ABSTRACT
Purpose: Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer. Methods: We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system. Results: OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was >65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (**p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo. Conclusion: Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer.
Subject(s)
Micelles , Ovarian Neoplasms , Phthalazines , Piperazines , Polyethylene Glycols , Polyvinyls , Sirolimus , Vitamin E , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Piperazines/chemistry , Piperazines/pharmacology , Polyethylene Glycols/chemistry , Humans , Animals , Cell Line, Tumor , Vitamin E/chemistry , Vitamin E/pharmacology , Sirolimus/chemistry , Sirolimus/pharmacology , Sirolimus/administration & dosage , Sirolimus/pharmacokinetics , Phthalazines/chemistry , Phthalazines/pharmacology , Phthalazines/administration & dosage , Phthalazines/pharmacokinetics , Polyvinyls/chemistry , Polyvinyls/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Mice , Drug Carriers/chemistry , Xenograft Model Antitumor Assays , Mice, Nude , Mice, Inbred BALB C , Cell Survival/drug effectsABSTRACT
Electrospinning is a facile popular method for the creation of nano-micro fibers tissue engineering scaffolds. Here, polycaprolactone (PCL)/collagen (COL): polyvinyl pyrrolidone (PVP) scaffolds (PCL/COL: PVP) were fabricated for bone regeneration. Various concentrations of Cephalexin (CEF) (0.5, 1, 1.5 wt. %) were added to PCL/COL: PVP scaffold to provide an antibacterial scaffold, and different concentrations of hydroxyapatite (HA) (1, 2, 5 wt. %) was electrospray on the surface of the scaffolds. The PCL/COL: PVP scaffold contained 1.5% CEF and coated with 2% HA was introduced as the best sample and in-vitro tests were performed on this scaffold based on the antibacterial and MTT test results. Morphology observations demonstrated a bead-free uniform combined nano-micro fibrous structure. Fourier transform infrared spectroscopy and X-ray diffraction tests confirmed the successful formation of the scaffolds and the wettability, swelling, and biodegradability evaluations of the scaffolds confirmed the hydrophilicity nature of the scaffold with high swelling properties and suitable biodegradation ratio. The scaffolds supported cell adhesion and represented high alkaline phosphatase activity. CEF loading led to antibacterial properties of the designed scaffolds and showed a suitable sustained release rate within 48 h. It seems that the electrospun PCL/COL: PVP scaffold loaded with 1.5% CEF and coated with 2% HA can be useful for bone regeneration applications that need further evaluation in the near future.
Subject(s)
Durapatite , Polyvinyls , Durapatite/chemistry , Polyvinyls/pharmacology , Cephalexin/pharmacology , Tissue Scaffolds/chemistry , Collagen/chemistry , Polyesters/chemistry , Tissue Engineering/methods , Bone Regeneration , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Cell ProliferationABSTRACT
Electroactive smart materials play an important role for tissue regenerative applications. Poly(vinylidene fluoride) (PVDF) is a specific subtype of piezoelectric electroactive material that generates electrical potential upon mechanical stimulation. This work focuses on the application of piezoelectric PVDF films for neural differentiation. Human neural precursor cells (hNPCs) are cultured on piezoelectric poled and non-poled ß-PVDF films with or without a pre-coating step of poly-d-lysine and laminin (PDL/L). Subsequently, hNPCs differentiation into the neuronal lineage is assessed (MAP2+ and DCX+ ) under static or dynamic (piezoelectric stimulation) culture conditions. The results demonstrate that poled and coated ß-PVDF films induce neuronal differentiation under static culture conditions which is further enhanced with mechanical stimulation. In silico calculations of the electrostatic potential of different domains of laminin, highlight the high polarity of those domains, which shows a clear preference to interact with the varying surface electric field of the piezoelectric material under mechanical stimulation. These interactions might explain the higher neuronal differentiation induced by poled ß-PVDF films pre-coated with PDL/L under dynamic conditions. Our results suggest that electromechanical stimuli, such as the ones induced by piezoelectric ß-PVDF films, are suitable to promote neuronal differentiation and hold great promise for the development of neuroregenerative therapies.
Subject(s)
Laminin , Neural Stem Cells , Humans , Electricity , Laminin/pharmacology , Polyvinyls/pharmacology , Electric StimulationABSTRACT
Clinical use of human pluripotent stem cells (hPSCs) is hampered by the technical limitations of their expansion. Here, we developed a chemically synthetic culture substrate for human pluripotent stem cell attachment and maintenance. The substrate comprises a hydrophobic polyvinyl butyral-based polymer (PVB) and a short peptide that enables easy and uniform coating of various types of cell culture ware. The coated ware exhibited thermotolerance, underwater stability and could be stored at room temperature. The substrate supported hPSC expansion in combination with most commercial culture media with an efficiency similar to that of commercial substrates. It supported not only the long-term expansion of examined iPS and ES cell lines with normal karyotypes during their undifferentiated state but also directed differentiation of three germ layers. This substrate resolves major concerns associated with currently used recombinant protein substrates and could be applied in large-scale automated manufacturing; it is suitable for affordable and stable production of clinical-grade hPSCs and hPSC-derived products.
Subject(s)
Cell Culture Techniques/methods , Cell Differentiation/drug effects , Cell Self Renewal/drug effects , Human Embryonic Stem Cells/cytology , Induced Pluripotent Stem Cells/cytology , Peptides/pharmacology , Polyvinyls/pharmacology , Tissue Scaffolds/chemistry , Cell Adhesion/drug effects , Cell Line , Human Embryonic Stem Cells/drug effects , Human Embryonic Stem Cells/metabolism , Humans , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Peptides/metabolism , Polyvinyls/metabolismABSTRACT
At present, membrane fouling is a thorny issue that limits the development of polyvinylidene fluoride (PVDF) composite membrane, which seriously affects its separation performance and service lifespan. Herein, an imidazole-functionalized graphene oxide (Im-GO) with hydrophilicity and antibacterial performance was synthesized, and it was used as a modifier to improve the anti-organic fouling and antibacterial properties of PVDF membrane. The anti-organic fouling test showed that the maximum flux recovery ratios against bovine serum albumin and humic acid were 88.9% and 94.5%, respectively. Conspicuously, the grafted imidazole groups could effectively prevent the bacteria from growing on the membrane surface. It was gratifying that the antibacterial modifier Im-GO was almost not lost from the hybrid membranes even by the ultrasonic treatment, which was different from the conventional release-killing antibacterial agents. Owing to the long-term anti-organic fouling and antibacterial properties, Im-GO/PVDF hybrid membranes exhibit a great application potential in the fields of rough separation and concentration of biomedical products.
Subject(s)
Membranes, Artificial , Ultrafiltration , Anti-Bacterial Agents/pharmacology , Fluorocarbon Polymers , Graphite , Imidazoles/pharmacology , Polyvinyls/pharmacologyABSTRACT
The predominant impediments to cutaneous wound regeneration are hemorrhage and bacterial infections that lead to extensive inflammation with lethal impact. We thus developed a series of composite sponges based on polyvinyl alcohol (PVA) inspired by marjoram essential oil and kaolin (PVA/marjoram/kaolin), adopting a freeze-thaw method to treat irregular wounds by thwarting lethal bleeding and microbial infections. Microstructure analyses manifested three-dimensional interconnected porous structures for PVA/marjoram/kaolin. Additionally, upon increasing marjoram and kaolin concentrations, the pore diameters of the sponges significantly increased, recording a maximum of 34 ± 5.8 µm for PVA-M0.5-K0.1. Moreover, the porosity and degradation properties of PVA/marjoram/kaolin sponges were markedly enhanced compared with the PVA sponge with high swelling capacity. Furthermore, the PVA/marjoram/kaolin sponges exerted exceptional antibacterial performance against Escherichia coli and Bacillus cereus, along with remarkable antioxidant properties. Moreover, PVA/marjoram/kaolin sponges demonstrated significant thrombogenicity, developing high thrombus mass and hemocompatibility, in addition to their remarkable safety toward fibroblast cells. Notably, this is the first study to our knowledge investigating the effectiveness of marjoram in a polymeric carrier for prospective functioning as a wound dressing. Collectively, the findings suggest the prospective usage of the PVA-M0.5-K0.1 sponge in wound healing for hemorrhage and bacterial infection control.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Bandages , Hemostatics/pharmacology , Origanum/chemistry , Animals , Anti-Bacterial Agents/chemistry , Antioxidants/analysis , Antioxidants/chemistry , Hemostatics/chemistry , Humans , Kaolin/chemistry , Materials Testing , Mice , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , NIH 3T3 Cells , Plant Extracts/chemistry , Plant Extracts/pharmacology , Polyvinyl Alcohol/chemistry , Polyvinyls/chemistry , Polyvinyls/pharmacology , Spectroscopy, Fourier Transform Infrared , ThermogravimetryABSTRACT
The efficiency of filtration membranes is substantially lowered by bacterial attachments and potential fouling processes, which reduce their durability and lifecycle. The antibacterial and antifouling properties exhibited by the added materials play a substantial role in their application. We tested a material poly(vinylidene fluoride)-co-hexafluoropropylene (PDVF-co-HFP) based on an electrospun copolymer, where an agent was incorporated with a small amount of ester of glycerol consecutively with caprylic, capric, and lauric acids. Each of these three materials differing in the esters (1-monoacylglycerol, 1-MAG) used was prepared with three weighted concentrations of 1-MAG (1, 2, and 3 wt %). The presence of 1-MAG with an amphiphilic structure resulted in the hydrophilic character of the prepared materials that contributed to the filtration performance. The tested materials (membranes) were characterized with rheological, optical (scanning electron microscopy, SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and other methods to evaluate antibacterial and antifouling activities. The pure water flux was 6 times higher than that of the neat PVDF-co-HFP membrane when the added 1-MAG attained only 1 wt %. It was experimentally shown that the PVDF-co-HFP/1-MAG membrane with high wettability improved antibacterial activity and antifouling ability. This membrane is highly promising for water treatment due to the safety of antibacterial 1-MAG additives.
Subject(s)
Anti-Bacterial Agents/pharmacology , Fluorocarbon Polymers/pharmacology , Monoglycerides/pharmacology , Nanofibers/chemistry , Polyvinyls/pharmacology , Anti-Bacterial Agents/chemistry , Biofilms/drug effects , Biofouling/prevention & control , Escherichia coli/drug effects , Escherichia coli/physiology , Filtration/instrumentation , Fluorocarbon Polymers/chemistry , Membranes, Artificial , Microbial Sensitivity Tests , Monoglycerides/chemistry , Polyvinyls/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , WettabilityABSTRACT
Disinfecting pathogenic contaminated water rapidly and effectively on sites is one of the critical challenges at point-of-use (POU) situations. Currently available technologies are still suffering from irreversible depletion of disinfectants, generation of toxic by-products, and potential biofouling problems. Herein, we developed a chlorine rechargeable biocidal nanofibrous membrane, poly(acrylonitrile-co-5-methyl-5-(4'-vinylphenyl)imidazolidine-2,4-dione) (P(AN-VAPH)), via a combination of a free radical copolymerization reaction and electrospun technology. The copolymer exhibits good electrospinnability and desirable mechanical properties. Also, the 5-methyl-5-(4'-vinylphenyl)imidazolidine-2,4-dione (VAPH) moieties containing unique hydantoin structures are able to be chlorinated and converted to halamine structures, enabling the P(AN-VAPH) nanofibrous membrane with rapid and durable biocidal activity. The chlorinated P(AN-VAPH) nanofibrous membranes showed intriguing features of unique 3D morphological structures with large specific surface area, good mechanical performance, rechargeable chlorination capacity (>5000 ppm), long-term durability, and desirable biocidal activity against both bacteria and viruses (>99.9999% within 2 min of contact). With these attributes, the chlorinated P(AN-VAPH) membranes demonstrated promising disinfecting efficiency against concentrated bacteria-contaminated water during direct filtration applications with superior killing capacity and high flowing flux (5000 L m-2 h-1).
Subject(s)
Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Disinfectants/pharmacology , Hydantoins/pharmacology , Membranes, Artificial , Nanofibers/chemistry , Acrylic Resins/chemical synthesis , Acrylic Resins/pharmacology , Anti-Bacterial Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Bacteriophage T7/drug effects , Disinfectants/chemical synthesis , Disinfection/instrumentation , Escherichia coli/drug effects , Filtration/instrumentation , Hydantoins/chemical synthesis , Listeria/drug effects , Microbial Sensitivity Tests , Polyvinyls/chemical synthesis , Polyvinyls/pharmacology , Water Purification/instrumentationABSTRACT
Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti3 C2 -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti3 C2 and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.
Subject(s)
Acute Kidney Injury/drug therapy , Antioxidants/pharmacology , Oxidation-Reduction/drug effects , Polyvinyls/pharmacology , Pyrrolidines/pharmacology , Titanium/pharmacology , Acute Kidney Injury/metabolism , Apoptosis/drug effects , Humans , Kidney/drug effects , Kidney/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effectsABSTRACT
We demonstrate an intrinsic antitumor effect of polymer nanoparticles (P-NPs), which could re-program tumor-associated macrophages to pro-inflammatory phenotype. The intrinsic effect of P-NPs on macrophage repolarization and its combination with other therapies provide new ideas for drug delivery, macrophage regulation and immunotherapy in cancer treatment.
Subject(s)
Antineoplastic Agents/pharmacology , Macrophage Activation/drug effects , Macrophages/drug effects , Maleates/pharmacology , Nanoparticles/chemistry , Polystyrenes/pharmacology , Polyvinyls/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Maleates/chemistry , Maleates/toxicity , Mice , Nanoparticles/toxicity , Polystyrenes/chemistry , Polystyrenes/toxicity , Polyvinyls/chemistry , Polyvinyls/toxicityABSTRACT
The foodborne pathogen Listeria monocytogenes is able to survive across a wide range of intra- and extra-host environments by appropriately modulating gene expression patterns in response to different stimuli. Positive Regulatory Factor A (PrfA) is the major transcriptional regulator of virulence gene expression in L. monocytogenes. It has long been known that activated charcoal is required to induce the expression of PrfA-regulated genes in complex media, such as Brain Heart Infusion (BHI), but not in chemically defined media. In this study, we show that the expression of the PrfA-regulated hly, which encodes listeriolysin O, is induced 5- and 8-fold in L. monocytogenes cells grown in Chelex-treated BHI (Ch-BHI) and in the presence of activated charcoal (AC-BHI), respectively, relative to cells grown in BHI medium. Specifically, we show that metal ions present in BHI broth plays a role in the reduced expression of the PrfA regulon. In addition, we show that expression of hly is induced when the levels of bioavailable extra- or intercellular iron are reduced. L. monocytogenes cells grown Ch-BHI and AC-BHI media showed similar levels of resistance to the iron-activated antibiotic, streptonigrin, indicating that activated charcoal reduces the intracellular labile iron pool. Metal depletion and exogenously added glutathione contributed synergistically to PrfA-regulated gene expression since glutathione further increased hly expression in metal-depleted BHI but not in BHI medium. Analyses of transcriptional reporter fusion expression patterns revealed that genes in the PrfA regulon are differentially expressed in response to metal depletion, metal excess and exogenous glutathione. Our results suggest that metal ion abundance plays a role in modulating expression of PrfA-regulated virulence genes in L. monocytogenes.
Subject(s)
Bacterial Toxins/genetics , Charcoal/pharmacology , Heat-Shock Proteins/genetics , Hemolysin Proteins/genetics , Listeria monocytogenes/growth & development , Peptide Termination Factors/genetics , Polystyrenes/pharmacology , Polyvinyls/pharmacology , Bacterial Proteins/genetics , Culture Media/chemistry , Gene Expression Regulation, Bacterial/drug effects , Glutathione/metabolism , Iron/chemistry , Listeria monocytogenes/drug effects , Listeria monocytogenes/genetics , Listeria monocytogenes/pathogenicity , Streptonigrin/pharmacology , Virulence/drug effects , Zinc/chemistryABSTRACT
Cell adhesion-mediated piezoelectric stimulation provides a noninvasive method for in situ electrical regulation of cell behavior, offering new opportunities for the design of smart materials for tissue engineering and bioelectronic medicines. In particular, the surface potential is mainly dominated by the inherent piezoelectricity of the biomaterial and the dynamic adhesion state of cells. The development of an efficient and optimized material interface would have important implications in cell regulation. Herein, we modified the surface of poled poly(vinylidene fluoride) (PVDF) membranes through polymerization of dopamine and investigated their influence on cell adhesion and electromechanical self-stimulation. Our results demonstrated that mesenchymal stem cells seeded on the poled PVDF membrane exhibited stronger cell spreading and adhesion. Meanwhile, the surface modification through polydopamine significantly improved the hydrophilicity of the samples and contributed to the formation of cell actin bundles and maturation of focal adhesions, which further positively modulated cell piezoelectric self-stimulation and induced intracellular calcium transients. Combining with theoretical simulations, we found that the self-stimulation was enhanced mainly due to the increase of the adhesion site and adhesion force magnitude. These findings provide new insights for probing the cell regulation mechanism on piezoelectric substrates, offering more opportunities for the rational design of piezoelectric biomaterial interfaces for biomedical engineering.
Subject(s)
Cell Adhesion/drug effects , Indoles/chemistry , Membranes, Artificial , Polymers/chemistry , Polyvinyls/chemistry , Polyvinyls/pharmacology , Animals , Calcium/metabolism , Electrochemistry , Hydrophobic and Hydrophilic Interactions , Intracellular Space/drug effects , Intracellular Space/metabolism , Mechanical Phenomena , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , RatsABSTRACT
OBJECTIVES: Current treatment for autonomic dysreflexia (AD) involves rupturing a liquid-filled soft capsule of nifedipine to aid rapid drug release and absorption, however, this application is not covered under the manufacturer's license. The objective of the current work was to design a rapidly dissolving solid dosage formulation for the treatment of AD as an alternative to the off-license "bite and swallow" use of currently available commercial products. METHODS: Amorphous solid dispersions (ASDs) of nifedipine were prepared by spray-drying using three different polymers: hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone (PVP) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus), at a 15% w/w drug loading and were formulated and compressed into tablets. Dissolution testing was performed in the paddle dissolution apparatus using either a monophasic or biphasic medium. KEY FINDINGS: The PVP-nifedipine ASD tablets exhibited rapid dissolution, with 35% of the total nifedipine dose dissolving within 15 min in the monophasic dissolution medium. The HPMC-nifedipine ASD exhibited a very slow dissolution, while the Solupus-nifedipine system exhibited no nifedipine release over 120 min. When tested in the biphasic dissolution medium, the PVP-nifedipine ASD tablets exhibited a release profile comparable to that of the pre-split/ruptured nifedipine soft capsule product. CONCLUSIONS: This study demonstrates that a nifedipine-PVP ASD is a promising formulation strategy in the treatment of AD.
Subject(s)
Autonomic Dysreflexia/drug therapy , Drug Compounding/methods , Drug Liberation , Nifedipine/pharmacology , Solubility , Calcium Channel Blockers/pharmacology , Chemistry Techniques, Synthetic/methods , Excipients/pharmacology , Humans , Hypromellose Derivatives/pharmacology , Polyethylene Glycols/pharmacology , Polyvinyls/pharmacology , Pyrrolidines/pharmacology , Spray DryingABSTRACT
AIMS: To compare the effectiveness and safety of polypropylene (PP) and polyvinylidene fluoride (PVDF) transobturator tapes (TOT) for the treatment of female stress urinary incontinence (SUI). METHODS: This is a multicentre randomized trial. Women with SUI or stress-predominant mixed urinary incontinence and scheduled for a TOT procedure were randomized to PP or PVDF slings. The primary outcome was 1-year cure or improvement rate using composite criteria. Complications were also compared. Relationships with outcomes were analyzed using multivariable logistic regressions models. RESULTS: From April 2016 to January 2018 285 participants were randomized. PP and PVDF slings showed similar high cure or improvement rate (91.0% vs. 95.6%, p = .138). Improvement in validated questionnaires was also similar. PVDF slings were associated with a lower rate of de novo urgency incontinence (adjusted odds ratio = 0.35; 95% confidence interval = 0.15-0.80). We found no statistical differences in complications rates, although a higher incidence of long-term pain events were observed in the PP group. The study is underpowered to find differences in specific complications owing to the low number of events. CONCLUSION: PP and PVDF TOTs are equally effective, although PVDF is associated with fewer cases of de novo urgency incontinence. Further studies are needed to give robust conclusions on safety profiles.
Subject(s)
Polypropylenes/therapeutic use , Polyvinyls/therapeutic use , Urinary Incontinence/drug therapy , Urinary Incontinence/therapy , Urologic Surgical Procedures/methods , Aged , Female , Humans , Male , Middle Aged , Polypropylenes/pharmacology , Polyvinyls/pharmacology , Surveys and Questionnaires , Treatment Outcome , Urinary Incontinence, StressABSTRACT
Recently, extreme ultraviolet (EUV) radiation has been increasingly used to modify polymers. Properties such as the extremely short absorption lengths in polymers and the very strong interaction of EUV photons with materials may play a key role in achieving new biomaterials. The purpose of the study was to examine the impact of EUV radiation on cell adhesion to the surface of modified polymers that are widely used in medicine: poly(tetrafluoroethylene) (PTFE), poly (vinylidene fluoride) (PVDF), and poly-L-(lactic acid) (PLLA). After EUV surface modification, which has been performed using a home-made laboratory system, changes in surface wettability, morphology, chemical composition and cell adhesion polymers were analyzed. For each of the three polymers, the EUV radiation differently effects the process of endothelial cell adhesion, dependent of the parameters applied in the modification process. In the case of PVDF and PTFE, higher cell number and cellular coverage were obtained after EUV radiation with oxygen. In the case of PLLA, better results were obtained for EUV modification with nitrogen. For all three polymers tested, significant improvements in endothelial cell adhesion after EUV modification have been demonstrated.
Subject(s)
Cell Adhesion , Endothelial Cells/physiology , Microvessels/physiology , Polyesters/pharmacology , Polytetrafluoroethylene/pharmacology , Polyvinyls/pharmacology , Ultraviolet Rays , Cells, Cultured , Endothelial Cells/drug effects , Humans , Microvessels/drug effects , Polyesters/chemistry , Polyesters/radiation effects , Polytetrafluoroethylene/chemistry , Polytetrafluoroethylene/radiation effects , Polyvinyls/chemistry , Polyvinyls/radiation effects , Surface Properties , WettabilityABSTRACT
OBJECTIVE: The main objective of this work was to formulate a nanodispersion containing grape seed extract and analyzed its release profile, antioxidant potential of the prepared formulations. METHODS: The grape seed extract (GSE) containing proanthocyanidins (PC's) has been dispersed in polymer matrix soluplus (SOLU) by the freeze-drying method. The morphological analysis was carried out using atomic force microscopy (AFM), scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). The in-vitro release of the nanodispersion formulations was evaluated by simulated intestinal fluid (SIF). The antioxidant activity of GSE and the formulation were evaluated by employing various in-vitro assays such as 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2, 2-diphenyl-1- picrylhydrazyl (DPPH), Ferric reducing antioxidant power (FRAP) and peroxidation inhibiting activity. RESULTS: The formulation FIII (1:5) resulted in a stable formulation with a higher loading efficiency of 95.36%, a particle size of 69.90 nm, a polydispersity index of 0.154 and a zeta potential value of -82.10 mV. The antioxidant efficiency of GSE-SOLU evaluated by DPPH was found to be 96.7%. The ABTS and FRAP model exhibited a dose-dependent scavenging activity. Linoleic model of FIII formulation and GSE exhibited a 66.14 and 86.58% inhibition respectively at 200 µg/l. CONCLUSIONS: The main reason for excellent scavenging activity of the formulations can be attributed to the presence of monomeric, dimeric, oligomeric procyanidins and the phenolic group. The present work denotes that GSE constitutes a good source of PC's and will be useful in the prevention and treatment of free radical related diseases.
Subject(s)
Antioxidants/pharmacology , Grape Seed Extract/pharmacology , Polyethylene Glycols/pharmacology , Polyvinyls/pharmacology , Grape Seed Extract/chemistry , Polyethylene Glycols/chemistry , Polyvinyls/chemistryABSTRACT
Carotid cavernous fistula (CCF) is a rare disease caused by abnormal communications between the internal carotid artery (direct fistula) or meningeal branches of the external carotid artery (indirect fistula) and the cavernous sinus (CS). Trauma is the most common cause of CCF. The clinical presentation of CCF is closely related to the venous drainage pattern. Orbital and neuro-ophthalmological symptoms are the most common clinical presentation of CCF with drainage through the superior ophthalmic vein (SOV). Endovascular embolization by arterial or venous approaches is the most common management of CCF. Transvenous embolization using detachable coils and ethylene-vinyl alcohol copolymer (EVOH) is an alternative method for the treatment of CCF. Endovascular embolization offers different options to treat CCF by minimally invasive approach decreasing morbidity and residual fistulas. The purpose of this article is to report our treatment experiences via the inferior petrosal sinus (IPS), and immediate-term outcomes of endovascular embolization of CCF by using detachable coils and EVOH.
Subject(s)
Carotid-Cavernous Sinus Fistula/therapy , Cavernous Sinus/drug effects , Embolization, Therapeutic/methods , Polyvinyls/pharmacology , Carotid-Cavernous Sinus Fistula/diagnosis , Female , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
In this in vitro study, the effect of the application of tooth bleaching products in human enamel was evaluated using polarized Raman microscopy, particle induced gamma-ray emission (PIGE) and Vickers Hardness test. Due to their acidic nature, teeth whitening products are associated with changes in enamel mineralization. Consequently, products have appeared in the market that promote the incorporation of fluorine in order to decrease the solubility of the hydroxyapatite in enamel and prevent demineralization. This way, four commercial products with different active principle concentrations: 16% carbamide peroxide (Opalescence PF® and VivaStyle®) or 6% hydrogen peroxide (Opalescence Go PF® and VivaStyle Paint On®) and presence or not of fluorine were compared. The information on the crystalline state of the enamel was provided by the determination of the depolarization ratio of the symmetric stretching band of phosphate (at 959 cm-1). Furthermore, the content and uptake of F was evaluated using PIGE in the two fluorinated products as well as in one negative control group. In order to evaluate the microhardness of enamel by means of Vickers test, another group of polished samples was prepared (using Opalescence PF®) and evaluated. Conversely to what could be expected, the obtained results determined a statistically significant decrease of depolarization ratio, leading to an increase of mineralization after the application of the bleaching products, except for VivaStyle®. For this group, no significant variation was obtained before-after treatment, most likely due to the acidity of the product (pH = 5.8). Additionally, an increase of concentration of F in the dental tissues was determined for the fluorinated products. On the other hand, enamel polishing, required for the application of the Vickers test, led to increased susceptibility to erosion, resulting in decreased hardness and an increased enamel depolarization ratio.
Subject(s)
Bleaching Agents/pharmacology , Hydrogen Peroxide/pharmacology , Tooth Bleaching/methods , Carbamide Peroxide/pharmacology , Dental Enamel/drug effects , Drug Combinations , Drug Evaluation , Fluorine/pharmacokinetics , Gamma Rays , Halogenation , Humans , Hydrogen-Ion Concentration , Microscopy , Peroxides/pharmacology , Polyvinyls/pharmacology , Spectrum Analysis, Raman/instrumentation , Spectrum Analysis, Raman/methods , Urea/analogs & derivatives , Urea/pharmacologyABSTRACT
AIM: Arteriovenous malformation (AVM) embolisation is in peril after the ARUBA trial. Advancements that are needed to reduce procedural risk are better control and visualisation during micro-catheter injection of liquid embolic material. The injectability, radiographic visualisation, mechanical stability and biocompatibility of the embolic agent Fe3O4-EVOH was evaluated in an in vivo swine AVM model. METHODS: The swine AVM model is the rete mirabile (RM). Nine swine AVM models were embolised with the embolic agent Fe3O4-EVOH by using a 1.5 F micro-catheter. Procedure times, embolisation success (deï¬ned as complete embolisation of the nidus), volume of embolic agent and histopathology were assessed. RESULTS: Six swine underwent embolisation of one side rete, and three underwent embolisation of both sides. We did not experience any technical complication during embolisation of each rete. The micro-catheter was easy to retrieve. Fluoroscopic visualisation of the Fe3O4-EVOH cast was adequate. The mean embolisation time for each RM was 7.5 minutes. The median volume of the embolic agent for each RM was 0.52 mL. At one, four and eight weeks following injection, microscopic and histological analysis demonstrated minimal inflammatory changes in the perivascular tissues and permanent occlusion of the embolised vasculature. CONCLUSION: Fe3O4-EVOH embolic agent is an effective endovascular occlusion material, providing the initial in vivo characteristics of stability and biocompatibility.
Subject(s)
Cerebral Angiography , Embolization, Therapeutic/methods , Ferrosoferric Oxide/pharmacology , Intracranial Arteriovenous Malformations/diagnostic imaging , Intracranial Arteriovenous Malformations/therapy , Polyvinyls/pharmacology , Animals , Biocompatible Materials , Disease Models, Animal , SwineABSTRACT
Carvedilol (CAR), a ß-adrenoceptor and α1-receptor blocker, has pH-dependent solubility, which greatly limits its oral bioavailability. In this work, a precipitation inhibitor-based self-nanoemulsifying drug delivery system (PI-SNEDDS) was developed by employing Soluplus and Poloxamer 407 to improve drug dissolution and to inhibit drug precipitation in the gastrointestinal tract. In vitro phase distribution and in vivo dissolution studies indicated that PI-SNEDDS significantly increased drug content in the oil phase of the nanoemulsions in the stomach and greatly inhibited the subsequent precipitation of CAR in the intestine compared with the carvedilol self-nanoemulsifying drug delivery system (CAR SNEDDS) and the carvedilol tablets. Moreover, a 1.56-fold increase in the relative bioavailability of CAR was observed for the CAR PI-SNEDDS (397.41%) compared to a CAR SNEDDS (254.09%) with commercial capsules as a reference. Therefore, our developed PI-SNEDDS is a promising vehicle for improving the dissolution and bioavailability of poorly soluble drugs with pH-dependent solubility.