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Helicobacter pylori (H. pylori) is a recalcitrant pathogen, which can cause gastric disorders. During the past decades, polypharmacy-based regimens, such as triple and quadruple therapies have been widely used against H. pylori. However, polyantibiotic therapies can disturb the host gastric/gut microbiota and lead to antibiotic resistance. Thus, simpler but more effective approaches should be developed. Here, some recent advances in nanostructured drug delivery systems to treat H. pylori infection are summarized. Also, for the first time, a drug release paradigm is proposed to prevent H. pylori antibiotic resistance along with an IVIVC model in order to connect the drug release profile with a reduction in bacterial colony counts. Then, local delivery systems including mucoadhesive, mucopenetrating, and cytoadhesive nanobiomaterials are discussed in the battle against H. pylori infection. Afterward, engineered delivery platforms including polymer-coated nanoemulsions and polymer-coated nanoliposomes are poposed. These bioinspired platforms can contain an antimicrobial agent enclosed within smart multifunctional nanoformulations. These bioplatforms can prevent the development of antibiotic resistance, as well as specifically killing H. pylori with no or only slight negative effects on the host gastrointestinal microbiota. Finally, the essential checkpoints that should be passed to confirm the potential effectiveness of anti-H. pylori nanosystems are discussed.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Nanotecnología , Polímeros/farmacologíaRESUMEN
Targeted nanoparticle platforms designed to induce cell death by apoptosis can bypass the resistance mechanisms of cancer cells. With this in mind we have constructed a new cancer-targeting peptide-functionalized nanoparticle using gold nanoparticles (AuNPs) and a thioctic acid-DMPGTVLP peptide (TA-peptide) conjugate. Morphological analysis of the nanoparticles by transmission electron microscopy showed average diameters of about 3.52 nm and 26.2 nm for the AuNP core and shell, respectively. Strong affinity toward the nucleolin receptors of breast cancer cell lines MCF-7 and T47D was observed for the TA-peptide gold nanoparticles (TAP@AuNPs) based on IC50 values. Furthermore, the nanoparticles showed excellent hemocompatibility. Quantitative results of atomic absorption showed improved uptake of TAP@AuNPs. Treatment of the cells with TAP@AuNPS resulted in greater release of cytochrome c following caspase-3/7 activation compared with free TA-peptide. The cytosolic level of adenosine triphosphate for TAP@AuNPs was higher than in controls. Higher anti-tumor efficiency was observed for TAP@AuNPs than TA-peptide compared with phosphate-buffered saline after intratumoral injection in tumor-bearing mice. It can be concluded that the design and development of a receptor-specific peptide-AuNP platform will be valuable for theranostic applications in cancer nanomedicine.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Oro/química , Nanopartículas del Metal/química , Animales , Línea Celular Tumoral , Humanos , RatonesRESUMEN
A novel series of benzylpyridinium-based benzoheterocycles (benzimidazole, benzoxazole or benzothiazole) were designed as potent acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The title compounds 4a-q were conveniently synthesized via condensation reaction of 1,2-phenylenediamine, 2-aminophenol or 2-aminothiophenol with pyridin-4-carbalehyde, followed by N-benzylation using various benzyl halides. The results of in vitro biological assays revealed that most of them, especially 4c and 4g, had potent anticholinesterase activity comparable or more potent than reference drug, donepezil. The kinetic study demonstrated that the representative compound 4c inhibits AChE in competitive manner. According to the ligand-enzyme docking simulation, compound 4c occupied the active site at the vicinity of catalytic triad. The compounds 4c and 4g were found to be inhibitors of Aß self-aggregation as well as AChE-induced Aß aggregation. Meanwhile, these compounds could significantly protect PC12 cells against H2O2-induced injury and showed no toxicity against HepG2 cells. As multi-targeted structures, compounds 4c and 4g could be considered as promising candidate for further lead developments to treat Alzheimer's disease.
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Compuestos Heterocíclicos con 2 Anillos/farmacología , Fármacos Neuroprotectores/farmacología , Compuestos de Piridinio/farmacología , Acetilcolinesterasa/química , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Animales , Butirilcolinesterasa/metabolismo , Línea Celular Tumoral , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/toxicidad , Diseño de Fármacos , Electrophorus , Compuestos Heterocíclicos con 2 Anillos/síntesis química , Compuestos Heterocíclicos con 2 Anillos/metabolismo , Compuestos Heterocíclicos con 2 Anillos/toxicidad , Caballos , Humanos , Peróxido de Hidrógeno/farmacología , Cinética , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/toxicidad , Estrés Oxidativo/efectos de los fármacos , Fragmentos de Péptidos/efectos de los fármacos , Fragmentos de Péptidos/metabolismo , Unión Proteica , Multimerización de Proteína/efectos de los fármacos , Compuestos de Piridinio/síntesis química , Compuestos de Piridinio/metabolismo , Compuestos de Piridinio/toxicidad , Ratas , TorpedoRESUMEN
Two series of novel coumarin derivatives, substituted at 3 and 7 positions with aminoalkoxy groups, are synthesized, characterized, and screened. The effect of amine substituents and the length of cross-linker are investigated in acetyl- and butyrylcholinesterase (AChE and BuChE) inhibition. Target compounds show moderate to potent inhibitory activities against AChE and BuChE. 3-(3,4-Dichlorophenyl)-7-[4-(diethylamino)butoxy]-2H-chromen-2-one (4y) is identified as the most potent compound against AChE (IC50 =0.27â µm). Kinetic and molecular modeling studies affirmed that compound 4y works in a mixed-type way and interacts simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, compound 4y blocks ß-amyloid (Aß) self-aggregation with a ratio of 44.11 % at 100â µm and significantly protects PC12 cells from H2 O2 -damage in a dose-dependent manner.
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Cumarinas/química , Ligandos , Fármacos Neuroprotectores/química , Acetilcolinesterasa/química , Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/metabolismo , Animales , Apoptosis/efectos de los fármacos , Sitios de Unión , Butirilcolinesterasa/química , Butirilcolinesterasa/metabolismo , Dominio Catalítico , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Cumarinas/farmacología , Cumarinas/uso terapéutico , Humanos , Peróxido de Hidrógeno/toxicidad , Concentración 50 Inhibidora , Cinética , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Células PC12 , Ratas , Relación Estructura-ActividadRESUMEN
CONTEXT: Curcumin, a naturally occurring polyphenol, has been extensively studied for its broad-spectrum anticancer effects. The potential benefits are, however, limited due to its poor water solubility and rapid degradation which result in low bioavailability on administration. OBJECTIVES: This study encapsulates curcumin in nanoliposomes including an integrin-homing peptide combined with a C end R neuropilin-1 targeting motif for targeted delivery and receptor-mediated internalization, respectively. MATERIALS AND METHODS: The linear GHHNGR (Glycine-Histidine-Histidine-Asparagine-Glycine-Arginine) was synthesized through F-moc chemistry on 2-chlorotrityl chloride resin and conjugated to oleic acid. The lipoyl-peptide units were then co-assembled with lecithin and 0-75 mole % Tween-80 into liposomes. Curcumin was passively entrapped using a film hydration technique and its degradation profile was examined within seven consecutive days. The cytotoxic effects of the curcumin-loaded liposomes were studied on MCF-7 and MDA-MB-468, during 24 h exposure in MTT assay. RESULTS: The maximum curcumin entrapment (15.5% W/W) and minimum degradation (< 23%) were obtained in a pH switch loading method from 5.7 to 8, in nanoliposomes (< 50 nm) containing oleyl-peptide, lecithin and Tween-80 (1:1:0.75 mole ratio). The oleyl-peptide did not prove any haemolytic activity (< 1.5%) up to 10-fold of its experimental concentration. The curcumin-loaded liposomes displayed significant reduction in the viabilities of MCF-7 (IC50 3.8 µM) and MDA-MB-468 (IC50 5.4 µM). DISCUSSION AND CONCLUSION: This study indicated potential advantages of the peptide-conjugated liposomes in drug transport to the cancer cells. This feature might be an outcome of probable interactions between the targeted nanoliposomes with the integrin and neuropilin-1 receptors.
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Antineoplásicos Fitogénicos/metabolismo , Neoplasias de la Mama/metabolismo , Curcumina/metabolismo , Portadores de Fármacos , Endocitosis , Integrinas/metabolismo , Nanopartículas , Neuropilina-1/metabolismo , Ácido Oléico/química , Oligopéptidos/metabolismo , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Supervivencia Celular/efectos de los fármacos , Curcumina/química , Curcumina/farmacología , Relación Dosis-Respuesta a Droga , Composición de Medicamentos , Estabilidad de Medicamentos , Femenino , Humanos , Concentración 50 Inhibidora , Liposomas , Células MCF-7 , Oligopéptidos/síntesis química , Factores de TiempoRESUMEN
PURPOSE: Abnormal uterine bleeding (AUB) is one of the prevalent gynecological disorders that cause considerable morbidity and management of that plays an important role in protecting women's health. This review focuses on medicinal plants mentioned by Avicenna, a great Iranian philosopher and physician (A.D. 980-1037), in his book Canon for treatment of AUB. METHODS: Medicinal plants mentioned in Canon for treatment of AUB were elicited and searched in electronic databases including PubMed, Scopus, Google Scholar and Cochrane library to find studies that confirmed their efficacy. Data were collected for the years 1980-2014. RESULTS: The findings included 23 plants belonging to 18 families. Scientific findings have revealed that these plants control AUB through four mechanisms of action including inhibition of inflammatory process, inhibition of prostaglandins production, antiproliferative activity on human cervical cancer cells (HeLa), and estrogenic activity. All of the plants exhibited anti-inflammatory activity in vitro and/or in vivo. Cuscuta chinensis and Portulaca oleracea exhibited estrogenic activity. Boswellia carteri, Lens culinaris, Myrtus communis, Polygonum aviculare, Pistacia lentiscus, and Punica granatum have revealed inhibitory activity on biosynthesis of prostaglandins. Some of the mentioned plants including: Ceratonia siliqua, Cuscuta chinensis, Cuscuta epithymum, Cydonia oblonga, Paeonia sp., Portulaca oleracea, Solanum nigrum, Rumex acetosa and Onopordum acanthium have shown antiproliferative activity on HeLa cells. CONCLUSION: Investigation of traditional Iranian medicine literatures can lead to the identification of effective natural medicines for the management of AUB; however, conclusive confirmation of the efficacy and safety of these treatments needs more evaluations.
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Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Hemorragia Uterina/tratamiento farmacológico , Femenino , Historia Medieval , Humanos , Irán , Medicina Tradicional/historia , Medicina Tradicional/métodos , Extractos Vegetales/historia , Hemorragia Uterina/historiaRESUMEN
In this study, a novel floating, controlled-release and core-shell oral tablet of ketamine hydrochloride (HCl) was produced using a dual extrusion by 3D printing method. A mixture of Soluplus® and Eudragit® RS-PO was extruded by a hot-melt extrusion (HME) nozzle at 150-160 °C to fabricate the tablet shell, while a second nozzle known as a pressure-assisted syringe (PAS) extruded the etamine HCl in carboxymethyl cellulose gel at room temperature (25 °C) inside the shell. The resulting tablets were optimized based on the United States pharmacopeia standards (USP) for solid dosage forms. Moreover, the tablet was characterized using Fourier-transform infrared (FTIR) spectrum, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and buoyancy techniques. The results showed a desired dissolution profile for a 100% infill optimized tablet with total drug release (100%) during 12 h. Weight variation and content uniformity of the tablets achieved the USP requirements. SEM micrographs showed a smooth surface with acceptable layer diameters. According to the FTIR analysis, no interference was detected among peaks. Based on DSC analysis, the crystallinity of ketamine HCl did not change during melt extrusion. In conclusion, the floating controlled-release 3D-printed tablet of ketamine HCl can be a promising candidate for management of refractory depressions and chronic pain. Additionally, the additive manufacturing method enables the production of patient-tailored dosage with tunable-release kinetics for personalized medicine in point-of care setting.
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A critical problem with the use of biomaterial implants is associated with bacterial adhesion on the surface of implants and in turn the biofilm formation. Among different strategies that have been reported to resolve this dilemma, surface design combined with both antiadhesive and antimicrobial properties has proven to be highly effective. Physiochemical properties of polymer brush coatings possess non-adhesive capability against bacterial adhesion and create a niche for further functionalization. The current study aims to evaluate the effect of antibiotics incorporated into the polymer brush on bacterial adhesion and biofilm formation. Brushes made of zwitterionic polymers were synthesized, functionalized with vancomycin via both physical and chemical conjugation, and grafted onto the silicon rubber surfaces. Antibacterial and antiadhesive measurements of designed coated biomaterials were mediated through the use of a parallel plate flow chamber against biofilm growth developed by Staphylococcus aureus and Escherichia coli over a period of 24 h. The analysis of biofilm growth on designed coated biomaterials showed that the pristine coated zwitterionic brushes are significantly resistant to bacterial adhesion and biofilm formation but not in the polymer brush coating incorporated with antibiotics.
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Adhesión Bacteriana , Polímeros , Polímeros/farmacología , Polímeros/química , Antibacterianos/farmacología , Antibacterianos/química , Materiales Biocompatibles/farmacología , Biopelículas , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/química , Propiedades de SuperficieRESUMEN
Nowadays, electrospun fibrous mats are used as drug delivery systems for loading of potential drugs in order to kill cancer cells. In the study, a skin patch for treating melanoma cancer after surgery was made using polycaprolactone and polymetformin microfibers that were loaded with doxycycline (PolyMet/PCL@DOX), an anti-cancer stem cell agent. The morphology, structure, mechanical characteristics, swelling, and porosity of the electrospun microfibers were examined. Drug release andanticancereffectiveness of PolyMet/PCL@DOXwas evaluated against A375 melanoma cancer stem cells using the MTS, Flow cytometry, colony formation and CD44 expression assays. Scanning electron microscopy (SEM) verified the micro fibrous structure with a diameter of about 2.31 µm. The porosity and swelling percentages for microfibers was 73.5 % and 2.9 %, respectively. The tensile strength at the breaking point was equal to 3.84 MPa. The IC50 of PolyMet/PCL@DOX was 7.4 µg/mL. The survival rate of A375 cells after 72 h of PolyMet/PCL@DOX treatment was 43.9 %. The colony formation capacity of A375 cells decreased after PolyMet/PCL@DOX treatment. The level of CD44 expression in the PolyMet/PCL@DOX group decreased compared to the control group. Generally, PolyMet/PCL@DOX microfibers can be a promising candidate as a patch after surgery to eradicate cancer stem cells, effectively.
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Doxiciclina , Liberación de Fármacos , Melanoma , Células Madre Neoplásicas , Poliésteres , Doxiciclina/administración & dosificación , Doxiciclina/farmacología , Doxiciclina/química , Poliésteres/química , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Células Madre Neoplásicas/efectos de los fármacos , Línea Celular Tumoral , Metformina/farmacología , Metformina/administración & dosificación , Metformina/química , Supervivencia Celular/efectos de los fármacos , Receptores de Hialuranos/metabolismo , Porosidad , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
Integrating peptide epitopes in self-assembling materials is a successful strategy to obtain nanovaccines with high antigen density and improved efficacy. In this study, self-assembling peptides containing MAGE-A3/PADRE epitopes were designed to generate functional therapeutic nanovaccines. To achieve higher stability, peptide/polymer hybrid nanoparticles were formulated by controlled self-assembly of the engineered peptides. The nanoparticles showed good biocompatibility to both human red blood- and dendritic cells. Incubation of the nanoparticles with immature dendritic cells triggered immune effects that ultimately activated CD8 + cells. The antigen-specific and IgG antibody responses of healthy C57BL/6 mice vaccinated with the nanoparticles were analyzed. The in vivo results indicate a specific response to the nanovaccines, mainly mediated through a cellular pathway. This research indicates that the immunogenicity of peptide epitope vaccines can be effectively enhanced by developing self-assembled peptide-polymer hybrid nanostructures.
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Nanopartículas , Neoplasias , Ratones , Animales , Humanos , Ratones Endogámicos C57BL , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Péptidos/química , Linfocitos T CD8-positivos , Epítopos/metabolismo , Nanopartículas/químicaRESUMEN
INTRODUCTION: Helicobacter pylori causes stubborn infections and leads to a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. Although antibiotic-based approaches have been widely used against H. pylori, some challenges such as antibiotic resistance are increasing in severity. Therefore, simpler but more effective strategies are needed. AREAS COVERED: In this review, basic information on functionalized and non-functionalized micro/nano biomaterials and routes of administration for H. pylori inhibition are provided in an easy-to-understand format. Afterward, in vitro and in vivo studies of some promising bio-platforms including metal-based biomaterials, biopolymers, small-molecule saccharides, and vaccines for H. pylori inhibition are discussed in a holistic manner. EXPERT OPINION: Functionalized or non-functionalized micro/nano biomaterials loaded with anti-H. pylori agents can show efficient bactericidal activity with no/slight negative influence on the host gastrointestinal microbiota. However, this claim needs to be substantiated with hard data such as assessment of the biopharmaceutical parameters of anti-H. pylori systems and the measurement of diversity/abundance of bacterial genera in the host gastric/gut microbiota before and after H. pylori eradication.
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The rheological properties of wet powder masses used in the preparation of pharmaceutical pellets by extrusion/spheronization were evaluated utilizing capillary and rotational rheometers. A ram extruder was used as a capillary rheometer to construct flow and viscosity curves for each wet mass under different extrusion rates and die geometry. As a result, shear thinning behavior was observed for all wet masses. Among the considered rheological models Power Law and Herschel-Bulkley models fitted well with the experimental results. For the majority of the wet masses, water separation and migration occurred during extrusion which led to uneven water content in the extrudate. The effect of extrusion condition including extrusion speed, die geometry and water content on the occurrence of water separation was investigated and the surface quality of the extrudates was compared. In addition, dynamic rheometry tests were done by a parallel plate rheometer to investigate the viscoelastic properties of the wet masses. The frequency sweep tests showed that as water content of the wet masses decreases storage (G') and loss modulus (Gâ³) increase. The storage modulus values were much higher than those of the loss modulus showing dominated elastic rather than viscous behavior for the wet masses at low deformation rates.
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Composición de Medicamentos/métodos , Excipientes/química , Modelos Químicos , Agua/química , Química Farmacéutica , Formas de Dosificación , Composición de Medicamentos/instrumentación , Almacenaje de Medicamentos , Módulo de Elasticidad , Reología , ViscosidadRESUMEN
In this study melt rheological behavior of lactose-filled polyethylene glycol (PEG) composites as a low melting polymeric carrier for controlled release drugs was investigated using a capillary rheometer. The effect of lactose concentration and process variables such as temperature and ram speed on the flow behavior of PEG has been studied. The composites were found to be shear thinning in behavior when extruded, and the results were well described by power-law model in each case. Stronger shear thinning behavior was observed by raising the filler concentration and decreasing the temperature, while the flow index has been decreased. In all compositions a significant increase in shear viscosity was found by an increase in the filler content. In fact, shear viscosity increased linearly by weight fraction of filler, but there was a dramatic increase after the filler content raised above 20 wt% of lactose which might be the result of the strong interaction among filler particles. Furthermore, decreasing the process temperature resulted in an increase in shear viscosity, and the temperature dependence of shear viscosity decreased as the shear rate increased. The extensional viscosity of composites was calculated in each case. The results showed that the ratio of the extensional viscosity to shear viscosity was in the range of 500-1200.
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Portadores de Fármacos/química , Composición de Medicamentos/métodos , Lactosa/química , Polietilenglicoles/química , Preparaciones de Acción Retardada , Formas de Dosificación , Modelos Teóricos , Polímeros/química , Reología , Resistencia al Corte , Temperatura , Temperatura de Transición , ViscosidadRESUMEN
This paper presents a single-step microfluidic system designed for passive separation of human fresh blood plasma using direct capillary forces. Our microfluidic system is composed of a cylindrical well between upper and lower channel pairs produced by soft photolithography. The microchip was fabricated based on hydrophobicity differences upon suitable cylindrical surfaces using gravitational and capillary forces and lateral migration of plasma and red blood cells. The plasma radiation was applied to attach the polymeric segment (polydimethylsiloxane (PDMS)) to the glass. Meanwhile, Tween 80 was used as a surfactant to increase the hydrophobicity of the lateral channel surfaces. This led to the higher movement of whole blood, including plasma. Fick's law of diffusion was validated for this diffusion transfer, the Navier-Stokes equation was used for the momentum balance, and the Laplace equation was utilized for the dynamics of the mesh. A model with high accuracy using the COMSOL Multiphysics software was created to predict the capillary forces and chip model validation. RBCs (red blood cells) were measured by the H3 cell counter instrument, by which 99% plasma purity was achieved. Practically, 58.3% of the plasma was separated from the blood within 12 min. Correlation between plasma separation results obtained from software and experimental data showed a coefficient of determination equal to 0.9732. This simple, rapid, stable, and reliable microchip can be considered as a promising candidate for providing plasma in point-of-care diagnostics.
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Aim: This study aim to develop doxycycline within the D-α-tocopheryl polyethylene glycol 1000 succinate micelle platform as an anticancer stem cell agent. Materials & methods: The optimized nanomicelle formulation was prepared using the solvent casting method and evaluated through physicochemical and biological characterization. Results: Nanomicelles exhibited mean particle sizes of 14.48 nm (polydispersity index: 0.22) using dynamic light scattering and 18.22 nm using transmission electron micrography. Drug loading and encapsulation efficiency were 2% and 66.73%, respectively. Doxycycline-loaded micelles exhibited sustained release, with 98.5% released in 24 h. IC50 values were 20 µg/ml for free drug and 5 µg/ml for micelles after 48 h of cell exposure. A significant 74% reduction in CD44 biomarker and 100% colony formation inhibition were observed. Conclusion: Doxycycline in hemo/biocompatible nanomicelles holds potential for ovarian cancer stem cell therapy.
Cancer, a global leading cause of death, has a significant impact on human health. Among the various types of cancer, ovarian cancer ranks as the seventh most prevalent, posing a significant threat to women and contributing significantly to deaths in this population. Recent studies have highlighted the importance of targeting cancer stem cells to enhance the effectiveness of cancer treatments and prevent tumor relapse. Cancer stem cells are cells that can differentiate into different cell types in a tumor, driving the growth and spread of cancer. Over the past few decades, certain antibiotics, including doxycycline, have emerged as potent and selective anticancer stem cell agents by specifically targeting mitochondrial biogenesis. In line with this, the authors developed a doxycycline-loaded micelle delivery system. Micelles are spheres made of a single layer of a type of fat called phospholipids; they have been combined with drugs to increase the successful delivery and effectiveness of that drug. This research revealed that this micelle formulation demonstrated a fourfold increase in efficacy against ovarian cancer stem cells compared with free antibiotics. Moreover, it efficiently reduced colony formation and CD44 biomarker levels among the stem cells, indicating damage to cancer stem cells. These findings underscore the potential of this doxycycline-loaded micelle system as a promising approach for eradicating ovarian cancer stem cells and improving therapeutic outcomes.
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Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Micelas , Doxiciclina/farmacología , Línea Celular Tumoral , Polietilenglicoles/química , Antineoplásicos/química , Neoplasias Ováricas/tratamiento farmacológico , Vitamina E/química , Células Madre Neoplásicas , Succinatos , Tamaño de la Partícula , Portadores de Fármacos/químicaRESUMEN
Zoledronic acid (ZA) is known as a potent bisphosphonate in osteogenic differentiation, but at high doses, it possesses toxic effects and causes decreased proliferation and differentiation of osteoblasts. Therefore, encapsulation of ZA into nanoparticles and control of its release is expected to promote differentiation of stem cells into osteoblasts. The present work aimed to develop a simple method for synthesis of monodisperse ZA-loaded chitosan (CS) nanoparticles. In this regard, we proposed a microfluidic synthesis of nanoparticles through the ionic cross-linking of CS in the presence of ZA without a crosslinker. The main advantages of these microfluidic generated nanoparticles were narrow size distribution and fine spherical shape. Conversely, the nanoparticles that were synthesized using a bulk mixing method had an irregular shape with a broad size distribution. Real-time PCR assay as well as alizarin red staining were used to evaluate the in-vitro osteogenic potential of the nanoparticles. The results indicated that the controlled release of ZA from the microfluidic system generated uniform nanoparticles, improving the osteogenic differentiation of mesenchymal stem cells. Additionally, this microfluidic device provided the well-controlled synthesis of novel nanoparticles with a modified CS macromolecular polymer for targeted drug delivery systems.
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Quitosano , Células Madre Mesenquimatosas , Nanopartículas , Osteogénesis , Ácido Zoledrónico/farmacología , Quitosano/farmacología , Microfluídica , Diferenciación CelularRESUMEN
INTRODUCTION: Helicobacter pylori is a widespread helical Gram-negative bacterium, which causes a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and survives in the inhospitable microenvironment, by adapting to this hostile milieu. AREAS COVERED: In this extensive review, we describe conventional antibiotic treatment regimens used against H. pylori including, empirical, tailored, and salvage therapies. Then, we present state-of-the-art information about reasons for treatment failure against H. pylori. Afterward, the latest advances in the use of probiotic bacteria against H. pylori infection are discussed. Finally, we propose a polymeric bio-platform to provide efficient delivery of probiotics for H. pylori infection. EXPERT OPINION: For effective probiotic delivery systems, it is necessary to avoid the early release of probiotics at the acidic stomach pH, to protect them against enzymes and antimicrobials, and precisely target H. pylori bacteria which have colonized the antrum area of the stomach (basic pH).
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Infecciones por Helicobacter , Helicobacter pylori , Úlcera Péptica , Probióticos , Neoplasias Gástricas , Humanos , Infecciones por Helicobacter/microbiología , Úlcera Péptica/complicaciones , Úlcera Péptica/microbiología , Neoplasias Gástricas/microbiología , Insuficiencia del Tratamiento , Microambiente TumoralRESUMEN
An extended-release tablet of tacrolimus as once-daily dosing was fabricated using 3D printing technology. It was developed by combining two 3D-printing methods in parallel. Indeed, an optimized mixture of PVA, sorbitol, and magnesium stearate as a shell compartment was printed through a hot-melt extrusion (HME) nozzle while an HPMC gel mixture of the drug in the core compartment was printed by a pressure-assisted micro-syringe (PAM). A 3D-printed tablet with an infill of 90% was selected as an optimized formula upon the desired dissolution profile, releasing 86% of the drug at 12 h, similar to the commercial one. The weight variation, friability, hardness, assay, and content uniformity determination met USP requirements. A microbial evaluation showed that the 3D-printed tablet does not support microbial growth. SEM analysis showed smooth surfaces with multiple deposited layers. No peak interference appeared based on FTIR analysis. No decomposition of the polymer and drug was observed in the printing temperature, and no change in tacrolimus crystallinity was detected based on TGA and DSC analyses, respectively. The novel, sTable 3D-printed tablet, fabricated using controllable additive manufacturing, can quickly provide tailored dosing with specific kinetic release for personalized medicine at the point-of-care.
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Inflammatory bowel disease (IBD) is a gastrointestinal disorder, affecting about several million people worldwide. Current treatments fail to adequately control some clinical symptoms in IBD patients, which can adversely impact the patient's quality of life. Hence, the development of new treatments for IBD is needed. Due to their unique properties such as biocompatibility and sustained release of a drug, biomaterials-based drug delivery systems can be regarded as promising candidates for IBD treatment. It is noteworthy that considering the pathophysiological changes occurred in the gastrointestinal tract of IBD patients, especially changes in pH, surface charge, the concentration of reactive oxygen species, and the expression of some biomolecules at the inflamed colon, can help in the rational design of biomaterials-based drug delivery systems for efficient management of IBD. Here, we discuss about targeting these pathophysiological changes using biomaterials-based drug delivery systems, which can provide important clues to establish a strategic roadmap for future studies.
RESUMEN
Streptococcal pharyngitis is mainly caused by Streptococcus pyogenes (GAS), which if left untreated can lead to rheumatic heart disease. The accurate diagnosis of streptococcal pharyngitis is a challenge for clinicians because several symptoms of streptococcal pharyngitis are similar to viral pharyngitis. There are some commercially available biosensors for the rapid diagnosis of streptococcal pharyngitis. Nevertheless, they are not widely used by physicians, mainly because of their high price and dependence on the instrument. Serotype M1 GAS is the most prevalent cause of streptococcal pharyngitis and binds to H-1 antigen, a sugar code found on oral epithelial cells. Here, we present a nanobiosensor based on aggregation of H-1 antigen-conjugated gold nanoparticles for the rapid, qualitative, and quantitative detection of M1 GAS, which is inspired by the sugar code-lectin interaction. It is noteworthy that M1 GAS was detected in a wide concentration range (1 × 103-1×106 CFU/ml) with a linear response and a short detection time of 20 min. Good reproducibility, easy-to-use, and relatively low production cost are among other attractive features of this nanobiosensor. This work provides a strategic roadmap for developing a new generation of biosensors via targeting the sugar code-lectin interaction in future studies.