Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
Nanotechnology has revolutionized drug delivery,particularly through nanoformulations of phytoconstituents,enhancing their therapeutic potential.Despite their broad bioactivities,plant-based compounds often suffer fro...Nanotechnology has revolutionized drug delivery,particularly through nanoformulations of phytoconstituents,enhancing their therapeutic potential.Despite their broad bioactivities,plant-based compounds often suffer from poor bioavailability and stability.Nanoformulations address these limitations by improving solubility,targeted delivery,and controlled release.This approach opens new possibilities for treating chronic diseases like cancer,diabetes,and neurodegenerative disorders.This review aims to examine recent advancements in nanotechnology-based formulation strategies designed to enhance the delivery,stability,and therapeutic efficacy of phytochemicals and also discusses regulatory issues,safety concerns,scalability,and cost-effectiveness.Emphasis was placed on nanoformulation techniques employed for key phytoconstituents such as curcumin,resveratrol,epigallocatechin gallate,and quercetin.The most commonly employed nanocarriers included polymeric nanoparticles,solid lipid nanoparticles,and liposomes.These formulations significantly improved the solubility,stability,and controlled release profiles of phytochemicals.In vitro and in vivo studies demonstrated enhanced anti-inflammatory,anticancer,and antioxidant activities.Moreover,surface-modified and targeted nanoparticles showed promise in increasing site-specific targeting and enhancing bioavailability of the encapsulated compounds.Nanoformulations present a promising strategy for overcoming the pharmacokinetic limitations of phytochemicals.Despite encouraging preclinical results,further studies are needed to address issues related to long-term safety,clinical efficacy,and regulatory approval for successful clinical translation.展开更多
Mesoporous silica nanoparticles(MsNs)are thought to be an attractive drug delivery material because of their advantages including high specific surface area,tunable pore size and morphology,easy sur-face modification ...Mesoporous silica nanoparticles(MsNs)are thought to be an attractive drug delivery material because of their advantages including high specific surface area,tunable pore size and morphology,easy sur-face modification and good biocompatibility.However,as a result of the poor biodegradability of MsNs,their biomedical applications are limited.To break the bottleneck of limited biomedical applications of MSNs,more and more researchers tend to design biodegradable MSNs(b-MSNs)nanosystems to obtain biodegradable as well as safe and reliable drug delivery carriers.In this review,we focused on sum-marizing strategies to improve the degradability of MsNs and innovatively proposed a series of advan-tages of b-MsNs,including controlled cargo release behavior,multifunctional frameworks,nano-catalysis,bio-imaging capabilities and enhanced therapeutic effects.Based on these advantages,we have inno-vatively summarized the applications of b-MsNs for enhanced tumor theranostics,including enhanced chemotherapy,delivery of nanosensitizers,gas molecules and biomacromolecules,initiation of immune response,synergistic therapies and image-guided tumor diagnostics.Finally,the challenges and further clinical translation potential of nanosystems based on b-MsNs are fully discussed and prospected.We believe that such b-MsNs delivery carriers will provide a timely reference for further applications in tu-mor theranostics.展开更多
Mimicking the hierarchical structure of the skin is one of the most important strategies in skin tissue engineering.Monolayer wound dressings are usually not able to provide several functions at the same time and cann...Mimicking the hierarchical structure of the skin is one of the most important strategies in skin tissue engineering.Monolayer wound dressings are usually not able to provide several functions at the same time and cannot meet all clinical needs.In order to maximize therapeutic efficiency,herein,we fabricated a Tri-layer wound dressing,where the middle layer was fabricated via 3D-printing and composed of alginate,tragacanth and zinc oxide nanoparticles(ZnO NPs).Both upper and bottom layers were constructed using electrospinning technique;the upper layer was made of hydrophobic polycaprolactone to mimic epidermis,while the bottom layer consisted of Soluplus■ and insulin-like growth factor-1(IGF-1)to promote cell behavior.Swelling,water vapor permeability and tensile properties of the dressings were evaluated and the Tri-layer dressing exhibited impressive antibacterial activity and cell stimulation following by the release of ZnO NPs and IGF-1.Additionally,the Tri-layer dressing led to faster healing of full-thicknesswound in ratmodel compared to monolayer and Bilayer dressings.Overall,the evidence confirmed that the Trilayer wound dressing is extremely effective for full-thickness wound healing.展开更多
Intratumoral bacteria have been proven to be widely exist in tumors,different tumors of different systems have different types of characteristic bacteria.Intratumoral bacteria will become a new and important biomarker...Intratumoral bacteria have been proven to be widely exist in tumors,different tumors of different systems have different types of characteristic bacteria.Intratumoral bacteria will become a new and important biomarker in the full cycle of tumor development.This article emphasizes the key role of intratumoral bacteria in the occurrence and progress of tumors,including promoting tumor development,accelerating tumor metastasis and promoting tumor cell resistance.In addition,this article also summarizes the application of intratumoral bacteria in tumor diagnosis and prognosis.Especially,this article outlines the treatment strategies of intratumoral bacteria,including non-nanodelivery therapy strategies and nanodelivery therapy strategies,such as antibiotic,macromolecular,inflammatory factor inhibitors,near-infrared-photothermal therapy,inorganic antibacterial agents,reactive species and microbes therapy,in these strategies,nano delivery system provides a promising treatment that solves the problem of drug resistance,reducing toxicity and improving patient compliance.This article is hoped to guide future research on intratumoral bacteria on tumors.展开更多
Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and th...Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.展开更多
Background:Luliconazole is an imidazole antifungal drug mainly used to treat dermatophytic infections including tinea pedis,tinea cruris,and tinea corporis.Objective:The purpose of this research was to synthesize a tr...Background:Luliconazole is an imidazole antifungal drug mainly used to treat dermatophytic infections including tinea pedis,tinea cruris,and tinea corporis.Objective:The purpose of this research was to synthesize a transferosomal gel incorporating luliconazole for external applications.Materials and methods:The preparation method employed thin film hydration to prepare transferosomes loaded with luliconazole with lecithin and tween 80 at different concentrations.The transferosomes formed were characterized in terms of particle size and entrapment efficiency.Finally,the prepared transferosomes were applied in a carbopol gel base and characterized for drug content,pH,spreadability,viscosity,in vitro release profile,and antifungal studies.Results:The synthesized luliconazole transferosomes had high entrapment efficiency of 74.45%,and 92.75%,with particle size ranging between 60 and 200 nm.The shape of the transferosomes was established using scanning electron microscopy;the results depicted spherical-shaped vesicles.The in vitro release study also suggested that the entrapment efficiency influences in vitro release where there is a negative relationship between the two.The gel formulation revealed a good antifungal effect.Conclusion:The luliconazole transferosomal gel exhibited a sustained release profile of the drug and thus may lessen the number of applications required,thereby enhancing patient compliance.展开更多
Objective:Prostate cancer(PCA)is the second most widespread cancer among men globally,with a rising mortality rate.Enzyme-responsive lipid nanoparticles(ERLNs)are promising vectors for the selective delivery of antica...Objective:Prostate cancer(PCA)is the second most widespread cancer among men globally,with a rising mortality rate.Enzyme-responsive lipid nanoparticles(ERLNs)are promising vectors for the selective delivery of anticancer agents to tumor cells.The goal of this study is to fabricate ERLNs for dual delivery of gefitinib(GF)and simvastatin(SV)to PCA cells.Methods:ERLNs loaded with GF and SV(ERLNGFSV)were assembled using bottomup and top-down techniques.Subsequently,these ERLN cargoes were coated with triacylglycerol,and phospholipids and capped with chitosan(CS).The ERLNGFSV,and CS engineered ERLNGFSV(CERLNGFSV)formulations were characterized for particle size(PS),zeta potential(ZP),and polydispersity index(PDI).The biocompatibility,and cytotoxicity of the plain and GF plus SV-loaded ERLN cargoes were assessed using erythrocytes and PC-3 cell line.Additionally,molecular docking simulations(MDS)were conducted to examine the influence of GF and SV on succinate dehydrogenase(SDH),glutathione peroxidase-4(GPX-4),and 5α-reductase(5α-RD).Results:These results showed that plain,ERLNGFSV,and CERLNGFSV cargoes have a nanoscale size and homogeneous appearance.Moreover,ERLNGFSV and CERLNGFSV were biocompatible,with no detrimental effects on erythrocytes.Treatment with GF,SV,GF plus SV,ERLNGFSV,and CERLNGFSV significantly reduced the viability of PC-3 cells compared to control cells.Particularly,the blend of GF and SV,as well as ERLNGFSV and CERLNGFSV augmented PC-3 cell death.Also,treating PC-3 cells with free drugs,their combination,ERLNGFSV,and CERLNGFSV formulations elevated the percentage of apoptotic cells.MDS studies demonstrated that GF and SV interact with the active sites of SDH,GPX-4,and 5α-reductase.Conclusions:This study concludes that SVGF combination and ERLNs loading induce particular delivery,and synergism on PC-3 death through action on multiple pathways involved in cell proliferation,and apoptosis,besides the interaction with SDH,GPX-4,and 5α-RD.Therefore,GFSV-loaded ERLN cargoes are a promising strategy for PCA treatment.In vivo studies are necessary to confirm these findings for clinical applications.展开更多
Photodynamic therapy(PDT)not only directly eradicates tumor cells but also boosts immunogenicity,promoting antigen presentation and immune cell infiltration.However,the robust antioxidant defense mechanisms within tum...Photodynamic therapy(PDT)not only directly eradicates tumor cells but also boosts immunogenicity,promoting antigen presentation and immune cell infiltration.However,the robust antioxidant defense mechanisms within tumor cells significantly weaken the efficacy of photodynamic immunotherapy.Herein,a supramolecular hybrid nanoassembly is constructed by exploring the synergistic effects of the photodynamic photosensitizer(pyropheophorbide a,PPa)and the ferroptosis inducer(erastin).The erastinmediated inhibition of system X_(c)−significantly downregulates glutathione(GSH)expression,amplifying intracellular oxidative stress,leading to pronounced cell apoptosis,and promoting the release of damageassociated molecular patterns(DAMPs).Additionally,the precise cooperation of PPa and erastin enhances ferroptosis efficiency,exacerbating the accumulation of lipid peroxides(LPOs).Ultimately,LPOs serve as a“find me”signal,while DMAPs act as an“eat me”signal,collectively promoting dendritic cell maturation,enhancing infiltration of the cytotoxic T lymphocytes,and eliciting a robust immune response.This study opens new horizons for enhancing tumor immunotherapy through simultaneous ferroptosis-PDT.展开更多
Background:Hepatocellular carcinoma(HCC)is a health problem due to multi-drug resistance(MDR).Codelivery of multiple oncotherapy in one cargo as chimeric cancer therapy(CCT)is suggested as a solution for MDR.This stud...Background:Hepatocellular carcinoma(HCC)is a health problem due to multi-drug resistance(MDR).Codelivery of multiple oncotherapy in one cargo as chimeric cancer therapy(CCT)is suggested as a solution for MDR.This study aims to engineer chitosan-coated nanostructure lipid carriers(NLCs)loaded with gefitinib(GF)and simvastatin(SV)as CCT for HCC.Methods:Both GF and SV-loaded nanostructure lipids carriers(GFSVNLC)and chitosan-capped GF and SV-loaded nanostructure lipids carriers(CGFSVNLC)formulations were assembled by topdown techniques.Moreover,particle size(PS),zeta potential(ZP),and polydispersity index(PDI)were measured by Zetasizer.The biosafety of GFSVNLC preparations was investigated by using erythrocytes as a biological model.The cytotoxic,and apoptotic effects of the prepared GFSVNLCs were investigated using HepG2 cell lines as a substitute model for HCC.The effect of GF,SV,and NLC composition on JNK3,HDAC6,and telomerase was studied using molecular docking simulation(MDS).Results:The present results revealed that the obtained GFSVNLC and CGFSVNLC have nanosized and consistent,CS coating shifts anionic ZP of GFSVNLC into CGFSVNLC with cationic ZP.Moreover,both formulations are biocompatible as indicated by their gentle effect on erythrocyte hemolysis.The treatment of HepG2 cells with GFSVNLC,and CGFSVNLC induced marked cell death compared to other groups with a decrease of IC50.Equally,the percentage of the apoptotic HepG2 cells was increased upon treatment of the cells with GFSV,GFSVNLC,and CGFSVNLC compared to the control group.Additionally,GF,SV,stearic acid(SA),and oleic acid(OA)modulate the activity of JNK3,HDAC6,and telomerase.Conclusions:This study suggests CGFSVNLC achieves codelivery,selective targeting,and enhancing the synergistic effect of GF and SV for inducing HepG2 cell death.Mechanistically,CGFSVNLC inhibits key cascades implicated in MDR and HepG2 cell survival.CGFSVNLC is promising for overcoming drug resistance mechanisms and improving therapeutic outcomes against HepG2 cells.展开更多
Poly(vinyl alcohol)(PVA)hydrogels have garnered significant attention for tissue engineering,wound dressing,and electronic skin sensing applications.However,their poor mechanical performance severely restricts their m...Poly(vinyl alcohol)(PVA)hydrogels have garnered significant attention for tissue engineering,wound dressing,and electronic skin sensing applications.However,their poor mechanical performance severely restricts their multifunctional application in many scenarios.To address this limitation,PVA/tannic acid(TA)@carbon nanotubes(PVA/TA@CNTs)composite hydrogels with triple crosslinking networks were prepared through freezing-thawing and the solvent-induced shrinkage method,utilizing tannic acid-carbon nanotubes(TA@CNTs)as reinforcing units and a Ca^(2+)crosslinking strategy.The enhanced interfacial networks consisting of PVA crystalline domains,hydrogen bonding,and metal coordination endowed the composite hydrogel with a high mechanical strength,excellent flexibility,and fracture toughness,accompanied by a significant increase in crystallinity.The tensile strength and fracture toughness of the composite hydrogel reached up to about 7.0 MPa and 17.0MJ/m^(3),which were roughly 8 and 10 times higher than those of neat PVA hydrogel,respectively.The composite hydrogel demonstrated good cytocompatibility,significantly addressing the challenge of balancing structural reinforcement with biosafety in hydrogels.This methodology establishes a rational design for fabricating mechanically robust yet tough PVA hydrogels for biomedical applications.展开更多
BACKGROUND Syngeneic orthotopic tumor models offer an optimal functional tumor–immune interface for hepatocellular carcinoma research.Yet,unpredictable growth kinetics and spontaneous regression pose major obstacles....BACKGROUND Syngeneic orthotopic tumor models offer an optimal functional tumor–immune interface for hepatocellular carcinoma research.Yet,unpredictable growth kinetics and spontaneous regression pose major obstacles.Efficient induction protocols and continuous monitoring are therefore essential.Routine exploratory surgeries are ethically untenable,making non-invasive imaging modalities attractive alternatives.High-resolution magnetic resonance imaging and microcomputed tomography deliver detailed insights but incur substantial equipment costs,radiation risks,time demands,and require specialized expertise—challenges that limit their routine use.In contrast,ultrasound(US)imaging emerges as a cost-effective,radiation-free,and rapid approach,facilitating practical and ethical longitudinal assessment of tumor progression in preclinical studies.AIM To optimize the orthotopic hepatocellular carcinoma model and evaluate the potential of US imaging for accurate and cost-effective tumor monitoring.METHODS Hepatocellular carcinoma was induced in 28 Sprague Dawley rats by implanting 5×10^(6) N1S1 cells into the left lateral hepatic lobe.Tumor progression was monitored weekly via US.Upon reaching 100-150 mm^(3),an experimental group(n=14)received Sorafenib(40 mg/kg)orally on alternate days for 28 days;efficacy was compared to untreated controls.US accuracy was validated against micro-computed tomography,gross caliper measurements and histopathological analysis.Reliability and operator proficiency in US assessment were also evaluated.RESULTS US images procured 7-day post-surgery revealed a well-defined hypoechoic nodule at the left liver lobe tip,confirming successful tumor induction(mean volume 130±39 mm^(3)).Only three animals exhibited spontaneous regression by week 2,underscoring the model’s stability.Sorafenib treatment elicited a marked tumor reduction(678±103 mm^(3))vs untreated control(6005±1760 mm^(3)).US assessment demonstrated robust intra and interobserver reproducibility with high sensitivity and specificity for tumor detection.Moreover,US derived volumes correlated strongly with gross caliper measurements,histopathological analysis,and microcomputed tomography imaging,validating its reliability as a non-invasive monitoring tool in preclinical hepatocellular carcinoma studies.CONCLUSION The results demonstrate that US imaging is a reliable,cost-effective,and animal sparing approach with an easy tomaster protocol,enabling monitoring of tumor progression and therapeutic response in orthotopic liver tumor models.展开更多
Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is ge...Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.展开更多
The aim of this study was to develop a novel pharmaceutical excipient:an anion exchange resin.Initially,polystyrenedivinylbenzene(PS-DVB)microspheres were synthesized via suspension polymerization.Subsequently,these m...The aim of this study was to develop a novel pharmaceutical excipient:an anion exchange resin.Initially,polystyrenedivinylbenzene(PS-DVB)microspheres were synthesized via suspension polymerization.Subsequently,these microspheres served as a substrate for chloromethylation using methanol,formaldehyde,and chlorosulfonic acid.By optimizing the reaction conditions,the chloromethylated microspheres were characterized using infrared spectroscopy,scanning electron microscopy,and the Mohr method.Under optimal reaction conditions,the resulting products exhibited uniformity and spherical morphology,with an average particle size of approximately 190μm.The PS-DVB microspheres effectively incorporated chloromethyl groups,as evidenced by a chlorine content of 14.67%.Scanning electron microscopy analysis indicated that the appearance of the microspheres remained largely unchanged post-reaction.Overall,the research findings demonstrated the successful preparation of the anion exchange resin.Characterization and quality assessment confirmed that the ion exchange resin met the required standards.展开更多
Background:Diabetes mellitus(DM)is a prevalent chronic metabolic condition characterized by high blood sugar levels,resulting from insufficient insulin production or ineffective insulin use,posing substantial global h...Background:Diabetes mellitus(DM)is a prevalent chronic metabolic condition characterized by high blood sugar levels,resulting from insufficient insulin production or ineffective insulin use,posing substantial global health issues.Research on the relationship between glycemic status and the ratio of neutrophils to lymphocytes(NLR)and monocytes to lymphocytes(MLR)is limited.This study aimed to fill these knowledge gaps by examining the connection between DM and inflammatory markers within the Asir region.Methods:Data from 3545 participants were retrospectively analyzed.The dataset,gathered between 2021 and 2023,comprises 38 laboratory tests obtained from the Future Lab Pioneer database.The study's inclusion criteria focused on diabetes profile tests(glycated hemoglobin[HbA1c]and fasting blood glucose[FBG])and manually computed inflammatory markers(NLR and MLR),which were stratified by age and sex.Results:This study demonstrated significant differences in NLR levels compared with FBG levels across all adult age groups and adult female participants(p<0.0001),as well as among all elderly age groups(p=0.0006)and elderly women(p=0.01).MLR levels were significant in all adult age groups(p=0.04)and in adult women(p=0.02).When NLR and MLR were compared to HbA1c levels,a significant difference in the mean NLR was found in adult women(p=0.005).Additionally,the mean MLR levels were significant in all adult age groups(p=0.04)and adult women(p=0.02).Conclusion:Although a larger sample size is necessary for this research,the results indicate that NLR and MLR could serve as valuable indicators for evaluating inflammation in people with disrupted glucose metabolism,particularly in adult and female populations.展开更多
Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potentia...Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.展开更多
Cholelithiasis affects approximately 10%-20%of the adult population globally.And cholesterol accumulation and nucleation of cholesterol crystals are commonly recognized as the primary process in the initiation and pro...Cholelithiasis affects approximately 10%-20%of the adult population globally.And cholesterol accumulation and nucleation of cholesterol crystals are commonly recognized as the primary process in the initiation and progression of gallstones.Hydroxypropyl-β-cyclodextrin(HPCD)is a supramolecular host compound that can solubilize cholesterol,potentially serving as a preventative or therapeutic agent for cholelithiasis.However,we found that the administration of HPCD treatment did not impede the formation of gallstones in mice,mainly attributed to the pre-complexation of its cavity during the transition process.Here we synthesized a prodrug of HPCD and prepared a HPCD nanoparticle(HPCD-NP),which can be transported efficiently to the gallbladder through the hepatobiliary system following an intravenous injection.In the bile,the HPCD-NP degraded into free HPCD,bound to cholesterol crystals and gallstones within the gallbladder and effectively increased cholesterol solubilization,leading to gallstones regression.Given the established safety of both HPCD and cyclodextrin-based nanoparticles in numerous animal and human studies,HPCD-NP shows considerable promise for the prevention and treatment of human cholelithiasis.展开更多
Oseltamivir phosphate(OP),renowned as one of the most effective drugs for influenza treatment,encounters several challenges,including poor stability,difficulty in swallowing,and a bitter taste,thereby limiting its com...Oseltamivir phosphate(OP),renowned as one of the most effective drugs for influenza treatment,encounters several challenges,including poor stability,difficulty in swallowing,and a bitter taste,thereby limiting its compliance,particularly among children.Consequently,this study aimed to devise a novel sustained-release suspension of OP employing an ion exchange resin as a carrier to address these challenges.The OP-drug resin complex(OP-DRC)was synthesized utilizing ion exchange technology,while OP-coated microcapsules(OP-CM)were fabricated via the emulsion-evaporation method.The optimization of the formulation process for the OP sustained-release suspension was achieved through a combination of single-factor experimentation and orthogonal experimental design.Furthermore,the drug release kinetics and pharmacokinetic properties of the sustained-release suspension were thoroughly evaluated both in vitro and in vivo.Scanning electron microscopy(SEM),X-ray diffraction(XRD),and attenuated total reflectance Fourier-transform infrared spectroscopy(ATR-FTIR)analyses confirmed the formation of drug-resin complexes via ionic bonding.The in vitro cumulative release rates were found to be 16%(1 h),53%(6 h),and 84%(24 h),respectively.Notably,the self-made sustained-release suspension exhibited an extended half-life(21.518 h),delayed time to peak concentration(T_(max))(6 h),and reduced maximum plasma concentration(C_(max))(0.397μg/mL)in comparison to commercial granules(half-life=8.466 h;T_(max)=2 h;C_(max)=0.631μg/mL).Additionally,the area under the curve(AUC)indicated that the bioavailability of the self-made OP suspension surpassed that of the commercial OP granules by 101%.These findings underscored the successful development of an oral OP sustained-release suspension characterized by stability,tastelessness,ease of swallowing,convenient administration,and sustained-release properties,thereby potentially enhancing drug compliance among children.展开更多
Ulcerative colitis(UC)is an inflammatory condition of the intestine,resulting from an increase in oxidative stress and pro-inflammatory mediators.In this study,the extract of endophytic bacterium Rhizobium aegyptiacum...Ulcerative colitis(UC)is an inflammatory condition of the intestine,resulting from an increase in oxidative stress and pro-inflammatory mediators.In this study,the extract of endophytic bacterium Rhizobium aegyptiacum was prepared for the first time using liquid chromatography-mass spectrometry(LC-MS).In addition,also for the first time,the protective potential of R.aegyptiacum was revealed using an in vivo rat model of UC.The animals were grouped into four categories:normal control(groupⅠ),R.aegyptiacum(groupⅡ),acetic acid(AA)-induced UC(groupⅢ),and R.aegyptiacum-treated AA-induced UC(groupⅣ).In groupⅣ,R.aegyptiacum was administered at 0.2 mg/kg daily for one week before and two weeks after the induction of UC.After sacrificing the rats on the last day of the experiment,colon tissues were collected and subjected to histological,immunohistochemical,and biochemical investigations.There was a remarkable improvement in the histological findings of the colon tissues in groupⅣ,as revealed by hematoxylin and eosin(H&E)staining,Masson's trichrome staining,and periodic acid-Schiff(PAS)staining.Normal mucosal surfaces covered with a straight,intact,and thin brush border were revealed.Goblet cells appeared magenta in color,and there was a significant decrease in the distribution of collagen fibers in the mucosa and submucosal connective tissues.All these findings were comparable to the respective characteristics of the control group.Regarding cyclooxygenase-2(COX-2)immunostaining,a weak immune reaction was shown in most cells.Moreover,the colon tissues were examined using a scanning electron microscope,which confirmed the results of histological assessment.A regular polygonal unit pattern was seen with crypt orifices of different sizes and numerous goblet cells.Furthermore,the levels of catalase(CAT),myeloperoxidase(MPO),nitric oxide(NO),interleukin-6(IL-6),and interlukin-1β(IL-1β)were determined in the colonic tissues of the different groups using colorimetric assay and enzyme-linked immunosorbent assay(ELISA).In comparison with groupⅢ,groupⅣexhibited a significant rise(P<0.05)in the CAT level but a substantial decline(P<0.05)in the NO,MPO,and inflammatory cytokine(IL-6 and IL-1β)levels.Based on reverse transcription-quantitative polymerase chain reaction(RT-qPCR),the tumor necrosis factor-α(TNF-α)gene expression was upregulated in groupⅢ,which was significantly downregulated(P<0.05)by treatment with R.aegyptiacum in groupⅣ.On the contrary,the heme oxygenase-1(HO-1)gene was substantially upregulated in groupⅣ.Our findings imply that the oral consumption of R.aegyptiacum ameliorates AA-induced UC in rats by restoring and reestablishing the mucosal integrity,in addition to its anti-oxidant and anti-inflammatory effects.Accordingly,R.aegyptiacum is potentially effective and beneficial in human UC therapy,which needs to be further investigated in future work.展开更多
Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to t...Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to the challenges posed by the inaccessibility of deep-seated tumors.Herein,we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel.The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug,and subsequently embedded into a hydrogel matrix.The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions,forming a drug depot for sustained release and long-lasting treatment.As the hydrogel gradually degrades,the nanoassemblies are internalized by tumor cells.The redox response ability enables them to be selectively activatedwithin tumor cells to trigger the release of docetaxel and oxaliplatin,exerting a synergistic anti-tumor effect.We find that the combination effectively induces immunogenic cell death of gastric tumor,enhancing antitumor immune responses.This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.展开更多
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
文摘Nanotechnology has revolutionized drug delivery,particularly through nanoformulations of phytoconstituents,enhancing their therapeutic potential.Despite their broad bioactivities,plant-based compounds often suffer from poor bioavailability and stability.Nanoformulations address these limitations by improving solubility,targeted delivery,and controlled release.This approach opens new possibilities for treating chronic diseases like cancer,diabetes,and neurodegenerative disorders.This review aims to examine recent advancements in nanotechnology-based formulation strategies designed to enhance the delivery,stability,and therapeutic efficacy of phytochemicals and also discusses regulatory issues,safety concerns,scalability,and cost-effectiveness.Emphasis was placed on nanoformulation techniques employed for key phytoconstituents such as curcumin,resveratrol,epigallocatechin gallate,and quercetin.The most commonly employed nanocarriers included polymeric nanoparticles,solid lipid nanoparticles,and liposomes.These formulations significantly improved the solubility,stability,and controlled release profiles of phytochemicals.In vitro and in vivo studies demonstrated enhanced anti-inflammatory,anticancer,and antioxidant activities.Moreover,surface-modified and targeted nanoparticles showed promise in increasing site-specific targeting and enhancing bioavailability of the encapsulated compounds.Nanoformulations present a promising strategy for overcoming the pharmacokinetic limitations of phytochemicals.Despite encouraging preclinical results,further studies are needed to address issues related to long-term safety,clinical efficacy,and regulatory approval for successful clinical translation.
基金from"XingLiao Talent Program"of Liaoning Province(No.XLYC2203156)Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program(No.RC220397)are greatly acknowledged。
文摘Mesoporous silica nanoparticles(MsNs)are thought to be an attractive drug delivery material because of their advantages including high specific surface area,tunable pore size and morphology,easy sur-face modification and good biocompatibility.However,as a result of the poor biodegradability of MsNs,their biomedical applications are limited.To break the bottleneck of limited biomedical applications of MSNs,more and more researchers tend to design biodegradable MSNs(b-MSNs)nanosystems to obtain biodegradable as well as safe and reliable drug delivery carriers.In this review,we focused on sum-marizing strategies to improve the degradability of MsNs and innovatively proposed a series of advan-tages of b-MsNs,including controlled cargo release behavior,multifunctional frameworks,nano-catalysis,bio-imaging capabilities and enhanced therapeutic effects.Based on these advantages,we have inno-vatively summarized the applications of b-MsNs for enhanced tumor theranostics,including enhanced chemotherapy,delivery of nanosensitizers,gas molecules and biomacromolecules,initiation of immune response,synergistic therapies and image-guided tumor diagnostics.Finally,the challenges and further clinical translation potential of nanosystems based on b-MsNs are fully discussed and prospected.We believe that such b-MsNs delivery carriers will provide a timely reference for further applications in tu-mor theranostics.
基金support of Isfahan University of Medical Sciences(Project code No.#1401262).
文摘Mimicking the hierarchical structure of the skin is one of the most important strategies in skin tissue engineering.Monolayer wound dressings are usually not able to provide several functions at the same time and cannot meet all clinical needs.In order to maximize therapeutic efficiency,herein,we fabricated a Tri-layer wound dressing,where the middle layer was fabricated via 3D-printing and composed of alginate,tragacanth and zinc oxide nanoparticles(ZnO NPs).Both upper and bottom layers were constructed using electrospinning technique;the upper layer was made of hydrophobic polycaprolactone to mimic epidermis,while the bottom layer consisted of Soluplus■ and insulin-like growth factor-1(IGF-1)to promote cell behavior.Swelling,water vapor permeability and tensile properties of the dressings were evaluated and the Tri-layer dressing exhibited impressive antibacterial activity and cell stimulation following by the release of ZnO NPs and IGF-1.Additionally,the Tri-layer dressing led to faster healing of full-thicknesswound in ratmodel compared to monolayer and Bilayer dressings.Overall,the evidence confirmed that the Trilayer wound dressing is extremely effective for full-thickness wound healing.
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS),China(No.2021-I2M-1-026)。
文摘Intratumoral bacteria have been proven to be widely exist in tumors,different tumors of different systems have different types of characteristic bacteria.Intratumoral bacteria will become a new and important biomarker in the full cycle of tumor development.This article emphasizes the key role of intratumoral bacteria in the occurrence and progress of tumors,including promoting tumor development,accelerating tumor metastasis and promoting tumor cell resistance.In addition,this article also summarizes the application of intratumoral bacteria in tumor diagnosis and prognosis.Especially,this article outlines the treatment strategies of intratumoral bacteria,including non-nanodelivery therapy strategies and nanodelivery therapy strategies,such as antibiotic,macromolecular,inflammatory factor inhibitors,near-infrared-photothermal therapy,inorganic antibacterial agents,reactive species and microbes therapy,in these strategies,nano delivery system provides a promising treatment that solves the problem of drug resistance,reducing toxicity and improving patient compliance.This article is hoped to guide future research on intratumoral bacteria on tumors.
文摘Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.
文摘Background:Luliconazole is an imidazole antifungal drug mainly used to treat dermatophytic infections including tinea pedis,tinea cruris,and tinea corporis.Objective:The purpose of this research was to synthesize a transferosomal gel incorporating luliconazole for external applications.Materials and methods:The preparation method employed thin film hydration to prepare transferosomes loaded with luliconazole with lecithin and tween 80 at different concentrations.The transferosomes formed were characterized in terms of particle size and entrapment efficiency.Finally,the prepared transferosomes were applied in a carbopol gel base and characterized for drug content,pH,spreadability,viscosity,in vitro release profile,and antifungal studies.Results:The synthesized luliconazole transferosomes had high entrapment efficiency of 74.45%,and 92.75%,with particle size ranging between 60 and 200 nm.The shape of the transferosomes was established using scanning electron microscopy;the results depicted spherical-shaped vesicles.The in vitro release study also suggested that the entrapment efficiency influences in vitro release where there is a negative relationship between the two.The gel formulation revealed a good antifungal effect.Conclusion:The luliconazole transferosomal gel exhibited a sustained release profile of the drug and thus may lessen the number of applications required,thereby enhancing patient compliance.
文摘Objective:Prostate cancer(PCA)is the second most widespread cancer among men globally,with a rising mortality rate.Enzyme-responsive lipid nanoparticles(ERLNs)are promising vectors for the selective delivery of anticancer agents to tumor cells.The goal of this study is to fabricate ERLNs for dual delivery of gefitinib(GF)and simvastatin(SV)to PCA cells.Methods:ERLNs loaded with GF and SV(ERLNGFSV)were assembled using bottomup and top-down techniques.Subsequently,these ERLN cargoes were coated with triacylglycerol,and phospholipids and capped with chitosan(CS).The ERLNGFSV,and CS engineered ERLNGFSV(CERLNGFSV)formulations were characterized for particle size(PS),zeta potential(ZP),and polydispersity index(PDI).The biocompatibility,and cytotoxicity of the plain and GF plus SV-loaded ERLN cargoes were assessed using erythrocytes and PC-3 cell line.Additionally,molecular docking simulations(MDS)were conducted to examine the influence of GF and SV on succinate dehydrogenase(SDH),glutathione peroxidase-4(GPX-4),and 5α-reductase(5α-RD).Results:These results showed that plain,ERLNGFSV,and CERLNGFSV cargoes have a nanoscale size and homogeneous appearance.Moreover,ERLNGFSV and CERLNGFSV were biocompatible,with no detrimental effects on erythrocytes.Treatment with GF,SV,GF plus SV,ERLNGFSV,and CERLNGFSV significantly reduced the viability of PC-3 cells compared to control cells.Particularly,the blend of GF and SV,as well as ERLNGFSV and CERLNGFSV augmented PC-3 cell death.Also,treating PC-3 cells with free drugs,their combination,ERLNGFSV,and CERLNGFSV formulations elevated the percentage of apoptotic cells.MDS studies demonstrated that GF and SV interact with the active sites of SDH,GPX-4,and 5α-reductase.Conclusions:This study concludes that SVGF combination and ERLNs loading induce particular delivery,and synergism on PC-3 death through action on multiple pathways involved in cell proliferation,and apoptosis,besides the interaction with SDH,GPX-4,and 5α-RD.Therefore,GFSV-loaded ERLN cargoes are a promising strategy for PCA treatment.In vivo studies are necessary to confirm these findings for clinical applications.
基金financially supported by the National Natural Science Foundation of China(No.82161138029)the Basic Research Projects of Liaoning Provincial Department of Education(No.LJKZZ20220109)the Shenyang Youth Science and Technology Innovation Talents Program(No.RC210452).
文摘Photodynamic therapy(PDT)not only directly eradicates tumor cells but also boosts immunogenicity,promoting antigen presentation and immune cell infiltration.However,the robust antioxidant defense mechanisms within tumor cells significantly weaken the efficacy of photodynamic immunotherapy.Herein,a supramolecular hybrid nanoassembly is constructed by exploring the synergistic effects of the photodynamic photosensitizer(pyropheophorbide a,PPa)and the ferroptosis inducer(erastin).The erastinmediated inhibition of system X_(c)−significantly downregulates glutathione(GSH)expression,amplifying intracellular oxidative stress,leading to pronounced cell apoptosis,and promoting the release of damageassociated molecular patterns(DAMPs).Additionally,the precise cooperation of PPa and erastin enhances ferroptosis efficiency,exacerbating the accumulation of lipid peroxides(LPOs).Ultimately,LPOs serve as a“find me”signal,while DMAPs act as an“eat me”signal,collectively promoting dendritic cell maturation,enhancing infiltration of the cytotoxic T lymphocytes,and eliciting a robust immune response.This study opens new horizons for enhancing tumor immunotherapy through simultaneous ferroptosis-PDT.
基金Support Project(RSPD2024R1037),King Saud University,Riyadh,Saudi Arabia.
文摘Background:Hepatocellular carcinoma(HCC)is a health problem due to multi-drug resistance(MDR).Codelivery of multiple oncotherapy in one cargo as chimeric cancer therapy(CCT)is suggested as a solution for MDR.This study aims to engineer chitosan-coated nanostructure lipid carriers(NLCs)loaded with gefitinib(GF)and simvastatin(SV)as CCT for HCC.Methods:Both GF and SV-loaded nanostructure lipids carriers(GFSVNLC)and chitosan-capped GF and SV-loaded nanostructure lipids carriers(CGFSVNLC)formulations were assembled by topdown techniques.Moreover,particle size(PS),zeta potential(ZP),and polydispersity index(PDI)were measured by Zetasizer.The biosafety of GFSVNLC preparations was investigated by using erythrocytes as a biological model.The cytotoxic,and apoptotic effects of the prepared GFSVNLCs were investigated using HepG2 cell lines as a substitute model for HCC.The effect of GF,SV,and NLC composition on JNK3,HDAC6,and telomerase was studied using molecular docking simulation(MDS).Results:The present results revealed that the obtained GFSVNLC and CGFSVNLC have nanosized and consistent,CS coating shifts anionic ZP of GFSVNLC into CGFSVNLC with cationic ZP.Moreover,both formulations are biocompatible as indicated by their gentle effect on erythrocyte hemolysis.The treatment of HepG2 cells with GFSVNLC,and CGFSVNLC induced marked cell death compared to other groups with a decrease of IC50.Equally,the percentage of the apoptotic HepG2 cells was increased upon treatment of the cells with GFSV,GFSVNLC,and CGFSVNLC compared to the control group.Additionally,GF,SV,stearic acid(SA),and oleic acid(OA)modulate the activity of JNK3,HDAC6,and telomerase.Conclusions:This study suggests CGFSVNLC achieves codelivery,selective targeting,and enhancing the synergistic effect of GF and SV for inducing HepG2 cell death.Mechanistically,CGFSVNLC inhibits key cascades implicated in MDR and HepG2 cell survival.CGFSVNLC is promising for overcoming drug resistance mechanisms and improving therapeutic outcomes against HepG2 cells.
基金financially supported by the China Postdoctoral Science Foundation(No.2024M751205)the Natural Science Foundation of Jiangsu Province(JSNSF)(No.BK20230694)。
文摘Poly(vinyl alcohol)(PVA)hydrogels have garnered significant attention for tissue engineering,wound dressing,and electronic skin sensing applications.However,their poor mechanical performance severely restricts their multifunctional application in many scenarios.To address this limitation,PVA/tannic acid(TA)@carbon nanotubes(PVA/TA@CNTs)composite hydrogels with triple crosslinking networks were prepared through freezing-thawing and the solvent-induced shrinkage method,utilizing tannic acid-carbon nanotubes(TA@CNTs)as reinforcing units and a Ca^(2+)crosslinking strategy.The enhanced interfacial networks consisting of PVA crystalline domains,hydrogen bonding,and metal coordination endowed the composite hydrogel with a high mechanical strength,excellent flexibility,and fracture toughness,accompanied by a significant increase in crystallinity.The tensile strength and fracture toughness of the composite hydrogel reached up to about 7.0 MPa and 17.0MJ/m^(3),which were roughly 8 and 10 times higher than those of neat PVA hydrogel,respectively.The composite hydrogel demonstrated good cytocompatibility,significantly addressing the challenge of balancing structural reinforcement with biosafety in hydrogels.This methodology establishes a rational design for fabricating mechanically robust yet tough PVA hydrogels for biomedical applications.
基金Supported by Amrita Vishwa Vidyapeetham Seed Grant,No.K-PHAR-24-722DST INSPIRE Fellowship,No.IF190226.
文摘BACKGROUND Syngeneic orthotopic tumor models offer an optimal functional tumor–immune interface for hepatocellular carcinoma research.Yet,unpredictable growth kinetics and spontaneous regression pose major obstacles.Efficient induction protocols and continuous monitoring are therefore essential.Routine exploratory surgeries are ethically untenable,making non-invasive imaging modalities attractive alternatives.High-resolution magnetic resonance imaging and microcomputed tomography deliver detailed insights but incur substantial equipment costs,radiation risks,time demands,and require specialized expertise—challenges that limit their routine use.In contrast,ultrasound(US)imaging emerges as a cost-effective,radiation-free,and rapid approach,facilitating practical and ethical longitudinal assessment of tumor progression in preclinical studies.AIM To optimize the orthotopic hepatocellular carcinoma model and evaluate the potential of US imaging for accurate and cost-effective tumor monitoring.METHODS Hepatocellular carcinoma was induced in 28 Sprague Dawley rats by implanting 5×10^(6) N1S1 cells into the left lateral hepatic lobe.Tumor progression was monitored weekly via US.Upon reaching 100-150 mm^(3),an experimental group(n=14)received Sorafenib(40 mg/kg)orally on alternate days for 28 days;efficacy was compared to untreated controls.US accuracy was validated against micro-computed tomography,gross caliper measurements and histopathological analysis.Reliability and operator proficiency in US assessment were also evaluated.RESULTS US images procured 7-day post-surgery revealed a well-defined hypoechoic nodule at the left liver lobe tip,confirming successful tumor induction(mean volume 130±39 mm^(3)).Only three animals exhibited spontaneous regression by week 2,underscoring the model’s stability.Sorafenib treatment elicited a marked tumor reduction(678±103 mm^(3))vs untreated control(6005±1760 mm^(3)).US assessment demonstrated robust intra and interobserver reproducibility with high sensitivity and specificity for tumor detection.Moreover,US derived volumes correlated strongly with gross caliper measurements,histopathological analysis,and microcomputed tomography imaging,validating its reliability as a non-invasive monitoring tool in preclinical hepatocellular carcinoma studies.CONCLUSION The results demonstrate that US imaging is a reliable,cost-effective,and animal sparing approach with an easy tomaster protocol,enabling monitoring of tumor progression and therapeutic response in orthotopic liver tumor models.
基金funded by the National Natural Science Foundation of China(22478438,32401048,and 82273882)the Science Fund for Distinguished Young Scholars of Jiangsu Province(BK20240098)the Special Research Fund from the State Key Laboratory of Natural Medicines at China Pharmaceutical University(SKLNMZZ2024JS19).
文摘Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.
基金2023 Nantong Jianghai Talents Project,the Nantong Social Livelihood Science and Technology Plan for 2023the 2022 New Drugs and Platform Enhancement Project of the Yangtze Delta Drug Advanced Research Institute.Additionally,support was provided by the Zhenjiang Science and Technology Project(Grant No.SH2020048)+2 种基金the China Postdoctoral Science Foundation(Grant No.2020M681532)the Jiangsu Planned Projects for Postdoctoral Research Funds(Grant No.2020Z209)the Natural Science Research Projects of Universities in Jiangsu Province(Grant No.20KJD350001).
文摘The aim of this study was to develop a novel pharmaceutical excipient:an anion exchange resin.Initially,polystyrenedivinylbenzene(PS-DVB)microspheres were synthesized via suspension polymerization.Subsequently,these microspheres served as a substrate for chloromethylation using methanol,formaldehyde,and chlorosulfonic acid.By optimizing the reaction conditions,the chloromethylated microspheres were characterized using infrared spectroscopy,scanning electron microscopy,and the Mohr method.Under optimal reaction conditions,the resulting products exhibited uniformity and spherical morphology,with an average particle size of approximately 190μm.The PS-DVB microspheres effectively incorporated chloromethyl groups,as evidenced by a chlorine content of 14.67%.Scanning electron microscopy analysis indicated that the appearance of the microspheres remained largely unchanged post-reaction.Overall,the research findings demonstrated the successful preparation of the anion exchange resin.Characterization and quality assessment confirmed that the ion exchange resin met the required standards.
文摘Background:Diabetes mellitus(DM)is a prevalent chronic metabolic condition characterized by high blood sugar levels,resulting from insufficient insulin production or ineffective insulin use,posing substantial global health issues.Research on the relationship between glycemic status and the ratio of neutrophils to lymphocytes(NLR)and monocytes to lymphocytes(MLR)is limited.This study aimed to fill these knowledge gaps by examining the connection between DM and inflammatory markers within the Asir region.Methods:Data from 3545 participants were retrospectively analyzed.The dataset,gathered between 2021 and 2023,comprises 38 laboratory tests obtained from the Future Lab Pioneer database.The study's inclusion criteria focused on diabetes profile tests(glycated hemoglobin[HbA1c]and fasting blood glucose[FBG])and manually computed inflammatory markers(NLR and MLR),which were stratified by age and sex.Results:This study demonstrated significant differences in NLR levels compared with FBG levels across all adult age groups and adult female participants(p<0.0001),as well as among all elderly age groups(p=0.0006)and elderly women(p=0.01).MLR levels were significant in all adult age groups(p=0.04)and in adult women(p=0.02).When NLR and MLR were compared to HbA1c levels,a significant difference in the mean NLR was found in adult women(p=0.005).Additionally,the mean MLR levels were significant in all adult age groups(p=0.04)and adult women(p=0.02).Conclusion:Although a larger sample size is necessary for this research,the results indicate that NLR and MLR could serve as valuable indicators for evaluating inflammation in people with disrupted glucose metabolism,particularly in adult and female populations.
基金supported by National Natural Science Foundation of China(82374296,82271965,62331021)Development Project of Shanghai Peak Disciplines-Integrated Medicine(201801)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Shanghai Municipal Science and Technology Explorer Project(23TS1400500).
文摘Ischemic stroke is currently the second leading cause of death worldwide,and insufficient endogenous neurogenesis is the greatest cause of post-stroke disability.MicroRNAs have been proven to hold therapeutic potential,unfortunately,they have a low stability that hinders their clinical usage.Our earlier work revealed that Panax notoginseng derived exosome like nanoparticles,namely PDNs have potential to bypass BBB and reduce the cerebral ischemia/reperfusion(CI/R)damage.In this study,we employed microRNA-124 as a model therapeutic gene,utilizing its engineered variant Agomir-124(Ago124)to optimize loading efficiency.The therapeutic effects of Ago124@R-PDN were further assessed in several sets of experiments.Pharmacokinetic study showed that erythrocyte membrane extended the half-life of PDNs from 7 min to 11.3 h,and the loading efficiency of Ago124 reached 40%.In an in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model,Ago124@R-PDN enhanced IL-10 production in microglia by 67%(vs 11.7%with free Ago124),and promoted Tuj1+neuronal differentiation by 2.23-fold compared with vehicle.Also,Ago124@R-PDN brought gene cargo into the brain,alleviated infarct volume,and improved functional behaviors in model mice.At last,we demonstrated that surface glycosyl of PDN facilitated its brain-entering ability by being recognized by sodium-glucose linked transporter-1 protein.In conclusion,our erythrocyte fused PDNs offer a promising strategy for delivering biomacromolecule to treat brain diseases.
基金financially supported by the National Natural Science Foundation of China(Nos.82102195,22071275 and 22271323)Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQ-MSX1073)Scientific and Technological Research Program of Chongqing Municipal Education Commission(No.KJQN202100454)。
文摘Cholelithiasis affects approximately 10%-20%of the adult population globally.And cholesterol accumulation and nucleation of cholesterol crystals are commonly recognized as the primary process in the initiation and progression of gallstones.Hydroxypropyl-β-cyclodextrin(HPCD)is a supramolecular host compound that can solubilize cholesterol,potentially serving as a preventative or therapeutic agent for cholelithiasis.However,we found that the administration of HPCD treatment did not impede the formation of gallstones in mice,mainly attributed to the pre-complexation of its cavity during the transition process.Here we synthesized a prodrug of HPCD and prepared a HPCD nanoparticle(HPCD-NP),which can be transported efficiently to the gallbladder through the hepatobiliary system following an intravenous injection.In the bile,the HPCD-NP degraded into free HPCD,bound to cholesterol crystals and gallstones within the gallbladder and effectively increased cholesterol solubilization,leading to gallstones regression.Given the established safety of both HPCD and cyclodextrin-based nanoparticles in numerous animal and human studies,HPCD-NP shows considerable promise for the prevention and treatment of human cholelithiasis.
基金2023 Nantong Jianghai Talents Project2023 Nantong Social Livelihood Science and Technology Plan+4 种基金2021 Jurong Social Development Science&Technology Program(Grant No.ZA42109)2022 New Drugs and Platform Enhancement Project of the Yangtze Delta Drug Advanced Research InstituteChina Postdoctoral Science Foundation(Grant No.2020M681532)Jiangsu Planned Projects for Postdoctoral Research Funds(Grant No.2020Z209)Natural Science Research Projects of Universities in Jiangsu Province(Grant No.20KJD350001)。
文摘Oseltamivir phosphate(OP),renowned as one of the most effective drugs for influenza treatment,encounters several challenges,including poor stability,difficulty in swallowing,and a bitter taste,thereby limiting its compliance,particularly among children.Consequently,this study aimed to devise a novel sustained-release suspension of OP employing an ion exchange resin as a carrier to address these challenges.The OP-drug resin complex(OP-DRC)was synthesized utilizing ion exchange technology,while OP-coated microcapsules(OP-CM)were fabricated via the emulsion-evaporation method.The optimization of the formulation process for the OP sustained-release suspension was achieved through a combination of single-factor experimentation and orthogonal experimental design.Furthermore,the drug release kinetics and pharmacokinetic properties of the sustained-release suspension were thoroughly evaluated both in vitro and in vivo.Scanning electron microscopy(SEM),X-ray diffraction(XRD),and attenuated total reflectance Fourier-transform infrared spectroscopy(ATR-FTIR)analyses confirmed the formation of drug-resin complexes via ionic bonding.The in vitro cumulative release rates were found to be 16%(1 h),53%(6 h),and 84%(24 h),respectively.Notably,the self-made sustained-release suspension exhibited an extended half-life(21.518 h),delayed time to peak concentration(T_(max))(6 h),and reduced maximum plasma concentration(C_(max))(0.397μg/mL)in comparison to commercial granules(half-life=8.466 h;T_(max)=2 h;C_(max)=0.631μg/mL).Additionally,the area under the curve(AUC)indicated that the bioavailability of the self-made OP suspension surpassed that of the commercial OP granules by 101%.These findings underscored the successful development of an oral OP sustained-release suspension characterized by stability,tastelessness,ease of swallowing,convenient administration,and sustained-release properties,thereby potentially enhancing drug compliance among children.
基金funding provided by The Science,Technology&Innovation Funding Authority(STDF)in cooperation with The Egyptian Knowledge Bank(EKB).
文摘Ulcerative colitis(UC)is an inflammatory condition of the intestine,resulting from an increase in oxidative stress and pro-inflammatory mediators.In this study,the extract of endophytic bacterium Rhizobium aegyptiacum was prepared for the first time using liquid chromatography-mass spectrometry(LC-MS).In addition,also for the first time,the protective potential of R.aegyptiacum was revealed using an in vivo rat model of UC.The animals were grouped into four categories:normal control(groupⅠ),R.aegyptiacum(groupⅡ),acetic acid(AA)-induced UC(groupⅢ),and R.aegyptiacum-treated AA-induced UC(groupⅣ).In groupⅣ,R.aegyptiacum was administered at 0.2 mg/kg daily for one week before and two weeks after the induction of UC.After sacrificing the rats on the last day of the experiment,colon tissues were collected and subjected to histological,immunohistochemical,and biochemical investigations.There was a remarkable improvement in the histological findings of the colon tissues in groupⅣ,as revealed by hematoxylin and eosin(H&E)staining,Masson's trichrome staining,and periodic acid-Schiff(PAS)staining.Normal mucosal surfaces covered with a straight,intact,and thin brush border were revealed.Goblet cells appeared magenta in color,and there was a significant decrease in the distribution of collagen fibers in the mucosa and submucosal connective tissues.All these findings were comparable to the respective characteristics of the control group.Regarding cyclooxygenase-2(COX-2)immunostaining,a weak immune reaction was shown in most cells.Moreover,the colon tissues were examined using a scanning electron microscope,which confirmed the results of histological assessment.A regular polygonal unit pattern was seen with crypt orifices of different sizes and numerous goblet cells.Furthermore,the levels of catalase(CAT),myeloperoxidase(MPO),nitric oxide(NO),interleukin-6(IL-6),and interlukin-1β(IL-1β)were determined in the colonic tissues of the different groups using colorimetric assay and enzyme-linked immunosorbent assay(ELISA).In comparison with groupⅢ,groupⅣexhibited a significant rise(P<0.05)in the CAT level but a substantial decline(P<0.05)in the NO,MPO,and inflammatory cytokine(IL-6 and IL-1β)levels.Based on reverse transcription-quantitative polymerase chain reaction(RT-qPCR),the tumor necrosis factor-α(TNF-α)gene expression was upregulated in groupⅢ,which was significantly downregulated(P<0.05)by treatment with R.aegyptiacum in groupⅣ.On the contrary,the heme oxygenase-1(HO-1)gene was substantially upregulated in groupⅣ.Our findings imply that the oral consumption of R.aegyptiacum ameliorates AA-induced UC in rats by restoring and reestablishing the mucosal integrity,in addition to its anti-oxidant and anti-inflammatory effects.Accordingly,R.aegyptiacum is potentially effective and beneficial in human UC therapy,which needs to be further investigated in future work.
基金supported by National Natural Science Foundation of China(No.82161138029)Liaoning Revitalization Talents Program(No.XLYC2402040)the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007).
文摘Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to the challenges posed by the inaccessibility of deep-seated tumors.Herein,we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel.The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug,and subsequently embedded into a hydrogel matrix.The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions,forming a drug depot for sustained release and long-lasting treatment.As the hydrogel gradually degrades,the nanoassemblies are internalized by tumor cells.The redox response ability enables them to be selectively activatedwithin tumor cells to trigger the release of docetaxel and oxaliplatin,exerting a synergistic anti-tumor effect.We find that the combination effectively induces immunogenic cell death of gastric tumor,enhancing antitumor immune responses.This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.
