Application of nanoparticles in breast cancer treatment: a systematic review.

It is estimated that cancer is the second leading cause of death worldwide. The primary or secondary cause of cancer-related mortality for women is breast cancer. The main treatment method for different types of cancer is chemotherapy with drugs. Because of less water solubility of chemotherapy drugs or their inability to pass through membranes, their body absorbs them inadequately, which lowers the treatment's effectiveness. Drug specificity and pharmacokinetics can be changed by nanotechnology using nanoparticles. Instead, targeted drug delivery allows medications to be delivered to the targeted sites. In this review, we focused on nanoparticles as carriers in targeted drug delivery, their characteristics, structure, and the previous studies related to breast cancer. It was shown that nanoparticles could reduce the negative effects of chemotherapy drugs while increasing their effectiveness. Lipid-based nanocarriers demonstrated notable results in this instance, and some products that are undergoing various stages of clinical trials are among the examples. Nanoparticles based on metal or polymers demonstrated a comparable level of efficacy. With the number of cancer cases rising globally, many researchers are now looking into novel treatment approaches, particularly the use of nanotechnology and nanoparticles in the treatment of cancer. In order to help clinicians, this article aimed to gather more information about various areas of nanoparticle application in breast cancer therapy, such as modifying their synthesis and physicochemical characterization. It also sought to gain a deeper understanding of the mechanisms underlying the interactions between nanoparticles and biologically normal or infected tissues.

The effect of multi-function swing suspension training on upper and lower extremities function and quality of life in multiple sclerosis women with different disability status.

BACKGROUND: Multiple sclerosis (MS) can lead to impaired upper and lower extremity function (ULEF), which reduces the quality of life (QoL). Exercise is beneficial for symptom management, but newer approaches like multi-function swing suspension training (MFSST) need further investigation. Additionally, tailoring exercises to individual needs remains a challenging area of investigation. AIM: To investigate the effect of an MFSST program on ULEF, and QoL in MS women according to the expanded disability status scale (EDSS) score. METHODS: Forty-seven MS women meeting selection criteria were randomly assigned to intervention groups A (EDSS 2-4) and B (EDSS 4.5-6.5), and the control group (EDSS 2-6.5). Intervention groups did an 8-week MFSST program with 3 × 1hr sessions/week. Prior to the intervention, and after 4, 6, and 8 weeks, the 9-hole peg test (9HPT) and the timed 25-foot walk (T25FW) test were performed for both the intervention groups and the control group. The Short Form questionnaire (SF-36) was used to measure their QoL. RESULTS: Significant main effects for time were observed in both the 9HPT (F = 52.48, p = 0.001, Pη2 = 0.78) and the T25FW (F = 85.63, p = 0.000, Pη2 = 0.859). Speed increased between the pre-test, 4th week, 6th week, and 8th week in both tests. These tests revealed significant interaction effects between group and time. The 9HPT had an F-value of 9.01 (p = 0.001, Pη2 = 0.392), while the T25FW had an F-value of 13.812 (p = 0.000, Pη2 = 0.497). Across both tests, Group B, with higher EDSS scores, demonstrated greater speed improvement over the three-time measurements (4th week, 6th week, and 8th week) than Group A. The control group did not exhibit any improvement in speed. Intervention groups showed improvement in all QoL subscales except emotional role limitation. CONCLUSIONS: An 8-week MFSST improves ULEF and QoL in women with MS, particularly those with higher EDSS scores (more than 4.5). Notably, significant improvements were observed after four weeks of the intervention. The incorporation of a variety of exercises in a single device provides a significant advantage over traditional exercise programs. Therefore, MFSST can be a valuable and efficient tool for improving symptoms and QoL in MS patients. TRIAL REGISTRATION: IRCT20220526054997N1.

Radiotherapy Improves the Disability in Patients with Secondary Progressive Multiple Sclerosis.

Background: Multiple sclerosis (MS) as a complex neurological abnormality is marked with loss of myelin and axons due to chronic inflammatory and autoimmune responses. The modulatory properties of the low dose radiation (LDR) on inflammatory and immune responses have well known. Objective: The current research aimed to assess the impacts of LDR on the disability in patients suffering from MS. Material and Methods: This experimental pilot study was done on 10 patients with secondary progressive multiple sclerosis (SPMS). After magnetic resonance imaging, the SPMS patients were treated by LDR at a daily dose of 2 Gray for 5 consecutive days (totally 10 Gray dose) using a linear accelerator. The extent of the disability was evaluated one week after the completion of radiotherapy using expanded disability status scale (EDSS). Results: After receiving radiotherapy, the patients had a feeling of wellbeing of some sort. The mean of EDSS was significantly reduced after radiotherapy compared with before irradiation (7.4±0.45 vs 6.35±1.18; P<0.017). EDSS more decreased in younger SPMS patients (P=0.0001), and in the women after LDR (P=0.027). Conclusion: Radiotherapy can reduce fatigue and EDSS in patients with SPMS. The age and gender of patients may influence the LDR efficacy.

A self-healable and bioadhesive acacia gum polysaccharide-based injectable hydrogel for wound healing acceleration.

The present study aimed at developing an injectable hydrogel based on acacia gum (AG) for wound healing acceleration. The hydrogels were synthetized through metal-ligand coordination mediated by Fe3+ and characterized in terms of gelation time, gel content, initial water content, swelling capacity, water retention ratio, and porosity. Moreover, FTIR, XRD and TGA analyses were performed for the hydrogels and allantoin (Alla) loaded ones. Furthermore, bioadhessiveness, and self-healing as well as antibacterial, toxicity and wound healing potentials of the hydrogels were evaluated. The hydrogels displayed fast gelation time, high swelling, porosity, and bioadhessiveness, as well as antioxidant, self-healing, antibacterial, blood clotting, and injectability properties. FTIR, XRD and TGA analyses confirmed hydrogel synthesis and drug loading. The Alla-loaded hydrogels accelerated wound healing by decreasing the inflammation and increasing the cell proliferation as well as collagen deposition. Hemocompatibility, cell cytotoxicity, and in vivo toxicity experiments were indicative of a high biocompatibility level for the hydrogels. Given the advantages of fast gelation, injectability and beneficial biological properties, the use of Alla-loaded hydrogels could be considered a new remedy for efficient wound healing.

Curcumin-Loaded Chitosan Nanoparticle Preparation and Its Protective Effect on Celecoxib-induced Toxicity in Rat isolated Cardiomyocytes and Mitochondria.

Curcumin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory and tissue protective. In here we hypothesized that curcumin-loaded chitosan-coated solid lipid nanoparticles (CuCsSLN) are able to increase its overall bioavailability and hence its antioxidant and mitochondria;/lysosomal protective properties of curcumin. CuCsSLN were prepared using solvent diffusion technique for formation of solid lipid nanoparticles (SLNs) and electrostatic coating of positive-charged chitosan to negative surface of SLNs. CuCsSLN showed the encapsulation efficiency of 91.4±2.7%, the mean particle size of 208±9 nm, the polydispersity index of 0.34±0.07, and the zeta potential of+53.5±3.7 mV. The scanning electron microscope (SEM) images of nanoparticles verified their nanometric size and also spherical shape. Curcumin was released from CuCsSLN in a sustain release pattern up to 24 hours. Then isolated cardiomyocytes and mitochondria were simultaneously treated with (1) control (0.05% ethanol), (2) celecoxib (20 µg/ml) treatment, (3) celecoxib (20 µg/ml)+++CuCsSLN (1 µg/ml) treatment, (4) CuCsSLN (1 µg/ml) treatment, (5) celecoxib (20 µg/ml)+++curcumin (10 µM) treatment and (6) curcumin (10 µM) treatment for 4 h at 37°C. The results showed that celecoxib (20 µg/ml) induced a significant increase in cytotoxicity, reactive oxygen species (ROS) formation, mitochondria membrane potential (ΔΨm) collapse, lipid peroxidation, oxidative stress and mitochondrial swelling while CuCsSLN and curcumin reverted the above toxic effect of celecoxib. Our data indicated that the effect of CuCsSLN in a number of experiments, is significantly better than that of curcumin which shows the role of chitosan nanoparticles in increasing effect of curcumin.

Evaluation of Date Extract on Nerve Conduction Velocity in Male Rats.

Introduction: Neuropathy is a condition in which the Peripheral Nervous System (PNS) is disordered. Studying the effects of antioxidants on the performance improvement of this system is vital. This study aimed to investigate the effects of date extract on Nerve Conduction Velocity (NCV), Distal Motor Latency (DML), and wave height of the sciatic nerve in male rats. Methods: This laboratory study used 24 male Wistar rats weighing 250-300 g, divided into the test and control groups. The test group received 10% date extract daily, at 4 mL/kg of body weight, for three weeks. In the beginning, nerve Conduction Velocity (NCV), Distal Motor Latency (DML), and wave height of the sciatic nerve were examined in all animals and reexamined for NCV three weeks later. P-values lower than 0.05 were considered significant. Results: Sciatic NCV and wave height were significantly increased; however, compared to the control group, DML of the knee significantly declined in the test group. Conclusion: The compositions of date extract accelerate electrical signal transmission. Highlights: Irreparable damages to the Peripheral Nervous System (PNS) are major problems in societies.Different therapeutic methods have been adopted for peripheral nerve repair.According to FAO, the production and use of dates are rising.Dates are used in traditional medicine for curing hoarseness, paralysis, backache, and rheumatic pains. Plain Language Summary: Dates are highly important in our nutrition. There have been studies on the positive antioxidative effects of date extract in preventing diabetic neuropathy. Dates are used in traditional medicine for curing hoarseness, paralysis, backache, and rheumatic pains, among others. The importance of dates is derived from their rich compositions of carbohydrates, salts and minerals, dietary fiber, vitamins, fatty acids, amino acids, and proteins. Different therapeutic methods have been adopted for PNS, still, 50% of these damages become permanent and cause disability. Date palms are in the palm family native to Iran, and found in relatively tropical regions.Dates are used in traditional medicine for curing hoarseness, paralysis, backache, and rheumatic pains, among others. In short, the compositions of date extract accelerate electrical signal transmission.

Improvement in the multiple sclerosis functional composite score by multi-function swing suspension training program.

BACKGROUND: Physical activity has been considered as a promising approach to slow down the disease process in Multiple Sclerosis (MS) patients. The functional impairments of MS have been studied in detail, while evidence of the efficacy of exercise training interventions on the Multiple Sclerosis functional composite (MSFC) score in these patients is limited. The aim of this study was to investigate the improvement in MSFC score by multi-function swing suspension training program (MFSST) in the women with MS. METHODS: The patients were divided into two groups as the intervention and control groups. A total of 47 MS patients completed the MSFC components at baseline and after the intervention: the timed 25-foot walk (T25FW); the 9-hole peg test (9HPT); and paced auditory serial addition test (PASAT). Z scores were created for each test based on control means. RESULTS: The MSFC score, 9HPT, T25FW, and PASAT showed a significant increment in comparison with the baseline levels in the four, six, and eight weeks following the first exercise session (all p<0.05). These differences in the control group were not significant. The improvement in the MSFC score and the component Z-scores in the intervention groups was found from the fourth week onwards. CONCLUSIONS: The study findings highlight that the progression of MS disability can be partially compensated by physical exercise. Overall, these results indicate that MFSST can be used as an effective treatment method in patients suffering from MS. Longer (years) exercise studies with larger samples of MS patients, with different MS subtypes, and of different sex, are needed to evaluate the effect of other types of exercise interventions on the MSFC score in MS patients with different disabilities.

Crocin attenuates inflammation of lung tissue in ovalbumin-sensitized mice by altering the expression of endoplasmic reticulum stress markers.

Endoplasmic reticulum (ER) stress plays a pivotal role in the pathogenesis of asthma. The present study aimed to investigate the reducing or suppressing effects of crocin in ovalbumin (OVA)-sensitized mice on ER stress markers. Mice were divided into six groups (n = 5 per group) including control, OVA-sensitized (OVA), OVA-treated crocin (OVA-Cr25, OVA-Cr50, and OVA-Cr100 mg/kg), and OVA-treated dexamethasone (1 mg/kg), (OVA-Dexa) groups. Animals 5 later groups were sensitized to OVA and the treatment groups received intraperitoneally crocin/dexamethasone in the last 5 days of the model. At the end of the study, lung tissue was evaluated for airway inflammation, caspase 12 and CHOP protein levels, and expression of ER stress markers using real-time-PCR. Sensitization with OVA significantly caused airway inflammation and induction of ER stress in mice compared to the control group based on the elevated inflammatory cells and ER stress markers in the lung tissue. Treatment with crocin and dexamethasone reduced airway inflammation and suppressed ER stress markers. Interestingly, in the OVA-Cr100 group, the suppressive effects on ER stress apoptotic markers were comparable to the OVA-Dexa group. The results suggest that crocin mediates maladaptive ER stress conditions possibly by creating adaptive ER stress status and driving protein folding correctly.

Design and Invitro Characterization of Green Synthesized Magnetic Nanoparticles Conjugated with Multitargeted Poly Lactic Acid Copolymers for Co-delivery of siRNA and Paclitaxel.

BACKGROUND: The self-assembling of various amphipathic copolymers is a simple method that allows the preparation of complex nanoparticles with several useful properties. In the present study, the polylactic acid-polyethylene glycol-folate (PLA-PEG-FA) (PPF), PLA-PEG-T7 peptide (PPT) and PLA-Chitosan-Spermine (PCS) copolymers were synthesized separately. METHODS: These copolymers combined with Fe3O4 magnetic core and loaded with paclitaxel (PTX)/siRNA-FAM to form magnetic PCS/PPF/PPT/PTX/siRNA micelles (MPCSFT/PTX/siRNA) and were characterized using physicochemical and biological analysis. RESULTS: The results revealed that the MPCSPFT/PTX/siRNA had spherical morphology with particle size and zeta potential about 197 nm and -7.8 mV, respectively. Release assay was determined under neutral (pH=7.4) and acidic pH (pH=6) conditions to simulate PTX and siRNA release profile from MPCSPFT/PTX/siRNA micelles in normal and cancerous tissues. The ability of MPCSPFT for co-delivery of PTX and siRNA into MCF-7 cells was determined by MTT and flow cytometry tests, respectively. The results revealed that the release rate of siRNA and PTX from MPCSPFT/PTX/siRNA nanoparticles under an acidic environment (pH=6) was significantly higher than that of their release rate in a neutral medium (pH=7.4). CONCLUSION: Conjugation of both folic acid and T7-peptide on the surface of micelles compared to separate conjugation of one of these ligands, increased the efficiency of drug and siRNA delivery to breast cancer cells.

Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel.

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel (PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid (FA) and glucose (Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCo-polyethyleneimine (FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol (PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu (NPsB) and FeCo-PEI-PLA-PEG-FA/Glu (NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX. Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

Height, shape and anterior-posterior diameter of pituitary gland on magnetic resonance imaging among patients with multiple sclerosis compared to normal individuals.

Background: Several studies indicate contribution of hypothalamus-pituitary-adrenal (HPA) axis in multiple sclerosis (MS) disease. This study was designed to determine whether there is an effective difference in pituitary height, shape, and anterior-posterior diameter (APD) between patients with MS and the control group. Methods: In this study, sagittal pituitary height and APD of 134 men and women (64 patients with MS and 70 healthy subjects as control group) were measured by T1 sequence magnetic resonance imaging (MRI). All the subjects were free of sellar or parasellar pathology without a history of surgical intervention or prolactin affecting drugs like bromocriptine and cabergoline or corticosteroid consumption. Results: Mean height of pituitary gland was 6.62 ± 1.43 and 5.78 ± 1.15 mm for patients and the control group, respectively, and the difference between the two groups was statistically significant (P = 0.001). Mean APD was 10.40 ± 1.29 mm for the group of patients and 10.25 ± 1.41 mm for the control group, respectively, without significant differences. 46.9%, 37.5%, and 15.6% of patients had flat, convex, and concave hypophyseal surfaces, respectively. This rate was 50%, 30%, and 20% among the control group, respectively. There was no significant difference between our measurements among patients on whom imaging study was performed at time of disease onset with others. Conclusion: Mean height of pituitary gland among patients with MS was significantly greater than the control group (P = 0.001). So can we consider the same etiology for pituitary hypertrophy among patients with MS as a hypothesis?

Development and characterization of a novel lipohydrogel nanocarrier: repaglinide as a lipophilic model drug.

OBJECTIVES: Solid lipid nanoparticles (SLNs) are highly susceptible to phagocytosis by reticuloendothelial system (RES). To overcome this problem, a novel hydrogel-coated SLNs structure was developed and evaluated in this study. METHODS: Solid lipid nanoparticles surface was coated with chitosan, via electrostatic attraction with the negatively charged SLNs surface. The resulting polymer-coated SLNs then hosted an inorganic poly-anionic agent, tripolyphosphate, to form the final lipohydrogel structure. KEY FINDINGS: Compared with the bare SLNs, lipohydrogel nanoparticles (LHNs) showed a significant increase in size and zeta potential. The release profile showed lower burst release and lower release rate for LHNs compared with SLNs. LHNs nanoparticles released the model antidiabetic drug, repaglinide, in a more sustained manner with lower burst effect compared with the corresponding SLN structure. Cytotoxicity studies via cell culture and MTT assay revealed no bio-toxicity of the SLNs and LHNs. In addition, intravenous administration of repaglinide-loaded SLNs and LHNs in rats showed longer drug residence time in circulation for LHNs, a trend also evident for the blood glucose level-time profile. CONCLUSION: The particle size, zeta potential, FTIR and microscopy data demonstrated the formation of the supposed lipohydrogel nanoparticles. All these benefits of LHNs propose it as a promising candidate for controlled release of the drugs.

Study of the involved vascular territories in patients with ischemic stroke in Kerman, Iran.

BACKGROUND: The races show different cerebrovascular involvements, for example, the involvement of intracranial arteries are higher among Asians than Caucasians. The aim of this study was to investigate the cerebrovascular stenosis pattern by computed tomography angiography (CTA), which is unprecedented in Iran. METHODS: In this study, patients with brain stroke (thrombosis), confirmed by CT scanning and cardiac assessments, who referred to Shafa Hospital in Kerman, Iran, underwent brain and cervical arteries CT angiography to assess involved cerebrovascular territories and also its risk factors from June 2012 to June 2013. RESULTS: We did CTA for 100 patients. Eighty-four cases had cerebral artery stenosis. Intracranial vessel involvement alone was observed in 47.6% of patients, simultaneous intracranial and extracranial artery stenosis in 26.2%, and extracranial artery stenosis in 26.2%. Posterior cerebral artery territory showed the highest degree of vascular stenosis. Posterior cerebral artery stenosis alone was observed in 51.3% of the cases; 27.4% of the cases suffered from anterior artery stenosis, and 21.6% had simultaneous anterior and posterior cerebral artery stenosis. Smokers showed higher extracranial artery involvement compared to non-smokers; 44% of smokers and 14% of non-smokers had extracranial vertebral involvement. CONCLUSION: Our findings showed that intracranial artery involvement was the most prevalent finding in patients with thrombotic stroke in Kerman. Also posterior cerebral artery stenosis was more prevalent than anterior artery stenosis. Hypertension was the most common risk factor. Furthermore, smoking was considered as an important risk factor for extracranial artery stenosis, especially in the posterior cerebral artery.

Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles.

BACKGROUND: Repaglinide is an efficient anti-diabetic drug which is prescribed widely as multi-dosage oral daily regimens. Due to the low compliance inherent to each multi-dosage regimen, development of prolonged-release formulations could enhance the overall drug efficacy in patient populations. METHODS: Repaglinide-loaded solid lipid nanoparticles (SLNs) were developed and characterized in vitro. Various surfactants were used in this study during the nanocarrier preparation procedure and their corresponding effects on some physicochemical properties of SLNs such as size, zeta potential; drug loading parameters and drug release profiles was investigated. Stearic acid and glyceryl mono stearate (GMS) were used as lipid phase and phosphatidylcholin, Tween80, Pluronic F127, poly vinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) were used as surfactant/stabilizer. RESULTS: The results showed some variations between formulations; where the Tween80-based SLNs showed smallest size, the phosphatidylcholin-based SLNs indicated most prolonged drug release time and the highest loading capacity. SEM images of these formulations showed morphological variations and also confirmed the nanoscale size of these particles. The FTIR and DSC results demonstrated no interaction between drug and excipients. The invitro release profiles of different formulations were studied and observed slow release of drug from all formulations. However significant differences were found among them in terms of their initial burst release as well as the whole drug release profile. From fitting these data to various statistical models, the Peppas model was proposed as the best model to describe the statistical indices and, therefore, mechanism of drug release. CONCLUSION: The results of this study confirmed the effect of surfactant type on SLNs physicochemical properties such as morphological features, loading parameters, particle sizes and drug release kinetic. With respect to the outcome data, the mixture of phosphatidylcholin/Pluronic F127 was selected as the best surfactant/stabilizer to coat the lipid core comprising stearic acid and GMS.

Evaluation of the Effects of Charged Amino Acids on Uncontrolled Seizures.

Introduction. Epilepsy is one of the most common diseases of the central nervous system. The prevalence of epilepsy throughout the world is 0.5 to 1%, and the same rate is 7.8 per 1000 in Kerman. Almost 20 to 30% of epileptic patients do not respond properly to common medications. The present study investigated patients who did not respond to common and, even in some cases, adjuvant therapies, with two seizures or more per week, regardless of the type of the inflicted epilepsy. Methodology. The participants of the present double-blind study were randomly selected into three 10-member groups of uncontrolled epileptic patients (arginine, glutamic acid, and lysine). The patients used amino acid powder dissolved in water (three times the daily need) every day for two weeks before breakfast. The number of seizures was recorded one week prior to commencing amino acid use, as well as the first and the second weeks subsequent to use. Results. A total of 32 patients were studied in three groups. The decline rates of seizures were 53%, 41%, and 13%, and the P value was 0.013, 0.027, and 0.720, respectively. Conclusion. Administration of the charged amino acids, arginine, and glutamic acid can decrease the seizures of patients suffering from uncontrolled epilepsy.

Comparison of serum levels of copper and zinc among multiple sclerosis patients and control group.

BACKGROUND: There have been several studies done on the role of metals in the occurrence of multiple sclerosis (MS) disease, but their roles have not been confirmed yet. Because of the lack of information on this issue, this study compared the serum level of copper and zinc in MS patients with their levels in a control group. METHODS: This was an analytical, cross-sectional study conducted in Kerman (a medium size city), Iran. We assessed the serum level of copper and zinc in 58 MS patients and 39 healthy individuals, who were selected from the relatives of cases and matched for age and sex. RESULTS: The average serum level of Copper in cases and controls were 93.7 and 88.9 ml/dl, respectively. The corresponding numbers for Zinc were 36.7 and 40.9 ml/dl, respectively. There was no significant difference between the two groups (copper: P = 0.459; zinc: P = 0.249). CONCLUSION: The groups were matched for age, sex, and family. However, we did not find a considerable difference between the level of these metals in MS patients and controls.