Development, Optimization, and in vitro Evaluation of Silybin-loaded PLGA Nanoparticles and Decoration with 5TR1 Aptamer for Targeted Delivery to Colorectal Cancer Cells.

Chemotherapeutic agents often lack specificity, intratumoral accumulation, and face drug resistance. Targeted drug delivery systems based on nanoparticles (NPs) mitigate these issues. Poly (lactic-co-glycolic acid) (PLGA) is a well-studied polymer, commonly modified with aptamers (Apts) for cancer diagnosis and therapy. In this study, silybin (SBN), a natural agent with established anticancer properties, was encapsulated into PLGA NPs to control delivery and improve its poor solubility. The field-emission scanning electron microscopy (FE-SEM) showed spherical and uniform morphology of optimum SBN-PLGA NPs with 138.57±1.30nm diameter, 0.202±0.004 polydispersity index (PDI), -16.93±0.45mV zeta potential (ZP), and 70.19±1.63% entrapment efficiency (EE). The results of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) showed no chemical interaction between formulation components, and differential scanning calorimetry (DSC) thermograms confirmed efficient SBN entrapment in the carrier. Then, the optimum formulation was functionalized with 5TR1 Apt for active targeted delivery of SBN to colorectal cancer (CRC) cells in vitro. The SBN-PLGA-5TR1 nanocomplex released SBN at a sustained and constant rate (zero-order kinetic), favoring passive delivery to acidic CRC environments. The MTT assay demonstrated the highest cytotoxicity of the SBN-PLGA-5TR1 nanocomplex in C26 and HT29 cells and no significant cytotoxicity in normal cells. Apoptosis analysis supported these results, showing early apoptosis induction with SBN-PLGA-5TR1 nanocomplex which indicated this agent could cause programmed death more than necrosis. This study presents the first targeted delivery of SBN to cancer cells using Apts. The SBN-PLGA-5TR1 nanocomplex effectively targeted and suppressed CRC cell proliferation, providing valuable insights into CRC treatment without harmful effects on healthy tissues.

Nanohybrid Based on (Mn, Zn) Ferrite Nanoparticles Functionalized With Chitosan and Sodium Alginate for Loading of Curcumin Against Human Breast Cancer Cells.

This study reports on the synthesis of Mn1 - xZnxFe2O4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn0.8Zn0.2Fe2O4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn0.8Zn0.2Fe2O4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded Alg/Chit@Mn0.8Zn0.2Fe2O4 NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems.

Atorvastatin mucoadhesive tablets in the management of recurrent aphthous stomatitis: a randomized clinical study.

BACKGROUND: Aphthous stomatitis is one of the most common oral mucosal diseases. Due to the commonness of recurrent aphthous stomatitis and considering the anti-inflammatory, analgesic, and tissue regenerative properties of atorvastatin and the lack of a study on the effect of statins on minor recurrent aphthous stomatitis, this study investigates the effect of atorvastatin mucoadhesive tablets as a topical treatment on reduction of symptoms and duration of this disease. METHODS: This study is a randomized, double-blinded clinical trial. Patients were divided into two groups, atorvastatin and, placebo; each of the patients received three mucoadhesive tablets daily in the morning, noon, and night. Finally, the patients were examined on days 0 (baseline), 3, 5, and 7 to determine the diameter of the inflammatory halo. The VAS scale was used to evaluate pain intensity for up to 7 days after each meal. The data was entered into SPSS 24 software and analyzed. RESULTS: The halo diameter did not significantly differ between the two groups on baseline (P > 0.05). However, on the study's third, fifth, and seventh days, the difference between the two groups was remarkable, so in the atorvastatin group, the size of the lesions decreased in shorter healing time (P < 0.05). In addition, the patient's pain intensity (VAS) also showed a significant decrease in the atorvastatin group except on the first, second, and seventh days of the study (P < 0.05). CONCLUSION: Atorvastatin mucoadhesive tablets effectively reduce the pain of patients with minor recurrent aphthous stomatitis and reduce the size and healing time of the lesions, so their application should be considered in treating minor recurrent aphthous stomatitis. The present study was approved by the Medical Ethics Committee of Mazandaran University of Medical Sciences with the ethics code IR.MAZUMS.REC.1400.8346. Also, this study received code IRCT20170430033722N4.

Solid lipid nanoparticles and nanostructured lipid carriers: a review of the methods of manufacture and routes of administration.

The bioavailability of drugs is dependent on several factors such as solubility and the administration route. A drug with poor aqueous solubility, therefore, poses challenges with regards to its pharmaceutical advance and ultimately its biological usage. Lipid nanoparticles have been used in pharmaceutical science due to their importance in green chemistry. Their biochemical properties as 'green' materials and biochemical processes as 'green' processes mean they can be environmentally sustainable. Generally, lipid nanoparticles can be employed as carriers for both lipophilic and hydrophilic drugs. The proposed administration route for nanoparticles can present advantages and disadvantages which should be considered by a formulator. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are attractive delivery systems because of their ease of manufacture, biocompatibility, biodegradability, and scale-up capacity of formulation constituents. The easy and simple scalability of novel SLNs and nano lipid carriers, along with their various processing procedures, recent developments, limitation and toxicity, formulation optimization and approaches for the manufacture of lipid nanoparticles, lyophilization and drug release are comprehensively discussed in this review. This review also summarizes the research data related to the various preparation methods and excipients used for SLNs and NLCs in recent years.

Atorvastatin Entrapped Noisome (Atrosome): Green Preparation Approach for Wound Healing.

The present study aimed to formulate atorvastatin niosome (Atrosome) through an ultrasonic technique and to determine its contribution to the extent of wound healing in an animal model. The optimized Atrosome formulation (Atrosome-2) was stable at 4 °C for 3 months. Differential scanning calorimetry (DSC), ATR-Fourier transform infrared spectroscopy (ATR-FTIR), and powder X-ray diffraction (PXRD) analysis revealed that atorvastatin (ATR) was well encapsulated within the niosomes either in a stabilized amorphous form or a molecularly dispersed state. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscope (AFM) confirmed the spherical nature of the Atrosomes. The optimized formulation showed polydispersity index, particle size, drug encapsulation efficiency (EE%), and zeta potential of 0.457 ± 0.05, 196.33 ± 6.45 nm, 86.15 ± 0.58 %, and - 20.73 ± 0.98 mV, respectively. ATR release from the Atrosome gel followed the first-order kinetic model and showed no cytotoxicity in the in vitro cytotoxicity test. Cell viability (human foreskin fibroblast cell line) was nearly 99%. An excision wound model was also applied in male Wistar rats to examine the in vivo efficacy of the optimized formulation, followed by investigating malondialdehyde (MDA, an end-product of lipid peroxidation), superoxide dismutase (SOD, an endogenous antioxidant), hydroxyproline levels, and glutathione peroxidase (GPx) in skin tissue samples. MDA significantly decreased in the Atrosome gel group after 21 days, while GPx, SOD, and hydroxyproline levels demonstrated an increase. According to histological results, rats receiving Atrosomes were treated effectively faster when compared to the other formulation used.

Venlafaxine HCl Encapsulated in Niosome: Green and Eco-friendly Formulation for the Management of Pain.

The goal of this experimentation was to increase the cutaneous absorption of venlafaxine HCl (VFX) encapsulated in a niosome (venlasosme) produced by an ultrasonic approach. The impact of the cholesterol:surfactant (Chol:Surf) proportion was examined to modify the venlasosme properties. Photon correlation spectroscopy, powder X-ray diffraction (PXRD), SEM, DSC, and ATR-FTIR spectroscopy were utilized to investigate the solid-state and morphology of VFX in the venlasosme. The studies revealed that increasing the level of Chol in the venlasosme increased the size of the particles. Alterations in the Chol to surfactant ratios (when Chol decreased from 2.5 to 0%) caused the zeta potential enhancement from 7.37 ± 0.67 to 15.53 ± 1.47 mV. The venlasosme with the highest cholesterol concentration (2.5%) had the highest encapsulation efficiency (approximately 63%). PXRD results revealed that VFX in venlasosme was in the amorphous form. The levels of VFX in the cutaneous layers and the receiver compartment were higher for the venlasosme gel than for VFX simple gel in the cutaneous permeability study and showed no cutaneous irritancy in rats. Furthermore, the venlasosme gel demonstrated significant antinociceptive and anti-inflammatory responses when compared to the control groups (VFX simple gel and diclofenac gel). The topical administration of the venlasosme gel also considerably increased the tail-flick and hot-plate response time when compared to the VFX simple gel, control groups, and diclofenac gel (p < 0.05). These findings suggest that niosomes can improve VFX efficacy as an antinociceptive and anti-inflammatory substance by improving the medicaments delivery to the specified site.

Malus domestica reduces chemotherapy-induced nausea and vomiting: A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is considered as the most common complications of chemotherapy which has a detrimental influence on the quality of life of patients with cancer. We assessed the efficacy of Apple (Malus domestica) syrup for reducing CINV. MATERIALS AND METHODS: This study was a randomized, double-blind, placebo-controlled trial carried out in a Hematooncology Clinic affiliated to Mazandaran University of Medical Sciences, Sari, Iran (from October 2017 to August 2018). Subjects were randomly allocated to receive apple syrup or placebo along with their previous antiemetic treatment and chemotherapy regimen, three times a day. Thirty-four patients received apple syrup (n = 16) or placebo (n = 18). Statistical analysis was conducted using SPSS software Version 21® (SPSS Inc., Chicago, IL, USA). A P < 0.05 indicated statistical significance. RESULTS: Both acute and delayed nausea grades were significantly lower in M. domestica syrup in comparison to placebo syrup (P = 0.001 and 0.001, respectively). The duration of nausea (P = 0.04) was lower in intervention group compared to placebo group. CONCLUSION: These findings demonstrated that M. domestica syrup can reduce the severity and duration of nausea in cancer patients who received chemotherapy.

Atorvastatin Solid Lipid Nanoparticles as a Promising Approach for Dermal Delivery and an Anti-inflammatory Agent.

In the current research, the main focus was to overcome dermal delivery problems of atorvastatin. To this end, atorvastatin solid lipid nanoparticles (ATR-SLNs) were prepared by ultra-sonication technique. The prepared SLNs had a PDI value of ≤ 0.5, and the particle size of nanoparticles was in the range 71.07 ± 1.72 to 202.07 ± 8.40 nm. It was noticed that, when the concentration of lipid in ATR-SLNs increased, the size of nanoparticles and drug entrapment efficiency were also increased. Results showed that a reduction in the HLB of surfactants used in the preparation of SLN caused an increase in the particle size, zeta potential (better stability), and drug entrapment efficiency. Despite Tween and Span are non-ionic surfactants, SLNs containing these surfactants showed a negative zeta potential, and the absolute zeta potential increased when the concentration of Span 80 was at maximum. DSC thermograms, FTIR spectra, and x-ray diffraction (PXRD) pattern showed good incorporation of ATR in the nanoparticles without any chemical interaction. In vitro skin permeation results showed that SLN containing atorvastatin was capable of enhancing the dermal delivery of atorvastatin where a higher concentration of atorvastatin can be detected in skin layers. This is a hopeful promise which could be developed for clinical studies of the dermal delivery of atorvastatin nanoparticles as an anti-inflammatory agent.

Evaluation of zinc sulfate mucoadhesive formulation on recurrent aphthous stomatitis: a randomized double-blind, placebo-controlled clinical trial.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common lesion that affects the oral mucosa. There are several methods to treat RAS, including systemic and topical formulations. This study was conducted to evaluate the anti-inflammatory effect of topical zinc sulfate and its efficacy in the treatment of RAS. METHODS: A double-blind randomized clinical trial was conducted on 46 patients with RAS. They were randomly assigned into two groups to receive a zinc sulfate mucoadhesive tablet or placebo for 7 days. The pain severity was measured at baseline and daily while the diameter of the lesion was measured at baseline and on days 3, 5, and 7. The obtained data were analyzed in SPSS V.16. RESULTS: There was no significant difference in the mean diameter of lesions and pain at baseline between the two groups (P = 0.643 and P = 0.842, respectively). However, on the third, fifth, and seventh days of the study, the diameter of the lesion significantly reduced in the intervention group (P = 0.001) and the pain intensity became significantly different between groups from the fourth day of the study (P = 0.001). CONCLUSION: Zinc sulfate mucoadhesive tablet was effective in recovery and reducing the pain and diameter of the aphthous lesion and could be considered for the treatment of RAS. TRIAL REGISTRATION: Evaluation of the effectiveness of zinc sulfate mucoadhesive tablet in the improvement of recurrent aphthous stomatitis (RAS), IRCT20151109024975N9. Registered August 1, 2018, https://en.irct.ir/trial/32423 . This project was registered by the Iranian Registry of Clinical Trials ( http://www.irct.ir ). The IRCT ID was IRCT20151109024975N9.

Topical atorvastatin 1% for prevention of skin toxicity in patients receiving radiation therapy for breast cancer: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: The purpose of this randomized, placebo-controlled, double-blind study was to investigate the preventive effect of topical administration of atorvastatin (ATV) on the acute radiation-induced skin toxicity in patients with breast cancer. PATIENTS AND METHODS: Seventy breast cancer patients were randomly assigned to use topical ATV 1% or placebo gels during radiotherapy twice daily. Radiation-induced dermatitis was classified according to the radiation therapy oncology group (RTOG) criteria, as well as pain and itching were scored according to VAS (visual analogue scale) for 6 weeks of treatment. RESULTS: Topical administration of ATV gel during radiotherapy reduced significantly radiation-induced breast swelling, itching, and pain in breast cancer patients by factors of 1.8, 1.7, and 1.5, respectively. ATV reduced the redness caused by radiotherapy in patients as compared with placebo; however, this difference was statistically not significant. CONCLUSION: ATV was able to reduce significantly itching, breast edema, and pain in patients during radiotherapy.

The effectiveness of Zataria extract mouthwash for the management of radiation-induced oral mucositis in patients: a randomized placebo-controlled double-blind study.

OBJECTIVES: Oral mucositis (OM) is a common debilitating complication of chemoradiotherapy treatment of head and neck cancers. This randomized placebo-controlled double-blind clinical trial study was performed to evaluate the effectiveness of Zataria multiflora (ZM) extract mouthwash in the prevention and reduction of OM related to local radiotherapy in the treatment of head and neck cancer patients. METHODS: Sixty-three patients with head and neck cancers, who underwent a conventional fractionated radiotherapy regimen, were entered into the study. Patients gargled the ZM mouthwash or a placebo before the beginning of the treatment three times daily and before each radiotherapy session. The assessment of OM was conducted according to WHO and Oral Mucositis Assessment Scale. RESULTS: The OM intensity trends in the ZM group during these weeks of treatment were detected 3.152 times less frequently than in the placebo group. A twofold decrease in the incidence of grades 3-4 OM was observed in the ZM group compared to the placebo. The use of the ZM mouthwash affected the incidence of grades 3-4 OM to a relative risk ratio of 0.432. The pain score was significantly decreased in the ZM group compared to the placebo group. CONCLUSION: The present study revealed that ZM mouthwash effectively decreases the severity of OM and mouth pain in patients with head and neck cancer treated with radiotherapy. CLINICAL RELEVANCE: The use of ZM mouthwash effectively decreases the severity of oral complications induced by ionizing radiation in patients during radiotherapy and resulted in high oral quality care. Graphical abstract ᅟ.

Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability.

BACKGROUND: We assessed the feasibility of using crystal-liquid fugacity ratio (CLFR) as an alternative parameter for intestinal permeability in the biopharmaceutical classification (BCS) of passively absorbed drugs. METHODS: Dose number, fraction of dose absorbed, intestinal permeability, and intrinsic dissolution rate were used as the input parameters. CLFR was determined using thermodynamic parameters i.e., melting point, molar fusion enthalpy, and entropy of drug molecules obtained using differential scanning calorimetry. RESULTS: The CLFR values were in the range of 0.06-41.76 mole percent. There was a close relationship between CLFR and in vivo intestinal permeability (r > 0.8). CLFR values of greater than 2 mole percent corresponded to complete intestinal absorption. Applying CLFR versus dose number or intrinsic dissolution rate, more than 92% of tested drugs were correctly classified with respect to the reported classification system on the basis of human intestinal permeability and solubility. CONCLUSION: This investigation revealed that the CLFR might be an appropriate parameter for quantitative biopharmaceutical classification. This could be attributed to the fact that CLFR could be a measure of solubility of compounds in lipid bilayer which was found in this study to be directly proportional to the intestinal permeability of compounds. This classification enables researchers to define characteristics for intestinal absorption of all four BCS drug classes using suitable cutoff points for both intrinsic dissolution rate and crystal-liquid fugacity ratio. Therefore, it may be used as a surrogate for permeability studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Transdermal absorption enhancing effect of the essential oil of Rosmarinus officinalis on percutaneous absorption of Na diclofenac from topical gel.

CONTEXT: Rosemary essential oil has been used topically for several purposes (analgesic, anti acne, and anti-inflammatory) in Iranian traditional medicine. OBJECTIVES: This investigation aimed to study the effect of essential oil of Rosmarinus officinalis L. (Lamiaceae) on the transdermal absorption of Na diclofenac from topical gel. MATERIAL AND METHODS: Diclofenac sodium topical gel was prepared with HPMC K4M and Carbopol 934P as a gelling agent, and several vehicles. The most stable gel was chosen and enhancing effects of the essential oil with different concentrations (0.1, 0.5, and 1.0% w/w) on the permeation of diclofenac were evaluated. The anti-nociceptive effect of preparations was evaluated based on the formalin and tail flick tests in mice. RESULTS: The major constituents of the essential oil were 1,8-cineol (15.96%), α-pinene (13.38%), camphor (7.87%), bornyl acetate (6.54%), verbenone (5.82%), borneol (5.23%), camphene (4.96%), and (E)-caryophyllene (3.8%). Topical diclofenac containing 0.5% essential oil showed more analgesic effect after 25, 30, and 35 min (p < 0.001) than the reference drug in the tail flick test. The analgesic effect of preparation containing 1% essential oil was more than reference gel after 15 min (p < 0.05). This difference was observed after 20, 25, 30, 35, and 40 min (p < 0.001) too. Rosemary essential oil 1% promoted analgesic effect of drug in comparison with diclofenac gel in the formalin early phase (p < 0.05). The enhancing effect of rosemary was observed in 0.5 and 1% concentration (p < 0.05 and p < 0.001, respectively) in the late phase. CONCLUSION: This study proved the enhancing effect of 0.5 and 1% of rosemary essential oil on diclofenac percutaneous absorption.

Development of kojic acid loaded collagen-chitosan nanoparticle as skin lightener product: in vitro and in vivo assessment.

In the present study, an ionic gelation and ultrasonic approach was performed to produce kojic acid (KA) loaded chitosan(CS)/collagen(CN) nanoparticle(NP) (CSCN-NP) which aimed to increase the dermal delivery and anti-pigmentation effect. To optimize the CSCN-NP the effect of the amount of CN was investigated. The results showed that increasing CN from 0 to 500 mg increased the mean particle size and entrapment efficiency of KA-CSCN-NP from 266.07 ± 9.30 nm to 404.23 ± 9.44 nm and 17.37 ± 2.06% to 82.34 ± 2.16%, respectively. Differential scanning calorimetry confirmed the amorphous form of KA in CSCN-NP, while scanning electron microscopy revealed that the nanoparticles were spherical. There was no chemical interaction between KA and the other components base on attenuated total reflectance-Fourier transform infrared spectroscopy. The skin permeability test showed that KA-CSCN-NP gel delivered more KA to the dermal layers (29.16 ± 1.67% or 537.26 ± 537.26 µg/cm2) and receiver compartment (15.04 ± 1.47% or 277.15 ± 27.22 µg/cm2) compared to KA plain gel. In vitro cytotoxicity assay demonstrated that the improved KA-CSCN-NP was non-toxic. Dermal irritating test on Wistar rats showed that the KA gel was non-irritating. Furthermore, KA-CSCN-NP was found to inhibit melanin formation to a greater extent than free KA and significantly inhibited L-dopa auto-oxidation (94.80 ± 2.41%) compared to pure kojic acid solution (75.28 ± 3.22%). The observations of this study revealed that the produced KA-CSCN-NP might be used as a potential nano-vehicle for KA dermal administration, thereby opening up innovative options for the management of hyper-melanogenesis problems.

Green Formulation of Spironolactone Loaded Chitosan-Coated Nano Lipid Carrier for Treatment of Acne Vulgaris: A Randomized Double-Blind Clinical Trial.

Purpose: Spironolactone (SPN), which is classified as an anti-androgen, has demonstrated efficacy in treating acne. This study aimed to utilize ultrasonication to create a chitosan-coated nano lipid carrier (NLC) for enhancing the delivery of SPN to the skin and treating acne. Methods: Various hydrophilic-lipophilic balance (HLB) values were investigated to optimize the SPN-NLCs. Photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were employed to characterize the solid state of SPN in nanoparticle form. Additionally, the optimized formulation was used in a double-blind, randomized clinical trial. Results: Reducing the HLB of the surfactant mixtures resulted in a reduction in the size of SPNNLCs. The formula with the smallest particle diameter (238.4±0.74 nm) and the lowest HLB value (9.65) exhibited the highest encapsulation efficiency (EE) of 79.88±1.807%. Coating the optimized SPN-NLC with chitosan increased the diameter, polydispersity index (PDI), zeta potential (ZP), and EE. In vitro skin absorption studies demonstrated sustained release profiles for chitosan-coated SPN-NLC. In the double-blind trial, a gel containing chitosan-coated SPN-NLC effectively treated mild to moderate acne vulgaris, leading to improved healing and reduced lesion count after 8 weeks of therapy compared to the placebo. It successfully addressed both non-inflammatory and inflammatory lesions without adverse effects on the skin. Conclusion: The findings indicate that chitosan-coated SPN-NLCs have the potential as nanoparticles for targeted SPN delivery to the skin, offering novel options for the treatment of acne vulgaris.

Purification and biochemical characterization of an acidophilic amylase from a newly isolated Bacillus sp. DR90.

An acidophilic and Ca(2+)-independent amylase was purified from a newly isolated Bacillus sp. DR90 by ion-exchange chromatography, and exhibited a molecular weight of 68.9 kDa by SDS-PAGE. The optimum pH and temperature of the enzyme were found to be 4.0 and 45 °C, respectively. The enzyme activity was increased by Ba(2+), Fe(2+) and Mg(2+), and decreased by Hg(2+) and Zn(2+), while it was not affected by Na(+), K(+), phenylmethylsulfonyl fluoride and ß-mercaptoethanol. Ca(2+) and EDTA did not have significant effect on the enzyme activity and thermal stability. The values of K m and V max for starch as substrate were 4.5 ± 0.13 mg/ml and 307 ± 12 µM/min/mg, respectively. N,N-dialkylimidazolium-based ionic liquids such as 1-hexyl-3-methylimidazolium bromide [HMIM][Br] have inhibitory effect on the enzyme activity. Thin layer chromatography analyses displayed that maltose and glucose are the main products of the enzyme reaction on starch. Regarding the features of the enzyme, it may be utilized as a novel candidate for industrial applications.

Efficacy of Oral Mucoadhesive N-Acetylcysteine Tablets in Treatment of Recurrent Aphthous Stomatitis: A Randomized Double-Blind, Placebo-Controlled Clinical Trial.

Objectives: This study aimed to assess the efficacy of oral mucoadhesive N-acetylcysteine (NAC) tablets for treatment of recurrent aphthous stomatitis (RAS). Materials and Methods: Forty-nine patients with RAS were randomized to receive mucoadhesive NAC tablets (n=25) or placebo (n=24). Tablets were prescribed three times a day for 7 days in each group. Pain intensity was evaluated with visual analog scale (VAS) three times a day from day 1 to day 7. Also, patients were clinically examined on days 0 (before entering the study), 3, 5, and 7 using a metal caliper to measure the diameter of the lesions. The data were statistically analyzed and P<0.05 was considered statistically significant. Results: Regarding the VAS score, all participants in the treatment group showed complete recovery on day 7 (P<0.01). Also, the diameter of the lesions was significantly smaller in the treatment group than the placebo group at the end of the study (P<0.001). Conclusion: The results of this clinical trial showed for the first time that mucoadhesive NAC tablets can significantly decrease pain and the diameter of RAS lesions without any systemic complications.

Safety and Health Management System, Safety Climate, and Accident Occurrences in Hospitals: The Study of Needlestick, Sharp Injuries and Recidivism Rates.

Background: Hospital Safety and Health Management System (HSH-MS) and Hospital Safety Climate (HSC) are the significant elements to develop safe work practices. The current study aimed to examine the dimensions of HSH-MS and HSC and the association with the prevalence of Needlestick and Sharp Injury (NSI) and NSI recidivism. Materials and Methods: A cross-sectional study was conducted among 1070 nurses in Iranian hospitals (89% response rate). Results: More than 54% (n = 579) had sustained at least 1 NSI in the previous year. The NSI recidivism rate was 8.6% and recidivists were more likely to be younger, female, married, with higher Body Mass Index (BMI), and on night shift. Two aspects of HSH-MS including management leadership and employee participation were associated with the incidence of NSIs Odds Ratio (OR): 1.91 and 95% Confidence Interval (CI): 0.69-1.21; OR: 1.29 and 95% CI: 0.92-1.82) and NSI recidivism rate (OR: 1.98 and 95% CI: 0.55-1.74; OR: 1.12 and 95% CI: 0.83-1.49). Furthermore, three dimensions of HSC comprising management support (OR: 1.02 and 95% CI: 0.93-1.11 for NSIs; OR: 1.21 and 95% CI: 0.77-1.22 for NSI recidivism), absence of job hindrances (OR: 1.06 and 95% CI: 0.98-1.16 for NSIs; OR: 1.11 and 95% CI: 0.96-1.30 for NSI recidivism) and cleanliness/orderliness (OR: 1.07 and 95% CI: 0.98-1.08 for NSIs; OR: 0.84 and 95% CI: 0.87-0.97 for NSI recidivism) were correlated with reduced NSIs risk. Conclusions: This study suggests that HSH-MSs and employees' safety climate are significant factors, which are correlated with not only the prevalence of recurrent NSIs but also the single NSI in hospitals.

Development of dual-functional core-shell electrospun mats with controlled release of anti-inflammatory and anti-bacterial agents for the treatment of corneal alkali burn injuries.

In this study, a novel dual-drug carrier for the co-administration of an anti-inflammatory and antibiotic agent consisting of core-shell nanofibers for the treatment of cornea alkali burns was designed. The core-shell nanofibers were prepared via coaxial electrospinning of curcumin-loaded silk fibroin as the core and vancomycin-loaded chitosan/polyvinyl alcohol (PVA) as the shell. Electron microscopy (SEM and TEM) images confirmed the preparation of smooth, bead-free, and continuous fibers that formed clear core-shell structures. For further studies, nanofiber mats were cross-linked by heat treatment to avoid rapid disintegration in water and improve both mechanical properties and drug release. The release profile of curcumin and vancomycin indicated an initial burst release, continued by the extended release of both drugs within 72 hours. Rabbit corneal cells demonstrated high rates of proliferation when evaluated using a cell metabolism assay. Finally, the therapeutic efficiency of core/shell nanofibers in healing cornea alkali burn was studied by microscopic and macroscopic observation, fluorescence staining, and hematoxylin-eosin assay on rabbit eyes. The anti-inflammatory activity of fabricated fibers was evaluated by enzyme-linked immunosorbent assay and Immunofluorescence analysis. In conclusion, using a robust array of in vitro and in vivo experiments this study demonstrated the ability of the dual-drug carriers to promote corneal re-epithelialization, minimize inflammation, and inhibit corneal neovascularization. Since these parameters are critical to the healing of corneal wounds from alkali burns, we suggest that this discovery represents a promising future therapeutic agent that warrants further study in humans.