Oil-in-water microemulsion encapsulation of antagonist drugs prevents renal ischemia-reperfusion injury in rats

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received “conventional” SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future

BQIABC: A new Quantum-Inspired Artificial Bee Colony Algorithm for Binary Optimization Problems

Artificial bee colony (ABC) algorithm is a swarm intelligence optimization algorithm inspired by the intelligent behavior of honey bees when searching for food sources. The various versions of the ABC algorithm have been widely used to solve continuous and discrete optimization problems in different fields. In this paper a new binary version of the ABC algorithm inspired by quantum computing, called binary quantum-inspired artificial bee colony algorithm (BQIABC), is proposed. The BQIABC combines the main structure of ABC with the concepts and principles of quantum computing such as, quantum bit, quantum superposition state and rotation Q-gates strategy to make an algorithm with more exploration ability. The proposed algorithm due to its higher exploration ability can provide a robust tool to solve binary optimization problems. To evaluate the effectiveness of the proposed algorithm, several experiments are conducted on the 0/1 knapsack problem, Max-Ones and Royal-Road functions. The results produced by BQIABC are compared with those of ten state-of-the-art binary optimization algorithms. Comparisons show that BQIABC presents the better results than or similar to other algorithms. The proposed algorithm can be regarded as a promising algorithm to solve binary optimization problems

The synthesis of methotrexate-loaded F127 microemulsions and their in vivo toxicity in a rat model

Methotrexate (MTX) has been often formulated as nano and micro-emulsions, nominally to address its poor solubility and off-target effects. Nanoformulated MTX is universally reported to be a more efficacious anti-cancer agent than direct-dissolved drug; however, these investigations generally fail to screen for in vivo toxicity. This study aims to remedy this oversight. MTX was formulated as a standard Pluronic oil-in-water microemulsion with good drug encapsulation efficiency (73.0% ± 8.4). Preliminary in vitro free radical scavenging studies found that formulation reduces drug oxidation four-fold. The toxic effects of formulated and unformulated MTX were investigated in a Wistar rat model. Rats received 0.05 mg/kg MTX as either the microemulsion or directly dissolved in phosphate-buffered saline. A drug-free microemulsion, PBS solution, and saline solution were used as controls. After 28 days, serum levels of enzymes indicative of kidney and liver damage were quantified. Significantly higher serum liver, and serum kidney enzymes were observed in the rats that received the directly dissolved MTX drug (P \u3c 0.05) compared to those who received the encapsulated form. Following sacrifice, the levels of catalase and superoxide dismutase (SOD) were significantly lower and the level of malondialdehyde higher, in rats who received either form of MTX relative to untreated controls. However, the SOD levels were lower in those who received the microemulsion than those who received free MTX. Histology supported the observation that the microemulsion formulation caused no gross structural toxicity to the liver, unlike the free drug. Although toxicity was reduced compared to the free drug, the microemulsion still caused damage to the kidneys. This organ-specific toxicity is consistent with the mode of clearance of the drug. This data demonstrates that the toxicity of formulated drugs must be considered when discussing the relative merits of formulations: encapsulation almost always improves efficacy but may not improve safety

Nanomaterials for the diagnosis and treatment of head and neck cancers: A review

Head and neck cancer (HNC) is a category of cancers that typically arise from the nose-, mouth-, and throat-lining squamous cells. The later stage of HNC diagnosis significantly affects the patient’s survival rate. This makes it mandatory to diagnose this cancer with a suitable biomarker and imaging techniques at the earlier stages of growth. There are limitations to traditional technologies for early detection of HNC. Furthermore, the use of nanocarriers for delivering chemo-, radio-, and phototherapeutic drugs represents a promising approach for improving the outcome of HNC treatments. Several studies with nanostructures focus on the development of a targeted and sustained release of anticancer molecules with reduced side effects. Besides, nanovehicles could allow co-delivering of anticancer drugs for synergistic activity to counteract chemo-or radioresistance. Additionally, a new generation of smart nanomaterials with stimuli-responsive properties have been developed to distinguish between unique tumor conditions and healthy tissue. In this light, the present article reviews the mechanisms used by different nanostructures (metallic and metal oxide nanoparticles, polymeric nanoparticles, quantum dots, liposomes, nanomicelles, etc.) to improve cancer diagnosis and treatment, provides an up-to-date picture of the state of the art in this field, and highlights the major challenges for future improvements

In vitro and in vivo anticancer effect of pH-responsive paclitaxel-loaded niosomes

In this study, paclitaxel (PTX)-loaded pH-responsive niosomes modified with ergosterol were developed. This new formulation was characterized in terms of size, morphology, encapsulation efficiency (EE), and in vitro release at pH 5.2 and 7.4. The in vitro efficacy of free PTX and niosome/PTX was assessed using MCF7, Hela, and HUVEC cell lines. In order to evaluate the in vivo efficacy of niosomal PTX in rats as compared to free PTX, the animals were intraperitoneally administered with 2.5 mg/kg and 5 mg/kg niosomal PTX for two weeks. Results showed that the pH-responsive niosomes had a nanometric size, spherical morphology, 77% EE, and pH-responsive release in pH 5.2 and 7.4. Compared with free PTX, we found markedly lower IC50s when cancer cells were treated for 48 h with niosomal PTX, which also showed high efficacy against human cancers derived from cervix and breast tumors. Moreover, niosomal PTX induced evident morphological changes in these cell lines. In vivo administration of free PTX at the dose of 2.5 mg/kg significantly increased serum biochemical parameters and liver lipid peroxidation in rats compared to the control rats. The situation was different when niosomal PTX was administered to the rats: the 5 mg/kg dosage of niosomal PTX significantly increased serum biochemical parameters, but the group treated with the 2.5 mg/kg dose of niosomal PTX showed fewer toxic effects than the group treated with free PTX at the same dosage. Overall, our results provide proof of concept for encapsulating PTX in niosomal formulation to enhance its therapeutic efficacy. [Figure not available: see fulltext.

Biochemical, ameliorative and cytotoxic effects of newly synthesized curcumin microemulsions: Evidence from in vitro and in vivo studies

Curcumin is known to exhibit antioxidant and tissue-healing properties and has recently attracted the attention of the biomedical community for potential use in advanced therapies. This work reports the formulation and characterization of oil-in-water F127 microemulsions to enhance the bioavailability of curcumin Microemulsions showed a high encapsulation efficiency and prolonged release. To investigate the interactions of curcumin with one unit of the polymeric chain of surfactant F127, ethyl butyrate, and sodium octanoate, as well as the interaction between ethyl butyrate and one unit of the F127 polymer chain, the Density Functional Theory (DFT) calculations at the M06-2X level of theory, were performed in water solution. The MTT assay was used to assess the cytotoxicity of free and encapsulated curcumin on non-malignant and malignant cell lines. Combination effects were calculated according to Chou-Talalay’s principles. Results of in vitro studies indicated that MCF7 and HepG2 cells were more sensitive to curcumin microemulsions. Moreover, a synergistic relationship was observed between curcumin microemulsions and cisplatin in all affected fractions of MCF7 and HepG2 cells (CI < 0.9). For in vivo investigation, thioacetamide-intoxicated rats received thioacetamide (100 mg/kg Sc) followed by curcumin microemulsions (30 mg/kg Ip). Thioacetamideintoxicated rats showed elevated serum liver enzymes, blood urea nitrogen (BUN), and creatinine levels, and a significant reduction in liver superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.05). Curcumin microemulsions reduced liver enzymes and serum creatinine and increased the activity of antioxidant enzymes in thioacetamide-treated rats in comparison to the untreated thioacetamide-intoxicated group. Histopathological investigations confirmed the biochemical findings. Overall, the current results showed the desirable hepatoprotective, nephroprotective, and anti-cancer effects of curcumin microemulsions

F127/cisplatin microemulsions: In vitro, in vivo and computational studies

The development of effective strategies for local administration of chemotherapeutic drugs, thus minimizing the adverse side effects to patients, is one of the key challenges in biomedicine and cancer research. This work reports the formulation and characterization of PluronicF127 microemulsions to enhance the bioavailability of Cisplatin (Cis). The size of Cis microemulsion was about 12.0 nm, as assessed by dynamic light scattering analysis. In vitro cytotoxic activity of free Cis and F127/Cis microemulsions were studied on malignant (C152 and MCF7) and normal (HUVEC) cells via tetrazolium (MTT) colorimetric assay. Cell morphology was also monitored. In vitro assessments revealed thatF127/Cis microemulsions induced cytotoxicity/morphological changes to a lesser extent than free Cis. Regarding in vivo experiments, F127/Cis microemulsions were injected intraperitoneally at 7 and 14 mg/kg doses into adult male Wistar rats to assess histologic and biochemical changes. In this case, the bulk Cis group caused severe histopathological changes and significant increases in serum liver enzymes and serum kidney function markers. The group treated with the 14 mg/kg dose of F127/Cis microemulsions also showed severe fatty changes and significant increases in serum liver enzymes, blood urea nitrogen, and creatinine levels. The group treated with the low dose of nano-Cis showed a significant increase in serum liver enzymes levels accompanied by mild fatty changes of the liver. Theoretical surveys were performed to get an understanding of the interplay between F127 and Cis. Results reveal that hydrogen bonding (HB) interactions with F127have an influence on the molecular properties of Cis and may playa role in the lower toxicity of F127/Cis in comparison to free Cis

Psychometrics properties of the Iranian version of fertility quality of life tool: a cross- sectional study

Background: Clinical measurement of quality of life for assessing reproductive problems should be considered as a standard investigation at the initial and continuing medical consultations with infertile people. Objective: The purpose of this study was comprehensive testing the psychometric properties of the Iranian version of fertility quality of life (FertiQol) as its use could be considerable due to the prevalence of infertility in Iran and the importance of evaluation of QoL in patients with infertility. Method and material: This was a psychometric properties study of 300 women referred to infertility clinic, Hormozgan, Iran. After linguistic validation of the Iranian version of MPCOSQ, a semi-structured interview was conducted to assess face validity. Consequently exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to indicate the scale constructs. Discriminant validity was assessed using the known groups comparison. Convergent validity was evaluated by assessing the correlation between similar content on the 12-Item Short Form Health Survey, Hospital Anxiety and Depression Scale and FertiQol. In addition, reliability analysis was carried out with internal consistency. Results: The reliability of the Iranian version of the FertiQol questionnaire was satisfactory in all dimensions (Cronbach’s alpha ranging from 0.77 to 0.83 ). Six factors (emotional, mind/body, relational, social, environmental and tolerability) were extracted from the results of EFA with factor loading of the more than 0.3. Discrimination validity showed that FertiQol can differentiate between female patients with differing duration of infertility and number of children; this indicates favorable discrimination validity. Moreover, the results of convergent validity showed a favorable correlation between the related dimensions of 12-Item Short Form Health Survey (correlation ranging from 0.43 to 0.68 ), Hospital Anxiety and Depression Scale(correlation ranging from 0.47 to 0.52 ) and FertiQol. Conclusion: The Iranian version of FertiQol is valid and reliable for assessing infertility problems and the effects of treatment on quality of life of infertile patients referred for diagnosis and treatment at an Iranian infertility clinic. The clinical use of this measure is recommended for Iranian infertility clinics

CoNi alloy nanoparticles for cancer theranostics: synthesis, physical characterization, in vitro and in vivo studies

Nanomaterials are attracting increasing interest in many biomedical fields, including the fight against cancer. In this context, we successfully synthesized CoNi alloy nanoparticles (NPs) by a simple polyol process. The magnetic characteristics of the products were measured by vibration sample magnometry, which revealed that the samples have soft ferromagnetic behavior. The microstructure and morphology were inspected by X-ray diffraction and scanning electron microscopy, respectively. Human cancer cells derived from the breast (MCF7) and oral cavity (C152) and normal cells derived from human umbilical vein endothelial cells (HUVECs) were treated with increasing concentrations of CoNi NPs, and their cytotoxic effect was measured via MTT and lactate dehydrogenase (LDH) leakage assays. We found that treatments by using 12.5 to 400 µg/mL of Co0.5Ni0.5, Co0.6Ni0.4, and Co0.4Ni0.6 NPs were associated with significant concentration-dependent toxicity toward such cell lines and profoundly enhanced LDH leakage following 48 h of exposure (P < 0.05 compared with untreated cells). Besides, a NP dose of 6.25 µg/mL did not affect the survival of HUVECs while leading to marked cell death in MCF7 and C152 cells. In vivo experiments in rats were done to investigate the biochemical and histopathological changes over three weeks, following intraperitoneal administration of Co0.5Ni0.5, Co0.6Ni0.4, and Co0.4Ni0.6 NPs (100 mg/kg). As compared with the controls, the exposure to NPs caused significant elevations in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, serum creatinine, serum catalase activity, serum superoxide dismutase, and liver malondialdehyde levels. Also, rats treated with Co0.6Ni0.4 NPs showed more severe histopathological changes of the liver and kidney. Our findings represent an essential step toward developing theranostic nanoplatforms for selective cancer treatment