The biopharmaceutical categorization system (BCS) classifies substances according to their solubility and permeability. Regulatory agencies and health organizations have used this categorization approach to validate bioequivalence for chemicals that are both highly soluble and very permeable by using dissolution as a form of confirmation. Medications that have a poor capacity to dissolve in water have a slow pace of breaking down, which results in a reduction in the amount of the medication that may be absorbed into the bloodstream when taken orally.

Inflammation-Responsive Cell Membrane-Camouflaged Nanoparticles against Liver Fibrosis via Regulating Endoplasmic Reticulum Stress and Oxidative Stress.

Liver fibrosis represents a reversible stage of various chronic liver diseases that progresses to cirrhosis. This condition is characterized by an imbalance between tissue damage and repair, and the production of fibers in the liver exceeds their degradation. Oxidative stress (OS) resulting from tissue injury and endoplasmic reticulum stress (ERS) triggered by the overproduction of proteins are pivotal factors in liver fibrosis. Melatonin demonstrates the capability to neutralize free radicals, shielding cells from oxidative harm. It is also a specific inhibitor of the ERS receptor transcription activating factor 6 (ATF6), indicating its great potential in ameliorating liver fibrosis. However, its limited water solubility and oral bioavailability of under 15% present hurdles in achieving therapeutic blood concentrations for treating liver fibrosis. The PLGA@Melatonin is constructed by loading melatonin with poly (lactic-co-glycolic acid) (PLGA). Platelet membranes (PM) and activated hepatic stellate cell membranes (HSCM) with high expression of the platelet-derived growth factor receptor (PDGFR) are extracted to successfully construct PM@PLGA@Melatonin and HSCM@PLGA@Melatonin, which are subsequently utilized to treat mice with liver fibrosis. The results illustrated the remarkable therapeutic effects of the two nanoparticles on liver fibrosis, along with their excellent targeting and biosafety properties.

In silico Toxicity and Pharmaceutical Properties to Get Candidates for Antitumor Drug

Background: Drug metabolism is a crucial aspect of medical practice and pharmacology, involving the transformation of drugs by various bodily systems to create compounds that are more easily eliminated from the body. Sorafenib was reported as a useful adjuvant treatment in patients with hepatocellular carcinoma who underwent surgical resection. However, poor pharmacokinetic properties such as limited water solubility, rapid elimination and metabolism lead to low bioavailability, restricting its further clinical application. Rosmarinic acid, soluble in ethanol and found in Rosemary leaves, has demonstrated therapeutic benefits in conditions such as cancer, diabetes, inflammatory disorders, neurodegenerative disorders, and liver disease. 
 Method: In silico is a term for experiments or tests carried out using computer simulation methods. In silico testing has emerged as a valuable approach for initiating the exploration of novel drug compounds or enhancing the efficacy of existing ones. This method involves predicting, generating hypotheses, and uncovering potential breakthroughs in medicine and therapy through virtual simulations.
 Results: Caco2 value of Sorafenib ligand as a comparison, namely 0.762. The highest Caco2 value is owned by Betulinic Acid and the value The lowest Caco2 is owned by Rosmarinic Acid. The highest sample HIA value was owned by Ursolic Acid and the lowest was owned by Rosmarinic Acid. Meanwhile, Sorafenib's HIA value is 85,494. ligands such as Carnosol and rosmanol have a high distribution volume, while the Sama carnosic league, ursolic acid and betulinic acid have a low distribution volume. The Rosmarinic acid ligand has a good distribution volume of 0.393, while the distribution volume value of Sorafenib is -0.009. The highest BBB sample value was owned by Carnosol and the lowest was owned by Rosmarinic acid. Meanwhile, the comparison ligand has a value of -1.473 and is considered less distributed in the brain. all ligands such as Carnosic Acid, Carnosol, Rosmanol, Ursolic Acid, Betulinic Acid, Rosmarinic acid do not have mutagenicity and Cytotoxic effects, but have an effect on immunity. The comparison ligand Sorafenib turned out to have effects on hepatotoxicity, immunity and cytotoxicity.
 Conclusion: In pharmacokinetic research, the six phenolic acid compounds in Rosemary exhibited superior properties compared to the reference ligand Sorafenib.

Enhancing oral bioavailability of andrographolide using solubilizing agents and bioenhancer: comparative pharmacokinetics of Andrographis paniculata formulations in beagle dogs

Context The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility. Objective This work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in Andrographis paniculata (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer. Materials and methods Four groups of beagles were compared: (1) A. paniculata powder alone (control), (2) A. paniculata powder with 50% weight/weight (w/w) β-cyclodextrin solubilizer, (3) A. paniculata powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) A. paniculata powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. All groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days. Results Thirteen chemical compounds were identified in A. paniculata powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. A. paniculata co-administration with either 50% w/w β-cyclodextrin or 1% w/w SDS, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces. Conclusion The combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for A. paniculata formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted.

Resveratrol-loaded pH-responsive Mesona chinensis polysaccharides-zein nanoparticles for effective treatment of ulcerative colitis.

Resveratrol (Res) is promising food functional factor with favorable antioxidant and anti-inflammatory properties, although its poor water solubility and low bioavailability limit extensive application. Therefore, in combination with another promising polysaccharide (Mesona chinensis polysaccharides, MCP), Res-loaded food nanocarriers (ResNPs) were developed to increase its water solubility, bioactivity and targeting properties. ResNPs were then applied to alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis. Resveratrol can be well encapsulated in MCP-based nanoparticles in an amorphous state, improving its water solubility. ResNPs showed pH-response controlled release behavior in the gastrointestinal tract and increased the enrichment of Res in the colon. In vivo experiments of ResNPs against DSS-induced ulcerative colitis (UC) revealed that ResNPs significantly improved UC symptoms, modulated intestinal inflammation and down-regulated oxidative stress levels compared to free Res. ResNPs also play an positive role with respect to inhibiting the mitogen-activated protein kinase pathway and promoting the expression of tight junction proteins. In addition, ResNPs improved the species composition and relative abundance of intestinal flora in UC mice, which effectively regulated the balance of intestinal flora and promoted the production of short-chain fatty acids. These results suggest that MCP-based nanoparticles can effectively improve the solubility of resveratrol and enhance its in vivo bioactivity. Moreover, the present study also provides a new strategy for the prevention and treatment of UC with food polyphenol. © 2024 Society of Chemical Industry.

Mitochondrial-Targeted CS@KET/P780 Nanoplatform for Site-Specific Delivery and High-Efficiency Cancer Immunotherapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a form of malignancy with limited curative options available. To improve therapeutic outcomes, it is imperative to develop novel, potent therapeutic modalities. Ketoconazole (KET) has shown excellent therapeutic efficacy against HCC by eliciting apoptosis. However, its limited water solubility hampers its application in clinical treatment. Herein, a mitochondria-targeted chemo-photodynamic nanoplatform, CS@KET/P780 NPs, is designed using a nanoprecipitation strategy by integrating a newly synthesized mitochondria-targeted photosensitizer (P780) and chemotherapeutic agent KET coated with chondroitin sulfate (CS) to amplify HCC therapy. In this nanoplatform, CS confers tumor-targeted and subsequently pH-responsive drug delivery behavior by binding to glycoprotein CD44, leading to the release of P780 and KET. Mechanistically, following laser irradiation, P780 targets and destroys mitochondrial integrity, thus inducing apoptosis through the enhancement of reactive oxygen species (ROS) buildup. Meanwhile, KET-induced apoptosis synergistically enhances the anticancer effect of P780. In addition, tumor cells undergoing apoptosis can trigger immunogenic cell death (ICD) and a longer-term antitumor response by releasing tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs), which together contribute to improved therapeutic outcomes in HCC. Taken together, CS@KET/P780 NPs improve the bioavailability of KET and exhibit excellent therapeutic efficacy against HCC by exerting chemophototherapy and antitumor immunity.

Chitosan surface-modified bovine serum albumin-oleic acid self-assembled complexes: Improving the thermal stability, controlled release and bioaccessibility of fucoxanthin

Fucoxanthin (FUCO) is a marine xanthophyll carotenoid with widespread potential physiological functions. However, poor water solubility and chemical instability limit FUCO's processing adaptability and bioavailability. In this study, chitosan surface-modified bovine serum albumin (BSA)-oleic acid (OA) self-assembled complexes were fabricated to improve the thermal stability as well as the controlled release and bioaccessibility of FUCO during gastrointestinal digestion. The results showed that glucose-grafted chitosan (GGC) could surface modify BSA-OA complexes by non-covalent affinity adhesion, resulting in a stable hydrophilic dispersion system with a polydispersity index <0.25 and a Zeta potential > −20 mV. Fourier transform infrared spectroscopy and transmission electron microscope observations revealed that GGC covered the surface of BSA-OA particles through hydrogen bonding, hydrophobic and electrostatic interactions. The GGC-BSA-OA delivery system captured FUCO with >88.00% encapsulation efficiency. Additionally, embedding FUCO in the GGC-modified BSA-OA complex improved its thermal stability. In vitro, gastrointestinal digestion simulations showed that the GGC-modified protein shell had a controlled-release effect on FUCO, which prevented acidic pH from destroying FUCO due to premature release during gastric digestion and released it during intestinal digestion. As expected, GGC-BSA-OA, an encapsulated carrier, dramatically improved the FUCO's digestive stability (retention rate >74.00%), bioaccessibility (>54.42%), and micellization rate (>70.00%) in simulated gastrointestinal digestion. These findings suggested that GGC-BSA-OA as a delivery vehicle could effectively improve FUCO's thermal processing stability and absorbability.

Enhanced solubility of methyl ester sulfonates below their Krafft points in mixed micellar solutions

HypothesisMethyl ester sulfonates (MES) show limited water solubility at lower temperatures (Krafft point). One way to increase their solubility below their Krafft points is to incorporate them in anionic surfactant micelles. The electrostatic interactions between the ionic surfactant molecules and charged micelles play an important role for the degree of MES solubility. ExperimentsThe solubility and electrolytic conductivity for binary and ternary surfactant mixtures of MES with anionic sodium alpha olefin sulfonate (AOS) and sodium lauryl ether sulfate with two ethylene oxide groups (SLES-2EO) at 5 °C during long-term storage were measured. Phase diagrams were established; a general phase separation theoretical model for their explanation was developed and checked experimentally. FindingsThe binary and ternary phase diagrams for studied surfactant mixtures include phase domains: mixed micelles; micelles + crystallites; crystallites, and molecular solution. The proposed general phase separation model for ionic surfactant mixtures is convenient for construction of such complex phase diagrams and provides information on the concentrations of all components of the complex solution and on the micellar electrostatic potential. The obtained maximal MES mole fraction of transparent micellar solutions could be of interest to increase the range of applicability of MES–surfactants.

Microfluidic fabrication of core–shell fucoxanthin nanofibers with improved environmental stability for reducing lipid accumulation in vitro

Fucoxanthin is a xanthophyll carotenoid that possesses potent antioxidant, anti-obesity, and anti-tumor properties. However, its limited solubility in water and susceptibility to degradation create challenges for its application. In this study, a microfluidic coaxial electrospinning technique was used to produce core–shell zein-gelatin nanofibers for encapsulating fucoxanthin, enhancing its bioavailability, and improving its stability. In comparison to uniaxially-loaded fucoxanthin nanofibers, the encapsulation efficiency of fucoxanthin reached 98.58 % at a core–shell flow rate ratio of 0.26:1, representing a 14.29 % improvement. The photostability of the nanofibers increased by 74.59 % after three days, UV stability increased by 38.82 % after 2 h, and temperature stability also significantly improved, demonstrating a protective effect under harsh environmental conditions (P < 0.05). Additionally, nanofibers effectively alleviated oleic acid-induced reactive oxygen species production and reduced fluorescence intensity by 54.76 %. MTT experiments indicated great biocompatibility of the nanofibers, effectively mitigating mitochondrial membrane potential polarization and lipid accumulation in HepG2 cells. Overall, the microfluidic coaxial electrospinning technique enables promising applications of fucoxanthin delivery in the food industry.

Water‐Soluble Ionic Liquid‐Containing Sulfur Polymers for Mercury Capture, Demulsification, and Antibacterial Activity

AbstractSulfur polymers, prepared by inverse vulcanization using elemental sulfur and vinylic monomers, are emerging functional materials of current research interest; however, sulfur polymers suffer from limited water solubility due to the hydrophobic nature of conventional comonomers and sulfur. Herein, the preparation of ionic liquid (IL)‐containing sulfur polymers are reported using the hydrophilic ionic liquid, 1‐allyl‐3‐vinylimidazolium chloride (AVImCl) as a comonomer. The introduction of IL significantly enhances the hydrophilicity of sulfur polymers, enabling them to dissolve in water. Benefiting from the thorough contact with aqueous mercury ions, the resultant sulfur polymer possesses high uptake capacity (436 mg g−1). After binding mercury, a coordination complex is formed and precipitated. The charged sulfur polymers gain a new application in demulsification. The polymer quickly breaks oil‐in‐water (O/W) emulsions through anion exchange between Cl− of the polymer and dodecylbenzenesulfonate (DBS−) of the surfactant. In addition, the polymer has a growth inhibitory effect against Staphylococcus aureus. The integration of IL and elemental sulfur provides a novel approach to modifying the wettability of sulfur polymers. Also, this novel water‐soluble IL‐containing sulfur polymer, with mercury capture, demulsification, and antibacterial activity, can be considered as a multifunctional material in practical water purification.

Evaluation of lupeol-chitosan nanoparticles infused cellulose acetate membranes for enhanced in-vitro anticancer and antidiabetic activities

This study utilizes the abundance of pharmacologically active compounds found in natural products and concentrates on the promising anticancer agent lupeol (LUP). The limited water solubility and bioavailability of lupeol have limited its therapeutic utility. To test their potential for treating diabetes and cancer, we synthesized lupeol@chitosan (LUP@CS) nanoparticles encapsulated in cellulose acetate (CA) membranes (LUP@CS/CA). Extensive characterization, including Scanning electron microscopy, Thermogravimetric analysis, X-ray photoelectron spectroscopy, and mechanical strength analysis, confirmed the membrane's structural integrity and drug release capacity. Notably, in vitro experiments utilizing A431 human skin cancer cells revealed remarkable anticancer activity, positioning the membrane as a potential novel therapeutic agent for the treatment of skin cancer. Inhibiting carbohydrate-digesting enzymes effectively, as evidenced by IC50 values as low as 54.56 mg/mL, the membrane also exhibited significant antidiabetic potential. These results demonstrate the multifarious potential of the membrane, which offers promise for both the treatment of skin cancer and the management of diabetes, and has significant implications for nano biological applications.

Innovative Approach to Enhance Bioavailability of Birch Bark Extracts: Novel Method of Oleogel Development Contrasted with Other Dispersed Systems.

Birch outer bark extract (BBE), containing pentacyclic triterpenes such as betulin, lupeol, and betulinic acid, is a widely recognized natural product renowned for its diverse pharmacological effects. However, its limited water solubility restricts its bioavailability. Therefore, the main objective is to enhance the bioavailability of BBE for pharmaceutical use. In this study, we aimed to develop a dispersion system utilizing a unique oleogel-producing method through the recrystallization of BBE from an ethanol solution in the oil phase. We generated an oleogel that demonstrates a notable 42-80-fold improvement in betulin and lupeol peroral bioavailability from BBE in Wistar rats, respectively. A physical paste-like BBE hydrogel developed with antisolvent precipitation showed a 16-56-fold increase in the bioavailability of betulin and lupeol from BBE in rat blood plasma, respectively. We also observed that the repeated administration of the BBE oleogel did not exhibit any toxicity at the tested dose (38.5 mg/kg betulin, 5.2 mg/kg lupeol, 1.5 mg/kg betulinic acid daily for 7 days). Betulin and betulinic acid were not detected in rat heart, liver, kidney, or brain tissues after the peroral administration of the oleogel daily for 7 days. Lupeol was found in rat heart, liver, and kidney tissues.

Biochemical and techno-functional investigation of argan press-cake proteins foreseeing food application

Argan press-cake (APC) is reported to contain a significant content of proteins, comparable to conventional sources of protein isolates, such as soybean. In this regard, the present study evaluated the biochemical and techno-functional properties of major APC proteins fractions, foreseeing food application. Albumins and globulins represented approximately 41% and 50% of total extractable proteins, respectively. Globulins were prone to aggregation, potentially by hydrophobic interactions, resulting in limited solubility in water in the range of pH 3 to pH 11. Nevertheless, the limited solubility of globulins in water at pH ≤ 9 could be improved, up to 8-fold, by pH12-shifting treatment, that is, unfolding the proteins structure at pH 12, followed by refolding at pH 9 or lower. pH12-shifted albumins and globulins presented similar surface activity in the range of pH 3 to pH 11 and were able to form and stabilize foams and emulsions. Comprehensively, both fractions reduced the interfacial tension and surface tension up to 8 mN/m and 48 mN/m, respectively, and formed stable emulsions, with a mean droplet volume diameter (d4,3) of approximately 16 μm, using rotor-stator homogenization. These results indicate that albumins and globulins extracted from argan by-products could have potential applications as techno-functional food ingredients.

Delivery of gefitinib loaded nanoparticles for effectively inhibiting prostate cancer progression.

Androgen deprivation therapy is administered to suppress the growth of prostate cancer (PCa). However, some cells continue to proliferate independent of hormones, leading to the development of castration-resistant prostate cancer (CRPC). Overexpression of the epidermal growth factor receptor (EGFR) has been observed in CRPC and is associated with an unfavorable prognosis. Gefitinib (GEF) is an EGFR inhibitor used to treat patients with CRPC. Nevertheless, some clinical studies have reported that gefitinib does not result in prostate-specific antigen (PSA) or objectively measurable CRPC reactions. This lack of response may be attributed to the limited solubility in water, high side effects, low tumor aggregation, and insufficient tumor-specific reactions of GEF. In order to tackle these obstacles, we present a practical and efficient approach to administer GEF, encompassing the utilization of biocompatible nanostructures as a vehicle for drug delivery to augment its bioaccessibility and curative potency. Despite their small particle size, poly(D,L-lactide-co-glycolide) acid nanoparticles (PLGA NPs) exhibit a high drug-loading capacity, low toxicity, biocompatibility, biodegradability, and minimal immunogenicity. The drug delivery efficiency can be improved by employing GEF@PLGA NPs, which could also enhance drug cytotoxicity and impede the advancement of prostate cancer. Moreover, through experiments in vivo, it has been verified that GEF@PLGA NPs exhibit selective accumulation in the tumor and effectively restrain tumor growth. Therefore, the GEF@PLGA NPs hold great promise for the treatment of PCa.

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization.

Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1β and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-β. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.