Co-encapsulation of hydrophilic and hydrophobic drugs into niosomal nanocarrier for enhanced breast cancer therapy: In silico and in vitro studies.

Combination therapy has been considered one of the most promising approaches for improving the therapeutic effects of anticancer drugs. This is the first study that uses two different antioxidants in full-characterized niosomal formulation and thoroughly evaluates their synergistic effects on breast cancer cells. In this study, in-silico studies of hydrophilic and hydrophobic drugs (ascorbic acid: Asc and curcumin: Cur) interactions and release were investigated and validated by a set of in vitro experiments to reveal the significant improvement in breast cancer therapy using a co-delivery approach by niosomal nanocarrier. The niosomal nanoparticles containing surfactants (Span 60 and Tween 60) and cholesterol at 2:1 M ratio were prepared through the film hydration method. A systematic evaluation of nanoniosomes was carried out. The release profile demonstrated two phases (initial burst followed by sustained release) and a pH-dependent release schedule over 72 h. The optimized niosomal preparation displayed superior storage stability for up to 2 months at 4 °C, exhibiting extremely minor changes in pharmaceutical encapsulation efficiency and size. Free dual drugs (Asc + Cur) and dual-drug loaded niosomes (Niosomal (Asc + Cur)) enhanced the apoptotic activity and cytotoxicity and inhibited cell migration which confirmed the synergistic effect of co-encapsulated drugs. Also, significant up-regulation of p53 and Bax genes was observed in cells treated with Asc + Cur and Niosomal (Asc + Cur), while the anti-apoptotic Bcl-2 gene was down-regulated. These results were in correlation with the increase in the enzyme activity of SOD, CAT, and caspase, and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) upon treatment with the mentioned drugs. Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur. Histopathological examination also revealed that Niosomal (Asc + Cur) had a lower mitosis index, invasion, and pleomorphism than Asc + Cur. These findings indicated that niosomal formulation for co-delivery of Asc and Cur would offer a promising delivery system for an effective breast cancer treatment.

Real-World Experience with Cangrelor as Adjuvant to Percutaneous Coronary Intervention: A Single-Centre Observational Study.

Background: Reversible P2Y12 inhibition can be obtained with cangrelor administered intravenously. More experience with cangrelor use in acute PCI with unknown bleeding risk is needed. Objectives: To describe real-world use of cangrelor including patient and procedure characteristics and patient outcomes. Methods: We performed a single-centre, retrospective, and observational study including all patients treated with cangrelor in relation to percutaneous coronary intervention at Aarhus University Hospital during the years 2016, 2017, and 2018. We recorded procedure indication and priority, the indications for cangrelor use, and patient outcomes within the first 48 hours after initiation of cangrelor treatment. Results: We treated 991 patients with cangrelor in the study period. Of these, 869 (87.7%) had an acute procedure priority. Among acute procedures, patients were mainly treated for STEMI (n = 723) and the remaining were treated for cardiac arrest and acute heart failure. Use of oral P2Y12 inhibitors prior to percutaneous coronary intervention was rare. Fatal bleeding events (n = 6) were only observed among patients undergoing acute procedures. Stent thrombosis was observed in two patients receiving acute treatment for STEMI. Thus, cangrelor can be used in relation to PCI under acute circumstances with advantages in terms of clinical management. The benefits and risks, in terms of patient outcomes, should ideally be assessed in randomized trials.

Does vitamin K supplementation improve vitamin K antagonist therapy? A case report and update of the literature.

We report a multi-morbid patient with mechanical aortic valve and unstable and sub-therapeutic levels of international normalized ratio (INR), initially in phenprocoumon and later in warfarin therapy. All efforts, including self-testing using Point of Care Testing with telemedicine support to stabilize the patient's INR within the therapeutic range, were unsuccessful. Since INR fluctuations can occur due to poor or varied dietary vitamin K, 180 µg/day vitamin K was added to the patient's warfarin treatment in an attempt to stabilize INR fluctuations. Three weeks later INR was in therapeutic range and remained within range for two consecutive months suggesting beneficial effect of vitamin K. Our updated literature review demonstrates that vitamin K supplementation can improve the stability of INR without improvement of time therapeutic range. .

Apoptosis Induction, Cell Cycle Arrest and Anti-Cancer Potential of Tamoxifen-Curcumin Loaded Niosomes Against MCF-7 Cancer Cells.

Background & Objective: Breast cancer is the most common cancer among women. One of the most effective treatments for breast cancer is chemotherapy, in which specific drugs destroy the mass and its proliferation is inhibited. Chemotherapy is the most effective adjunctive therapy when multiple medications are used concurrently. Also, combining the drugs with nanocarrier has become an important strategy in targeted therapy. This study is designed to assess the apoptosis induction, cell cycle arrest, and anti-cancer potential of Tamoxifen-Curcumin-loaded niosomes against MCF-7 Cancer Cells. Methods: A novel niosomal formulation of tamoxifen-curcumin with Span 80 and lipid to drug ratio of 20 was employed. The MCF-7 cells were cultured and then treated with IC50 value of tamoxifen-curcumin-loaded niosomes, the combination of tamoxifen and curcumin, tamoxifen, and curcumin alone. Flow cytometry, Real-Time PCR, and cell cycle analysis tests were conducted to evaluate the induction of apoptosis. Results: Drug-loaded niosomes caused up-regulation of bax and p53 genes and down-regulation of bcl2 gene. Flow cytometry studies showed that niosomes containing tamoxifen-curcumin increased apoptosis rate in MCF-7 cells compared to the combination of tamoxifen and curcumin owing to the synergistic effect between the two drugs along with higher cell uptake by formulation niosomal. These results were also confirmed by cell cycle analysis. Conclusion: Co-delivery of curcumin and tamoxifen using optimized niosomal formulation revealed that at acidic pH of MCF-7 cancer cells, released drugs from niosomal carriers would be more effective than physiological pH. This feature of niosomal nanoparticles can reduce the side effects of drugs in normal cells. Niosomal nanoparticles might be used as a biological anti-cancer factor in treatment of breast cancer.

Co-Delivery of Letrozole and Cyclophosphamide via Folic Acid-Decorated Nanoniosomes for Breast Cancer Therapy: Synergic Effect, Augmentation of Cytotoxicity, and Apoptosis Gene Expression.

Breast cancer is one of the most prevalent causes of cancer mortality in women. In order to increase patient prognosis and survival rates, new technologies are urgently required to deliver therapeutics in a more effective and efficient manner. Niosome nanoparticles have been recently employed as therapeutic platforms capable of loading and carrying drugs within their core for both mono and combination therapy. Here, niosome-based nanoscale carriers were investigated as a targeted delivery system for breast cancer therapy. The platform developed consists of niosomes loaded with letrozole and cyclophosphamide (NLC) and surface-functionalized with a folic-acid-targeting moiety (NLCPFA). Drug release from the formulated particles exhibited pH-sensitive properties in which the niosome showed low and high release in physiological and cancerous conditions, respectively. The results revealed a synergic effect in cytotoxicity by co-loading letrozole and cyclophosphamide with an efficacy increment in NLCPFA use in comparison with NLC. The NLCPFA resulted in the greatest drug internalization compared to the non-targeted formulation and the free drug. Additionally, downregulation of cyclin-D, cyclin-E, MMP-2, and MMP-9 and upregulating the expression of caspase-3 and caspase-9 genes were observed more prominently in the nanoformulation (particularly for NLCPFA) compared to the free drug. This exciting data indicated that niosome-based nanocarriers containing letrozole and cyclophosphamide with controlled release could be a promising platform for drug delivery with potential in breast cancer therapy.

Validation of Posturographic Measurements in Adolescents.

OBJECTIVE: The objectives of the present study were to validate the test-retest reliability of static posturography in healthy adolescents aged 13 to 16 years, to identify the most reliable and least variable measurements. PATIENTS: Thirty-two healthy pupils from Skåde Skole participated in this study. INTERVENTION: Static posturography. OUTCOME MEASURES: Subjects were tested for 32 seconds in eight trials (eyes open/eyes closed, on stable ground/foam pads, head neutral/head turned) by using a Tetrax platform. Testing included two rounds of trials and postural regulation was assessed by measuring sway during the eight trials. RESULTS: We found statistically significant lower sway scores during round two in position NO; a similar trend was seen for position NC, PO, HR, HL, and HB, but was not statistically significant. For position PC and HF an increase was seen, but not statistically significant. CONCLUSION: The most reliable and least variable measurements include position NO, NC, PO, and PC. Influence of all three systems involved in maintaining balance is tested in these positions. Static posturography can easily be implemented in a clinical setting as the equipment does not take up much space and is easy to use and instruct the test subjects about. Finally, the costs related to the static posturography are considerably lower compared with dynamic posturography equipment. However, static posturography might not be challenging enough when testing athletic individuals.

Value of sperm chromatin dispersion test in couples with unexplained recurrent abortion.

OBJECTIVE: To evaluate and compare standard sperm parameters and sperm chromatin integrity by sperm chromatin dispersion test (SCD) in ejaculates from men whose partners have a history of recurrent pregnancy loss and from control group of fertile men. METHODS: Thirty couples with unexplained recurrent abortion (case group) and 30 fertile couples (control group) referring to Shiraz infertility center were included. Sperm parameters were assessed in semen samples from two groups and then staining with SCD procedure. The results were analyzed by performing ANOVA and Tukey(,)s tests. RESULTS: In control group, nucleoids with big (65.93 ± 2.35), small (12.4 ± 0.60) and without halo (11.6 ± 0.50) showed significant difference with case group (41.40 ± 1.43), (21.16 ± 1.11) and (23.26 ± 1.10) respectively. In the RPL group spermatozoa with high percentage of abnormal parameters (morphology and motility) was observed (p ≤ 0.05). CONCLUSION: This study strengthens the current literature associating sperm quality with recurrent pregnancy loss, and emphasizes the important of evaluating male factor by tests such as SCD in addition to conventional sperm parameters.

The effects of laser assisted hatching on pregnancy rates.

BACKGROUND: For infertile women aged over 35 years, failure of the ZP (zona pellucida) to rupture is believed to be associated with a decreased implantation rate in in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI). OBJECTIVE: In this research, laser assisted hatching (LAH) was offered to patients with advanced maternal age to evaluate a possible benefit. MATERIALS AND METHODS: Nine hundred thirty two cycles of IVF/ICSI in females were analyzed. Women included in this study were allocated in 4 groups. In group I and II, embryos were cultured and transferred with and without LAH in women aged ≤35, whereas embryos of group III and IV were examined with and without LAH in women aged ≥ 35. Laser manipulations were performed using a suturn-Tm3 system using 2-3 pulses of 0.8 millisecond with 400 voltage duration. The size of the hole made in the zona was measured to be 5-10 µm, depending on the zona thickness of each individual embryo. RESULTS: The performance of LAH significantly increased clinical pregnancy rates in all patients. In group I and II, the chemical (50.99% and 31.61% respectively), clinical (50% and 30.69% respectively) and multiple pregnancies (22.27% and 5.94% respectively) significantly differ between these groups. In the patients with advanced female age ≥35 the performance of LAH significantly increased chemical (30.12%) and clinical pregnancy (27.71%) rates compared to whom without LAH (18.96% and 16.37% respectively). CONCLUSION: Our data demonstrate in the patients who were less than 35 years old, multiple pregnancy rates were significantly increased compared to other groups who aged over 35 years old. In addition benefit of LAH in improving pregnancy rates after IVF or ICSI in women of advanced age (≥35) was shown.