Poor Water Solubility Research Articles

Nanomicelles empower natamycin in treating fungal keratitis: An in vitro, ex vivo and in vivo study

Fungal infections of cornea are important causes of blindness in developing nations with tropical climate. However, the challenges associated with current treatments are responsible for poor outcome. Natamycin is the only FDA-approved antifungal drug to treat fungal keratitis, but unfortunately due to its poor water solubility, it is available as suspension. The marketed suspension (5% Natamycin) has rapid precorneal clearance, poor corneal permeability, a higher frequency of administration, and corneal irritation due to undissolved suspended drug particles. In our study, we developed clear and stable natamycin-loaded nanomicelles (1% Natcel) to overcome the above challenges. We demonstrated that 1% Natcel could permeate the cornea better than 5% suspension. The developed 1% Natcel was able to provide sustained release for up to 24 h. Further, it was found to be biocompatible and also improved the mean residence time (MRT) than 5% suspension in tears. Therefore, the developed 1% Natcel could be one of the alternative therapeutics with potential possibility in the treatment of fungal keratitis.

Facile construction of gold- and BODIPY-coordinated liposomal nanocomplexes for enhanced photothermal therapy of cancer

Photothermal therapy (PTT) has attracted extensive attention in cancer treatment because of its advantages of non-invasive and few side effects. Gold nanoparticles and boron-fluorine-dipyrrole (BODIPY) dye have been used as photothermal agents (PTAs), but they have problems such as easy aggregation, poor water solubility and low photothermal conversion efficiency. In this work, we used conventional liposomes for in situ generation of small gold nanoparticles and sequentially loading BODIPY to overcome the drawbacks of the two PTAs and simultaneously realize enhanced PTT. Gold- and BODIPY-coordinated liposomal nanocomplexes LAB with small gold nanoparticles adsorbed on the surface and BODIPY entrapped inside showed uniform size of about 100 nm with good stability. LAB demonstrated laser-responsive drug release property, good cellular uptake efficiency and tumor accumulation ability. After laser irradiation, LAB can exert enhanced PTT in cancer cell lines by reducing mitochondrial membrane potential and increase intracellular reactive oxygen species level to promote cell apoptosis. In tumor-bearing mice, LAB showed fantastic tumor inhibition effect with good biosafety. This work provides a convenient method to develop PTA combinations for enhanced PTT, which could lay the foundation for the green construction of new PTAs for PTT by employing clinically used formulations and PTAs.

Homo-Dyad with Outer Hydration Layer Approach for Developing NIR-II Chromophore of High Stability and Water-Solubility as Injectable and Sprayable Optical Probe.

Dyes with extended conjugate structures are the focus of extensive design and synthesis efforts, aiming to confer unique and improved optical and electronic properties. Such advancements render these dyes applicable across a wide spectrum of uses, ranging from second-window near-infrared (NIR-II) bioimaging to organic photovoltaics. Nevertheless, the inherent benefits of long conjugation are often accompanied by persistent challenges like aggregation, fluorescence quenching, absorption blueshift, and low stability and poor water solubility. Herein, a unique structural design strategy termed "homo-dyad with outer hydration layer" is introduced to address these inherent problems, tailored for the development of imaging probes exhibiting long absorption/emission wavelengths. This approach involves bringing two heptamethine cyanines together through a flexible linker, forming a homo-dyad structure, while strategically attaching four polyethylene glycol (PEG9) chains to the terminal heterocycles. This approach imparts excellent water solubility, biocompatibility, and enhanced chemical, photo-, and spectral stability for the dyes. Utilizing this strategy, a biomarker-activatable probe (HD-FL-4PEG9-N) for NIR-II fluorescent and 3D multispectral optoacoustic tomography imaging is developed, and its effectiveness in disease visualization. It can not only serve as an injectable probe for acute kidney injury imaging due to its high water solubility, but also a sprayable probe for imaging bacterial-infected wounds.

Wondrous Yellow Molecule: Are Hydrogels a Successful Strategy to Overcome the Limitations of Curcumin?

Curcumin is a natural compound with a great pharmaceutical potential that involves anticancer, anti-inflammatory, antioxidant, and neuroprotective activity. Unfortunately, its low bioavailability, instability, and poor water solubility significantly deteriorate its clinical use. Many attempts have been made to overcome this issue, and encapsulating curcumin in a hydrogel matrix may improve those properties. Hydrogel formulation is used in many drug delivery forms, including classic types and novel forms such as self-assembly systems or responsive to external factors. Reviewed studies confirmed better properties of hydrogel-stabilized curcumin in comparison to pure compound. The main enhanced characteristics were chemical stability, bioavailability, and water solubility, which enabled these systems to be tested for various diseases. These formulations were evaluated for wound healing properties, effectiveness in treating skin diseases, and anticancer and regenerative activity. Hydrogel formulation significantly improved biopharmaceutical properties, opening the opportunity to finally see curcumin as a clinically approved substance and unravel its therapeutic potential.

Optimizing clozapine-loaded nanostructured lipid carriers through central composite design for enhance bioavailability in antipsychotic therapy

Clozapine (CLZ), a tricyclic dibenzodiazepine antipsychotic drug employed for the treatment of Schizophrenia. However, CLZ's significant first-pass effect, poor water solubility, and low oral bioavailability (27%) limit its potential for therapeutic use. The present investigation aimed to prepare CLZ-loaded nanostructured lipid carriers (NLCs) to improve its solubility, bioavailability, and therapeutic efficacy. The NLCs were prepared using an ultrasonic probe sonication technique using selected solid lipids (Gelucire 44/14), liquid lipids (Labrafil M 1944), and surfactants (Monoemul 80). A central composite design approach was adopted to optimize the NLCs. The optimized CLZ-loaded NLCs were evaluated in terms of particle size, zeta potential, surface morphology, crystallinity, drug loading, and in-vitro CLZ release studies. The optimized CLZ-loaded NLCs showed a particle size, zeta potential, and entrapment efficiency of 115.1 ± 2.48 nm, −17 mV and 96.74 ±1.82%, respectively. The morphology revealed the coarsely spherical shape of NLCs. Fourier transform infrared spectroscopy indicated the physical interaction between the CLZ and lipids rather than chemical interaction. The results of powder X-ray diffraction and differential scanning calorimetry showed the conversion of crystalline to amorphous form of CLZ and distributed molecular level in lipid matrix. In the in-vitro release study, pure CLZ showed 14±1.86% release, whereas CLZ-loaded NLC showed initial burst release (20.0±0.56%) followed by sustained release (69.0±1.03%) up to 24 hours. Collectively, results revealed that the developed novel CLZ-loaded NLCs could be a potential formulation to improve efficacy by increasing solubility and prolonging CLZ release and bioavailability with enhanced patient compliance and reduced side effects.

Intranasal Delivery of Curcumin Nanoparticles Improves Neuroinflammation and Neurological Deficits in Mice with Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) represents one of the most severe subtypes of stroke. Due to the complexity of the brain injury mechanisms following ICH, there are currently no effective treatments to significantly improve patient functional outcomes. Curcumin, as a potential therapeutic agent for ICH, is limited by its poor water solubility and oral bioavailability. In this study, mPEG-PCL is used to encapsulate curcumin, forming curcumin nanoparticles, and utilized the intranasal administration route to directly deliver curcumin nanoparticles from the nasal cavity to the brain. By inhibiting pro-inflammatory neuroinflammation of microglia following ICH in mice, reprogramming pro-inflammatory microglia toward an anti-inflammatory function, and consequently reducing neuronal inflammatory death and hematoma volume, this approach improved blood-brain barrier damage in ICH mice and promoted the recovery of neurological function post-stroke. This study offers a promising therapeutic strategy for ICH to mediate neuroinflammatory microenvironments.

Coreactant-free aggregation-induced electrochemiluminescence system based on the novel zinc-luminol metal-organic gel for ultrasensitive detection of PiRNA-823

Aggregation-induced electrochemiluminescence (AIECL) technology has aroused widespread interest due to the significant improve in ECL response by solving the problems of aggregation-caused quenching and poor water solubility of the luminophore. However, the existing AIECL emitters still suffer from low ECL efficiency, additional coreactants and complex synthesis steps, which greatly limit their applications. Herein, luminol, as a kind of AIE molecule, was assembled with Zn2+ nodes to obtain a novel microflower-like Zinc-luminol metal-organic gel (Zn-MOG) by one-step method. In the light of the strong affinity of N atoms in luminol ligand to Zn2+, Zn-MOG with vigorous viscosity and stability can be formed immediately after vortex oscillation, overcoming the main difficulties of the complicated synthesis steps and poor film-forming performance encountered in current AIECL materials. Impressively, an AIECL resonance energy transfer (RET) biosensor was constructed using Zn-MOG as a donor and Alexa Fluor 430 as an acceptor in combination with DNA-Fuel-driven target recycling amplification for the ultrasensitive detection of PiRNA-823. The fabricated biosensor exhibited a wide linear relationship in the range of 100 aM to 100 pM and a detection limit as low as 60.0 aM. This work is the first to realize the construction of ECL emitters using the AIE effect of luminol, which provides inspiration for the design of AIECL systems without adding coreactants.

Membrane-Fusing Vehicles for Re-Sensitizing Transporter-Mediated Multiple-Drug Resistance in Cancer

Reversing the multiple drug resistance (MDR) arising from the overexpression of the efflux transporters often fails mainly due to the high toxicity or the poor water solubility of the inhibitors of these transporters. Here, we demonstrate the delivery of an inhibitor targeting three ABC transporters (ABCB1, ABCC1 and ABCG2) directly to the cell membrane using membrane-fusing vehicles (MFVs). Three different transfected MDCK II cell lines, along with parental cells, were used to investigate the inhibitory effect of cyclosporine A (CsA) in solution versus direct delivery to the cell membrane. CsA-loaded MFVs successfully reversed MDR for all three investigated efflux transporters at significantly lower concentrations compared with CsA in solution. Results showed a 15-fold decrease in the IC50 value for ABCB1, a 7-fold decrease for ABCC1 and an 11-fold decrease for ABCG2. We observed binding site specificity for ABCB1 and ABCG2 transporters. Lower concentrations of empty MFVs along with CsA contribute to the inhibition of Hoechst 33342 efflux. However, higher concentrations of CsA along with the high amount of MFVs activated transport via the H-binding site. This supports the conclusion that MFVs can be useful beyond their role as delivery systems and also help to elucidate differences between these transporters and their binding sites.

Computer-aided design and optimization of estradiol valerate nanoemulsion-loaded core-shell microneedle patches for controlled release transdermal drug delivery

Estradiol valerate (E2V) is a hormone utilized for estrogen replacement therapy. Nonetheless, its application in pharmaceutical formulations has been limited due to its poor solubility in water and suboptimal efficacy for transdermal drug delivery. Hence, the combination of nanoemulsions (NEs) with core-shell dissolving microneedles (CS-dMNs), which encase the drug, represents a promising approach to enhance transdermal drug delivery while ensuring controlled release. This study aimed to develop E2V-NE-loaded CS-dMNs for achieving controlled transdermal release of E2V. The E2V-NEs were formulated and evaluated for parameters including droplet size, polydispersity index (PDI), and zeta potential. Subsequently, these E2V-NEs were integrated into the core of CS-dMNs. The physical and mechanical properties of E2V-NE-loaded CS-dMNs were evaluated, along with parameters such as detachment time, drug content, in vitro and in vivo skin permeation, and safety. The results indicated that E2V-NE-loaded CS-dMNs exhibited favorable physical and mechanical characteristics, enabling easy self-administration with patch detachment after 30 min, while ensuring controlled drug release from the core of dMNs. The E2V content in CS-dMNs was determined to be 0.76 ± 0.15 mg/patch. Furthermore, in vitro and in vivo skin permeation studies demonstrated a synergistic effect between NEs and MNs, achieving therapeutic drug levels sustained over a week (368.54 ± 67.93 μg/mL in in vitro and 697.45 ± 270.10 pg/mL in in vivo), with no indications of infection and complete skin healing observed within 8 h. Consequently, E2V-NE-loaded CS-dMNs present a promising alternative for achieving sustained and controlled hormone levels conveniently.

Nanostructured lipid carrier loaded with Zingiber officinale oil to enhance transdermal bioactive delivery for topical formulation

This study reported on the enhancement of Zingiber officinale (Z. officinale) oil delivery, a bioactive with poor water solubility, by incorporating it into nanostructured lipid carriers (NLC) for transdermal bioactive delivery in topical formulations using the ultrasonication technique with a D–optimal mixture design approach. The independent factors in the process included the percentage of Z. officinale oil, solid lipid (glyceryl monostearate (GMS)), and liquid lipid (virgin coconut oil (VCO)). The study characterized the NLC– Z. officinale oil formulation based on particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) as the dependent variables. Besides, Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy with Attenuated Total Reflection (FTIR–ATR), and Differential Scanning Calorimetry (DSC) were also employed. The optimized NLC–Z. officinale oil formulation, comprising 0.36 % Z. officinale oil, 0.14 % solid lipid (GMS), and 0.50 % liquid lipid (VCO). The study's results demonstrated that the finely tuned NLC– Z. officinale oil formulation, with an average diameter of 90.71 ± 9.48 nm, a PDI of 0.147 ± 0.01, a ZP of –45.7 ± 0.67 mV, and an EE of 88.80 ± 11.18 %, exhibited a controlled and sustained release profile following the Korsmeyer–Peppas model. The in vitro penetration studies on excised Sprague–Dawley rat skin and Strat–M® showcased the heightened penetration flux of NLC–Z. officinale oil compared to Z. officinale oil. Furthermore, in vivo distribution studies in female Sprague–Dawley rats underscored the deep penetration of NLCs into the dermal layer after 12 h of application. Notably, a 3–hour treatment with NLC–Z. officinale oil triggered the release of free fatty acids (FFA). The 90 days storage stability study revealed no significant changes in NLC– Z. officinale oil concerning PS and PDI, affirming its stability over time. These findings illuminated the potential applications of NLC– Z. officinale oil as a robust transdermal bioactive delivery system for Z. officinale oil. This underscored its significance in pharmaceutical formulations, providing a novel avenue for therapeutic purposes.

Fabrication and in vitro/vivo evaluation of quercetin nanocrystals stabilized by glycyrrhizic acid for liver targeted drug delivery

The purpose of this study was to design novel drug nanocrystals (NCs) stabilized by glycyrrhizic acid (GL) for achieving liver targeted drug delivery due to the presence of GL receptor in the hepatocytes. Quercetin (QT) exhibits good pharmacological activities for the treatment of liver diseases, including liver steatosis, fatty hepatitis, liver fibrosis, and liver cancer. It was selected as a model drug owing to its poor water solubility. QT NCs stabilized by GL (QT-NCs/GL) were fabricated by wet media milling technique and systemically evaluated. QT-NCs stabilized by poloxamer 188 (QT-NCs/P188) were prepared as a reference for comparison of in vitro and in vivo performance with QT-NCs/GL. QT-NCs/GL and QT-NCs/P188 with similar particle size around 130 nm were successfully fabricated by wet media milling technique. Both of QT-NCs/GL and QT-NCs/P188 showed irregular particles and short rods under SEM. XRPD revealed that QT-NCs/GL and QT-NCs/P188 remained in crystalline state with reduced crystallinity. QT-NCs/GL and QT-NCs/P188 exhibited significant solubility increase and drug release improvement of QT as compared to raw QT. No significant difference for the plasma concentration–time curves and pharmacokinetic parameters of QT were found following intravenous administration of QT-NCs/GL and QT-NCs/P188. However, a significantly higher liver distribution of QT following intravenous administration of QT-NCs/GL was observed in comparison to QT-NCs/P188, indicating QT-NCs stabilized by GL could achieve liver targeted delivery of QT. It could be concluded that GL used as stabilizer of QT NCs have a great potential for liver targeted drug delivery.

Development of zein-based complexes and conjugates with enhanced surface hydrophilicity: Structure, emulsifying, foaming, and antioxidant properties

Corn zein is an abundant and inexpensive source of plant proteins. However, it is a strongly hydrophobic molecule with poor water solubility, which limits its range of applications in the food and other industries. In this study, zein-EGCG-alginate ternary conjugates were prepared using an alkaline treatment combined with the Maillard reaction. The nature of the conjugates formed was characterized using a range of analytical methods, including SDS-PAGE, dynamic light scattering, particle electrophoresis, spectroscopy, calorimetry, and electron microscopy. Scanning and transmission electron microscopy showed that the particles in the dispersion of ternary complexes were larger and more irregularly shaped than those in the original protein dispersion. Spectroscopic analyses indicated alterations in the structure of the proteins caused by both the alkaline and Maillard reaction treatments. Ternary conjugates (zein-EGCG-alginate) had better emulsification and foaming properties than single proteins (zein) or binary conjugates (zein-EGCG). Moreover, the surface hydrophobicity of the ternary complexes was lower, while their thermal stability and antioxidant activity were higher. For instance, the DPPH and ABTS free radical scavenging activity of the ternary conjugates were enhanced to around 67% and 89%, respectively. The alkaline-Maillard treatment also greatly improved the water dispersibility of zein, reaching a solubility level close to 60%. This study may broaden the range of applications of zein as a functional ingredient in the food and other sectors.

CBC-1 as a Cynanbungeigenin C derivative inhibits the growth of colorectal cancer through targeting Hedgehog pathway component GLI 1

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers that results in death in worldwide. The Hedgehog (HH) signalling pathway regulates the initiation and progression of CRC. Inhibiting the HH pathway has been presented as a potential treatment strategy in recent years. Cynanbungeigenin C (CBC) is a new type of C21 steroid that has been previously reported for the treatment of medulloblastoma. However, its further investigation was limited by its poor water solubility. In this study, six new CBC derivatives were synthesized through the structural modification of CBC, and four of them showed better water solubility than CBC. Moreover, their antiproliferative activities on CRC were evaluated. It was found that CBC-1 presented the best inhibitory effect on three types of CRC cell lines, and this effect was superior to that of CBC. Mechanistically, CBC-1 inhibited the proliferation of CRC cells through regulation of mRNA and proteins of the HH pathway according to qRT–PCR and Western blotting analysis. Furthermore, Cellular Thermal Shift Assay results indicated that CBC-1 regulated this signalling pathway by targeting glioma‑associated oncogene (GLI 1).In addition, cell apoptosis was induced increasingly by transfection with GLI 1 siRNA or treatment with CBC-1 to downregulate GLI 1. Last, the in vivo results demonstrated that CBC-1 significantly reduced tumour size and downregulated GLI 1 in CRC. Therefore, this study suggests that CBC-1, a new GLI 1 inhibitor derived from natural products, may be developed as a potential antitumour candidate for CRC treatment.

Preparation of self-standing ultra-thin three-dimensional covalent organic frameworks by interfacial polymerization for dye separation

Preparation of self-standing ultra-thin three-dimensional covalent organic frameworks by interfacial polymerization for dye separation

Resveratrol nanocrystals based dissolving microneedles with highly efficient for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common immune disease characterized mainly by erosive arthritis with extensive clinical sequelae. Resveratrol (Res) has pharmacological effects in the treatment of RA, but it has not been widely used in the clinic due to its poor water solubility and low bioavailability. In this study, a drug delivery system (Res-NC MNs) of dissolved microneedles (MNs) loaded with Res nanocrystals (NC) was designed for the treatment of RA. Res-NC MNs can improve the drawbacks of long-term oral drug delivery with toxic side effects and low compliance associated with intra-articular drug delivery. In this study, Res-NC was prepared by media milling and loaded into soluble microneedles prepared from hyaluronic acid (HA) by vacuum casting for the treatment of RA. HA has high mechanical strength and can penetrate the cuticle layer of the skin for effective drug delivery. In in vivo pharmacodynamic experiments, Res-NC MNs achieved better therapeutic efficacy in the treatment of RA compared with oral Res. These findings suggest that Res-NC MNs may be an effective and promising drug delivery strategy for the treatment of RA.

Redox-Responsive Gold Nanoparticles Coated with Hyaluronic Acid and Folic Acid for Application in Targeting Anticancer Therapy.

Methotrexate (MTX) has poor water solubility and low bioavailability, and cancer cells can become resistant to it, which limits its safe delivery to tumor sites and reduces its clinical efficacy. Herein, we developed novel redox-responsive hybrid nanoparticles (NPs) from hyaluronic acid (HA) and 3-mercaptopropionic acid (MPA)-coated gold NPs (gold@MPA NPs), which were further conjugated with folic acid (FA). The design of FA-HA-ss-gold NPs aimed at enhancing cellular uptake specifically in cancer cells using an active FA/HA dual targeting strategy for enhanced tumor eradication. MTX was successfully encapsulated into FA-HA-ss-gold NPs, with drug encapsulation efficiency (EE) as high as >98.7%. The physicochemical properties of the NPs were investigated in terms of size, surface charges, wavelength reflectance, and chemical bonds. MTX was released in a sustained manner in glutathione (GSH). The cellular uptake experiments showed effective uptake of FA-HA-ss-gold over HA-ss-gold NPs in the deep tumor. Moreover, the release studies provided strong evidence that FA-HA-ss-gold NPs serve as GSH-responsive carriers. In vitro, anti-tumor activity tests showed that FA-HA-ss-gold/MTX NPs exhibited significantly higher cytotoxic activity against both human cervical cancer (HeLa) cells and breast cancer (BT-20) cells compared to gold only and HA-ss-gold/MTX NPs while being safe for human embryonic kidney (HEK-293) cells. Therefore, this present study suggests that FA-HA-ss-gold NPs are promising active targeting hybrid nanocarriers that are stable, controllable, biocompatible, biodegradable, and with enhanced cancer cell targetability for the safe delivery of hydrophobic anticancer drugs.

Co-assembly of quinoa protein isolate and shellac as nano-vehicles for naringenin: Characterization, formation mechanism, release behavior and cellular uptake

Naringenin (Nar) is a natural flavonoid with diverse health-promoting benefits. However, the bioavailability of Nar is significantly restricted due to its poor water-solubility, instability under physiological conditions, and limited absorption profile. In this study, a shellac-quinoa protein isolate (QPI) binary nanocomplex (SQP) was fabricated using the pH-shifting method for effectively delivering Nar. Isothermal titration calorimetry (ITC) and analysis of inner interactive forces revealed that the complexation between QPI and shellac was primarily driven by electrostatic and hydrophobic forces. Subsequently, Nar was successfully encapsulated within the stable and uniform SQP nanocomplex (Nar@SQP), achieving a high encapsulation capacity (94.52 % encapsulation efficiency and 14.68 % loading capacity). Meanwhile, the Nar@SQP nanoparticle exhibited excellent stability against pH, ionic strength, and long-term storage. Moreover, it also demonstrated sustained and slow-release characteristics during simulated gastrointestinal digestion. Compared to free Nar, the safe Nar@SQP nanoparticle effectively facilitated the cellular uptake of encapsulated Nar by Caco-2 cells, suggesting that Nar@SQP has a good potential to improve the bioavailability of Nar. Hence, these findings indicated that the developed Nar@SQP nanoparticle might hold significant promise as a nano-delivery system for hydrophobic bioactive nutrients, like Nar.

Beyond Nanoparticle-Based Intracellular Drug Delivery: Cytosol/Organelle-Targeted Drug Release and Therapeutic Synergism.

Nanoparticle (NP)-based drug delivery systems are conceived to solve poor water-solubility and chemical/physical instability, and their purpose expanded to target specific sites for maximizing therapeutic effects and minimizing unwanted events of payloads. Targeted sites are also narrowed from organs/tissues and cells to cytosol/organelles. Beyond specific site targeting, the particular release of payloads at the target sites is growing in importance. This review overviews various issues and their general strategies during multiple steps, from the preparation of drug-loaded NPs to their drug release at the target cytosol/organelles. In particular, this review focuses on current strategies for "first" delivery and "later" release of drugs to the cytosol or organelles of interest using specific stimuli in the target sites. Recognizing or distinguishing the presence/absence of stimuli or their differences in concentration/level/activity in one place from those in another is applied to stimuli-triggered release via bond cleavage or nanostructural transition. In addition, future directions on understanding the intracellular balance of stimuli and their counter-stimuli are demonstrated to synergize the therapeutic effects of payloads released from stimuli-sensitive NPs.

Oral Curcumin–Thioketal–Inulin Conjugate Micelles against Radiation–Induced Enteritis

Radiation–induced enteritis is an unavoidable complication associated with pelvic tumor radiotherapy, significantly influencing the prognosis of cancer patients. The limited availability of commercial gastrointestinal radioprotectors in clinical settings poses a substantial challenge in preventing radiation enteritis. Despite the inherent radioprotective characteristics of Cur in vitro, its poor solubility in water, instability, and low bioavailability lead to inferior therapeutic effects in vivo. Herein, we developed novel ROS-responsive micelles (CTI) from inulin and curcumin, aimed at mitigating radiation enteritis. CTI micelles had excellent solubility and stability. Importantly, CTI improved the cytotoxicity and bioavailability of curcumin, thereby showing enhanced effectiveness in neutralizing ROS induced by radiation, safeguarding against DNA damage, and reducing radiation-induced cellular mortality. Moreover, in a radiation enteritis mice model, CTI not only alleviated severe radiation-induced intestinal injury but also improved redox-related indicators and reduced inflammatory cytokine expression. Furthermore, CTI effectively increased gut microbiota abundance and maintained gut homeostasis. In conclusion, CTI could be a promising candidate for the clinical management of radiation enteritis. Our study provides a new perspective for radioprotection using natural antioxidants.

Phytochemicals against Osteoarthritis by Inhibiting Apoptosis.

Osteoarthritis (OA) is a chronic joint disease that causes pathological changes in articular cartilage, synovial membrane, or subchondral bone. Conventional treatments for OA include surgical and non-surgical methods. Surgical treatment is suitable for patients in the terminal stage of OA. It is often the last choice because of the associated risks and high cost. Medication of OA mainly includes non-steroidal anti-inflammatory drugs, analgesics, hyaluronic acid, and cortico-steroid anti-inflammatory drugs. However, these drugs often have severe side effects and cannot meet the needs of patients. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Apoptosis is programmed cell death, which is a kind of physiologic cell suicide determined by heredity and conserved by evolution. Inhibition of apoptosis-related pathways has been found to prevent and treat a variety of diseases. Excessive apoptosis can destroy cartilage homeostasis and aggravate the pathological process of OA. Therefore, inhibition of apoptosis-related factors or signaling pathways has become an effective means to treat OA. Phytochemicals are active ingredients from plants, and it has been found that phytochemicals can play an important role in the prevention and treatment of OA by inhibiting apoptosis. We summarize preclinical and clinical studies of phytochemicals for the treatment of OA by inhibiting apoptosis. The results show that phytochemicals can treat OA by targeting apoptosis-related pathways. On the basis of improving some phytochemicals with low bioavailability, poor water solubility, and high toxicity by nanotechnology-based drug delivery systems, and at the same time undergoing strict clinical and pharmacological tests, phytochemicals can be used as a potential therapeutic drug for OA and may be applied in clinical settings.