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We would love to hear of your unique problem, you may be surprised as chances are, your solution is already built. We never share or sell information, so inquire with confidence today. NCSS established Like most advancements in technology, NCSS was founded out of necessity. Our founding members had a need for NC software which could not only accommodate for mis-aligned material in their machines via offsets, but have the ability to work with irregular and mis-shaped parts, make adjustments on the fly, and produce a good part the first time through.
It was a very tall order Fortunately, this team of engineers with over 20 years of aero-space manufacturing experience had the skill and patience to develop the first version of our NC Transform NCT product. NCT has become an invaluable component of the production process for manufacturers all over the world as it achieves the end result we are all looking for: Make a good part the first time or don't run at all.
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See what you've been missing Machine monitoring for Industry 4. Maximize the value of each part in the process Learn more. Adaptive Machining Eliminate re-work and human error in your NC process. Machine Monitoring Our Machine Communication System allows one to monitor all machine activity in the shop and easily manage the data and improved efficiency. Five Axis Tool Compensation Use reground tools even in the most complex of geometries, providing tool cost savings.
Tool Management Get the most out of your tooling without risking over-utilization. Request Info. NC Transform Adaptive machining software for the modern factory.
Eliminate Human Error Let's face it, human error in manufacturing can be a problem. Best Fit Technology Irregular part? Eliminate Re-work Yes, we said eliminate re-work. User Friendly After NCT is setup in your shop, it usually only takes a short training session for the NC programmers and the operators to become a fully integrated part of your process.
Learn More. The efficacy of systemic chemotherapy for hepatocellular carcinoma HCC is predominantly hampered by low accumulation in tumor tissue and the high systemic toxicity of anticancer drugs. In this study, we designed an in situ drug-loaded injectable thermosensitive hydrogel system for the simultaneous delivery of norcantharidin-loaded nanoparticles NCTD-NPs and doxorubicin Dox via intratumoral administration to HCC tumors.
The rheological properties of the drug-loaded hydrogel were studied using a rheometer. Drug release of the drug-loaded hydrogel and cytotoxicity in HepG2 cells were evaluated in vitro. An H22 tumor-bearing mice model was used to assess the in vivo antitumor activity of the drug-loaded hydrogel via intratumoral administration. The prepared drug-loaded hydrogel exhibited good thermal-sensitive properties, which remained liquid at room temperature and rapidly transformed into a non-flowing gel at body temperature, and released the drugs in a sustained manner.
In vitro studies revealed that the drug-loaded hydrogel exhibited remarkable antiproliferative activity in HepG2 cells compared to free drugs. In vivo antitumor efficacy experiments showed that the drug-loaded hydrogel significantly suppressed tumor growth, alleviated side effects, and prolonged the survival time of mice bearing H22 tumors compared to the other groups.
The formulated hybrid thermosensitive hydrogel system with sustained drug release and enhanced therapeutic efficacy was demonstrated to be a promising strategy for the local-regional treatment of HCC via intratumoral administration. Globally, hepatocellular carcinoma HCC ranks the sixth most frequently diagnosed malignancy and the fourth leading cause of cancer-associated mortality. However, the systemic intravenous administration of chemotherapeutic agents manifests severe adverse effects due to non-selective drug biodistribution in healthy tissues and organs.
Besides, the relatively low bio-accessibility of these drugs to target tumor tissues and the rapid clearance from blood circulation can lead to inadequate therapy, which seriously affects therapeutic efficacy and leads to an increased incidence of drug resistance.
Doxorubicin Dox , a representative anthracycline antibiotic and effective anticancer drug with broad-spectrum activity functions by inducing DNA damage in cancer cells through multiple mechanisms, including intercalation into DNA and the inhibition of topoisomerase II.
Besides, the rapid metabolism of Dox to inactive derivatives mainly via the liver after intravenous injection is also a critical issue that remains unresolved.
However, NCTD has poor water solubility, short half-life after oral or intravenous administration, and low tumor-targeting efficiency, significantly affecting its anticancer effect. Recently, polymeric nanoparticles have gained increasing attention owing to their potential to deliver drugs efficiently.
By virtue of nanoparticle formulations, the coupling of antitumor drugs with polymeric drug carriers can improve the pharmacological properties of drugs, particularly the water solubility of hydrophobic pharmaceuticals. Anticancer agents can also efficiently accumulate in tumor tissues through the enhanced permeability and retention EPR effect, thereby enhancing the therapeutic efficacy and reducing adverse effects.
Previously, PCEC nanoparticles were successfully prepared to deliver anticancer drugs, such as gefitinib, paclitaxel, and honokiol, and appeared to be a sustained drug release system.
Injectable in-situ-forming hydrogels have received considerable attention due to their outstanding properties, such as excellent biocompatibility, facile preparation, minimal invasiveness, shape adaptability, and improved patient compliance, making them excellent candidates for biomedical applications. In this study, an in situ dual drug-loaded hydrogel system was constructed to simultaneously deliver NCTD-NPs and Dox via intratumoral administration for sustained and efficient antitumor therapy.
The composite hydrogel system was prepared and optimized, and the physicochemical properties were characterized. HepG2 cells and H22 tumor-bearing mice model were used to evaluate in vitro and in vivo antitumor activity of the PF drug-loaded hydrogel via intratumoral administration.
Dalian, China. Ltd Tianjin, China. All reagents were analytical grade and used as received without further purification. The animals were provided access to standard laboratory chow and tap water ad libitum. All mice were healthy and had no infection during the experimental period.
After cooling to room temperature under a nitrogen atmosphere, the synthesized copolymer was dissolved in dichloromethane and reprecipitated from the filtrate with an excess of cold petroleum ether. Finally, the PCEC copolymers were vacuum dried to a constant weight and stored in a desiccator until use.
Similarly, blank nanoparticles were prepared using the above technique without the addition of NCTD. The flow rate was 0. DL and EE were calculated using the following equations:. Then, 85 mg of NCTD-NPs and 30 mg of doxorubicin were added to the clear solution prepared above and gently mixed with a magnetic stirrer to form a uniform mixture.
The blank hydrogel was fabricated using a similar procedure by adding only an appropriate amount of blank nanoparticles. The temperature sweep test was performed at a fixed frequency of 1 Hz and a gap size of 0. The in vitro release behavior of the drug from the nanoparticles and hydrogel was assessed using the dialysis membrane method. At the scheduled time, 2 mL of the release medium was removed and replaced with an equivalent volume of prewarmed fresh medium.
After centrifugation at 12, rpm for 15 min, 1 mL of supernatant was taken for further analysis. All measurements were performed in triplicate. Finally, the absorbance was measured at nm using a microplate reader Omega, Germany. When the volume of the solid tumors reached — mm 3 , the tumor-bearing mice were randomly divided into four groups of ten mice each: 1 normal saline NS , 2 blank hydrogel, 3 free NCTD 2.
The time was defined as day 0. Subsequently, the mice were injected intratumorally with 0. The tumor volume and body weight were measured on alternative days from the start of treatment. Body weight changes of the mice were observed to assess the toxicity of the treatments. Half of the mice in each group were selected at random and sacrificed by cervical dislocation on day The tumors and major organs heart, liver, spleen, lung, and kidney were immediately excised.
Eventually, the remaining mice five mice in each group were used for survival analysis. Statistical analysis was performed using GraphPad Prism version 6. The Kaplan-Meier method was used to plot the survival curve and compared using the log-rank test. After incubation with blank NPs, free coumarin-6, and coumarinloaded nanoparticles for 2 h, images were obtained using a fluorescence microscope as presented in Figure 1D.
The control a and blank nanoparticles b groups appeared completely black with no fluorescence. However, the other two groups showed significant fluorescence, and coumarinloaded nanoparticles d exhibited a higher density of fluorescence than free coumarin-6 c , suggesting that coumarinloaded nanoparticles were taken up efficiently by the HepG2 cells.
Rheological properties were investigated using a rheometer. The in vitro release behavior of the free NCTD and NCTD-NPs was investigated by the dialysis membrane method to assess the feasibility of the sustained release of the encapsulated drugs. These results indicated that the NPs allowed sustained drug release. Furthermore, the in vitro release behavior of NCTD and Dox from the drug-loaded hydrogel was also investigated.
Taken together, these results implied that the drug-loaded hydrogel exhibited a sustained and extended-release behavior for the encapsulated drugs. This indicated that PCEC nanoparticles could be considered as a safe carrier for drug delivery systems. Consistently, the IC50 value of Dox was lower in drug-loaded hydrogel 0.
During the experimental periods, the body weight of the mice was monitored regularly, and the results are presented in Figure 4C. Histological analysis of the major organs showed no visible tissue damage, inflammation, or lesions Figure 5. At the end of the experiment, the mice were sacrificed, and the tumors were collected for further histological and immunohistochemical analysis. As shown in Figure 6 , the tumors treated with free drugs exhibited a lower proportion of necrotic cells than those treated with drug-loaded hydrogel, whereas the saline- and blank hydrogel-treated tumors exhibited no significant necrosis.
As presented in Figure 7A , Ki and CD31 immunostaining were investigated to assess tumor cell proliferation and tumor angiogenesis. These findings indicated that the drug-loaded hydrogel more effectively inhibited tumor proliferation and angiogenesis, suggesting that drug-loaded hydrogel could exert enhanced antineoplastic activity.
B The quantitative analysis of Ki expression in each group. C The quantitative analysis of vascularization in each group.
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