Investigation of the solubility and thermodynamics of salicylic acid in 2-propanol and ethylene glycol/propylene glycol binary solvent mixtures at (293.15 to 313.15) K.

This study aimed to measure both the solubility and thermodynamics of salicylic acid in binary solvent mixtures of (2-propanol + ethylene glycol) and (2-propanol + propylene glycol) at different temperatures in the range of 293.2-313.2 K. The experimental solubility data were analyzed using various linear and nonlinear cosolvency models, such as the van'tt Hoff, Jouyban-Acree, Jouyban-Acree-van'tt Hoff, mixture response surface and modified Wilson models and to evaluate the models, the mean relative deviations of the back-calculated solubility data were compared with experimental values. Through this analysis, the apparent thermodynamic parameters, including Gibbs energy, enthalpy, and entropy were calculated using the van'tt Hoff and Gibbs equations for this system. Additionally, the density values for salicylic acid saturated mixtures were also measured and represent mathematically using the Jouyban-Acree model.

Solubility and thermodynamics properties of salicylic acid in binary mixtures 1-propanol and propylene glycol/ethylene glycol monomethyl ether at different temperatures.

The research aimed to investigate the solubility and thermodynamics of salicylic acid in two binary solvent mixtures of (1-propanol+propylene glycol) and (ethylene glycol monomethyl ether+1-propanol). The study was conducted in the temperature range of 293.2 to 313.2K. To analyze the experimental solubility data, several linear and nonlinear cosolvency models, such as the van't Hoff, Jouyban-Acree, Jouyban-Acree-van't Hoff, mixture response surface, and modified Wilson models were employed. The models' effectiveness was evaluated by comparing the mean relative deviations of the back-calculated solubility data to the experimental values. In addition, the apparent thermodynamic parameters, including Gibbs energy, enthalpy, and entropy, were calculated using the van't Hoff and Gibbs equations. Furthermore, the study measured the density values for salicylic acid-saturated mixtures and represented them mathematically through the Jouyban-Acree model.

Injectable hydrogels for cartilage and bone tissue regeneration: A review.

Annually, millions of patients suffer from irreversible injury owing to the loss or failure of an organ or tissue caused by accident, aging, or disease. The combination of injectable hydrogels and the science of stem cells have emerged to address this persistent issue in society by generating minimally invasive treatments to augment tissue function. Hydrogels are composed of a cross-linked network of polymers that exhibit a high-water retention capacity, thereby mimicking the wet environment of native cells. Due to their inherent mechanical softness, hydrogels can be used as needle-injectable stem cell carrier materials to mend tissue defects. Hydrogels are made of different natural or synthetic polymers, displaying a broad portfolio of eligible properties, which include biocompatibility, low cytotoxicity, shear-thinning properties as well as tunable biological and physicochemical properties. Presently, novel ongoing developments and native-like hydrogels are increasingly being used broadly to improve the quality of life of those with disabling tissue-related diseases. The present review outlines various future and in-vitro applications of injectable hydrogel-based biomaterials, focusing on the newest ongoing developments of in-situ forming injectable hydrogels for bone and cartilage tissue engineering purposes.

Enhancing the function of PLGA-collagen scaffold by incorporating TGF-ß1-loaded PLGA-PEG-PLGA nanoparticles for cartilage tissue engineering using human dental pulp stem cells.

Since cartilage has a limited capacity for self-regeneration, treating cartilage degenerative disorders is a long-standing difficulty in orthopedic medicine. Researchers have scrutinized cartilage tissue regeneration to handle the deficiency of cartilage restoration capacity. This investigation proposed to compose an innovative nanocomposite biomaterial that enhances growth factor delivery to the injured cartilage site. Here, we describe the design and development of the biocompatible poly(lactide-co-glycolide) acid-collagen/poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-collagen/PLGA-PEG-PLGA) nanocomposite hydrogel containing transforming growth factor-ß1 (TGF-ß1). PLGA-PEG-PLGA nanoparticles were employed as a delivery system embedding TGF-ß1 as an articular cartilage repair therapeutic agent. This study evaluates various physicochemical aspects of fabricated scaffolds by 1HNMR, FT-IR, SEM, BET, and DLS methods. The physicochemical features of the developed scaffolds, including porosity, density, degradation, swelling ratio, mechanical properties, morphologies, BET, ELISA, and cytotoxicity were assessed. The cell viability was investigated with the MTT test. Chondrogenic differentiation was assessed via Alcian blue staining and RT-PCR. In real-time PCR testing, the expression of Sox-9, collagen type II, and aggrecan genes was monitored. According to the results, human dental pulp stem cells (hDPSCs) exhibited high adhesion, proliferation, and differentiation on PLGA-collagen/PLGA-PEG-PLGA-TGFß1 nanocomposite scaffolds compared to the control groups. SEM images displayed suitable cell adhesion and distribution of hDPSCs throughout the scaffolds. RT-PCR assay data displayed that TGF-ß1 loaded PLGA-PEG-PLGA nanoparticles puts forward chondroblast differentiation in hDPSCs through the expression of chondrogenic genes. The findings revealed that PLGA-collagen/PLGA-PEG-PLGA-TGF-ß1 nanocomposite hydrogel can be utilized as a supportive platform to support hDPSCs differentiation by implementing specific physio-chemical features.

Novel nanocomposite scaffold based on gelatin/PLGA-PEG-PLGA hydrogels embedded with TGF-ß1 for chondrogenic differentiation of human dental pulp stem cells in vitro.

In the current study, a novel nanocomposite hydrogel scaffold comprising of natural-based gelatin and synthetic-based (poly D, L (lactide-co-glycolide) -b- poly (ethylene glycol)-b- poly D, L (lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was developed and loaded with transforming growth factor- ß1 (TGF-ß1). Synthesized scaffolds' chemical structure was examined by 1H NMR and ATR-FTIR. Scanning electron microscopy (SEM) confirmed particle size and morphology of the prepared nanoparticles as well as the scaffolds. The morphology analysis revealed a porous interconnected structure throughout the scaffold with a pore size dimension of about 202.05 µm. The swelling behavior, in vitro degradation, mechanical properties, density, and porosity were also evaluated. Phalloidin/DAPI staining was utilized for confirming the extended cytoskeleton of the chondrocytes. Alcian blue staining was conducted to determine cartilaginous matrix sulfated glycosaminoglycan (sGAG) synthesis. Eventually, over a period of 21 days, a real-time RT-PCR analysis was applied to measure the mRNA expression of chondrogenic marker genes, type-II collagen, SOX 9, and aggrecan, in hDPSCs cultured for up to 21 days to study the influence of gelatin/PLGA-PEG-PLGA-TGF-ß1 hydrogels on hDPSCs. The findings of the cell-encapsulating hydrogels analysis suggested that the adhesion, viability, and chondrogenic differentiation of hDPSCs improved by gelatin/PLGA-PEG-PLGA-TGF-ß1 nanocomposite hydrogels. These data supported the conclusion that gelatin/PLGA-PEG-PLGA-TGF-ß1 nanocomposite hydrogels render the features that allow thein vitrofunctionality of encapsulated hDPSCs and hence can contribute the basis for new effective strategies for the treatment of cartilage injuries.

Molecular mechanism and thermodynamic study of Rosuvastatin interaction with human serum albumin using a surface plasmon resonance method combined with a multi-spectroscopic, and molecular modeling approach.

Rosuvastatin (ROS) is an anti-cholesterol drug belonging to statin drugs. A multi-spectroscopic approach combined with a molecular modeling technique was used to assess ROS association with human serum albumin (HSA). Besides, an HSA immobilized surface plasmon resonance (SPR) chip was used to obtain kinetic parameters (ka, kd, and KD). Fluorescence quenching titrations revealed that ROS interacts with HSA via a dynamic, exothermic, enthalpy-driven mechanism. Hydrogen bonds and van der Waals interactions as the most prevalent bonding forces contribute to ROS-HSA complex formation. ROS binding to HSA alters HSA conformation. The SPR results indicated that ROS and HSA have a strong interaction possessing an equilibrium constant (KD) of 1.55 × 10-8 M at 298 K. A competitive analysis of site markers showed that ROS has a higher tendency to bind to the warfarin binding site (site IIA), which may explain why warfarin has a higher anticoagulant effect in ROS users. FRET analysis indicated that non-radiation energy transfer occurred between ROS and HSA. According to molecular docking studies, ROS prefers binding sites IB and IIA while the ROS-HSA complex stabilizes due to the hydrogen bond and π-π interaction. The presence of hydrogen-bond donors and acceptors, as well as aromatic ROS moieties, facilitates such interactions.

Synthesis and characterization of new surface modified magnetic nanoparticles and application for the extraction of letrozole from human plasma and analysis with HPLC-fluorescence.

Acetic acid-functionalized magnetic nanoparticles modified by (3-amino-propyl)-tri-ethoxy silane was synthesized and used as a new solid-phases adsorbent. Infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), x-ray diffraction (XRD), energy-dispersive x-ray spectroscopy (EDX), vibrating sample magnetometer (VSM) and Electrophoretic Light Scattering (ELS) were used to characterize the modified nanoparticles. The molecular interaction between letrozole and nanoparticles (NPs) was studied using density functional theory (DFT) calculations. The developed nanoparticles were applied for dispersive solid-phase extraction of letrozole (an anticancer drug) from human plasma. Extracted letrozole was quantified using an isocratic HPLC/FL method. The extraction efficiency was optimized using one experiment at a time optimization method based on the adsorbent quantity, sample pH, adsorption time, desorption time, and elution solvent type/volume. The analysis method was fully validated according to the FDA guideline for bioanalytical method validation. The linear quantification range was 0.01-1 µg/mL and the lower limit of quantification (LLOQ) was 0.01 µg/mL. Plasma samples of 6 patients were analyzed and the measured letrozole concentrations range was 0.04-0.31 µg/mL. The newly synthesized magnetic nanoparticles were used successfully for the extraction of letrozole from spiked and clinical plasma samples. The developed method is a precise and simple method that is suitable for pharmacokinetic studies and clinical applications.

Comparison of General Dentistry Curriculum in Iran with Eight of the World's Top Dental Faculties.

Background and objectives:A curriculum is a general and immense outline of an educational activity. A curriculum defines teaching content, student and curriculum assessment methods, and ultimately defines the framework for each activity in the curriculum. Given the importance of training in medicine and dentistry, the purpose of this study was to compare Iran's general dentistry curriculum with eight of the world's top dental faculties. Materials and methods:In descriptive-comparative research, the important components and parameters of the curriculum of the PhD in dentistry at several universities in the world were studied and compared with Iranian curriculum. The present study was conducted in two stages: The first phase included finding the best dental faculties in the world; the second phase was to identify and examine the various components of the curriculum of the PhD in Public Dentistry in Iran and the 8th highest dental faculties in the world and compare them according to Loudvigsson indicators. The results of the study were reported using descriptive statistics (frequency and percentage). Results:All of the evaluated indicators were in the Iranian curriculum. The study of the eight top universities in the world showed that the indicators worth paying attention to, including critical thinking and scientific approach in the program, student-centered curriculum, horizontal and vertical integration, systematic education, education based on community health care system, community-based education and ethical principles, existed in all curricula of the studied colleges. The presence of a selective framework in a curriculum and early clinical exposure was only available in the educational curriculum of four universities: Toronto, UNC, Minnesota and UCLA. The focus on small group work was defined as the prevailing educational method in three Herman Ostrow, Minnesota and UCSF universities. The problem-solving learning index was only presented at two universities in Osaka and NYU. Conclusion:The highest rates of Loudvigsson indicators in general dentistry curriculums of eight universities in the world were 90% and at least 72.7%, while the above indicators were 100% in the dentistry curriculum of Iran. According to the indicators of Loudvigsson, Iran's dental training program is ranked high in content.

Health Complex Model as the Start of a New Primary Healthcare Reform in Iran: Part B: The Intervention Protocol.

BACKGROUND: For overcoming the existing problems and finding a pathway for realization of universal health care, health complexes were implemented in the form of a pilot project in Tabriz suburban area. METHODS: Tabriz Health Complex Project was designed in 2013 in the provincial health center of East Azerbaijan. In terms of execution schedule, this intervention had 4 phases including 1) study phase, 2) planning phase, 3) pilot phase, and 4) implementation phase. Each health complex covers a population of 40,000 to 120,000 in a defined geographic area and consists of a Comprehensive Health Center (CHC) including health centers and a management center, which usually located in CHC. The important features of this project are as follows: people-centered primary health care, special attention to health promotion and prevention and establishment of a referral system within the region (organic connection between the first and second levels). RESULTS: An accountable and responsive health care system has been established to deliver integrated care services to people in a defined catchment area against identified per capita payment, under district health centre policies and regulations. Each health team consisted of a general practitioner and a family health nurse who covered around 4000 people to deliver prevention, promotion, and treatment services especially in and NCDs field. CONCLUSION: Health complex as a model of public-private participation and practical solution to address many of the problems in the primary care system of the country. The project can organize the PHC system and family medicine program.

Calculating reading ease score of patient package inserts in Iran.

BACKGROUND: The patient package inserts (PPIs), which contain the necessary information about medications intended for patients, need to be expressed in a clear language comprehensible to everyone. OBJECTIVE: This study aimed to evaluate the readability and understandability of the drug package inserts for the inexpert people. METHODS: The readability of the 158 PPIs of the 33 drugs, registered and manufactured in Iran, was calculated. The main criterion for selecting PPIs to include in this study was of those top-selling drugs during the year 2015 according to the Social Security Organization in Iran. The PPIs were collected from the pharmacies of the three major cities, namely, Tabriz, Ardabil and Meshgin Shahr. Then, using the Flesch-Dayani readability (FDR) tool adjusted for the Persian language, the average number of the words and syllables was counted to calculate and grade the readability score of the selected PPIs. RESULTS: This study showed that the average FDR readability score for all the 33 drugs is 52.52, which are graded 10th-11th. Of the PPIs, 70.89% were difficult to read, and on average, the readability of the PPIs was five times difficult than the standard ones. Only 13.92% PPIs were suitable for the 5th-7th grade, and 15.19% of the package inserts ranked in the 8th-9th reading grade. CONCLUSION: A considerable number of the PPIs in Iran have low readability level and were not suitable for the inexpert readers. Since the treatment cost is very high, people tend to use medications arbitrarily or simply use old prescriptions. This study suggests the necessity of a major improvement in the readability level of the PPIs in order to ensure the usefulness of the PPIs to the majority of the consumers.

Protective effect of soy protein on collagen-induced arthritis in rat.

To evaluate preventive and therapeutic effects of soy protein on collagen-induced arthritis rats. Sprague-Dawley rats immunized with bovine type II collagen emulsified in adjuvant and treated with soy protein (7 g/kg), dexamethasone (1 mg/kg), and casein (in control groups) by daily gavages feedings for 30 days. Score of arthritis recorded every day for each paws of animal. Tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin were measured in serums. Treatment with soy protein resulted in significant delay in time to onset of arthritis as well as significantly decreased arthritis incidence, clinical arthritis severity score, histopathological arthritis severity score, and in vivo cell-mediated immunity to collagen (P < 0.05). Administration of soy protein significantly suppressed the progression of collagen II-induced arthritis and inhibited the production of tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin. Soy protein appeared to be a potent immunomodulatory inhibitor of collagen II-induced arthritis in rats. It could delay onset of RA and reduced cartilage erosion and synovitis inflammation. Therefore, it may be a useful protein in the prevention and treatment of rheumatoid arthritis patient.

Influence of a high cholesterol regime on epicardial and subcutaneous adipose tissue fatty acids profile in rabbits.

BACKGROUND: We have shown that the fatty acid profile of epicardial adipose tissue (EAT) in patients with obstructed coronary vessels is different from that of the subcutaneous adipose tissue (SAT). The diversity and amount of fatty acids in the adipose tissue can be affected by the component of the lipids in diet. As a result, this study investigated the influence of a high cholesterol regime on EAT and subcutaneous adipose tissue fatty acids profile in rabbits. METHODS: Sixteen New Zealand white rabbits were randomly divided into two equal groups. The control group received a normal standard diet, whereas the test group was fed with the high cholesterol regime for 2 months. At the end of this period, the rabbits were anesthetized, 1-5 mg of EAT and SAT were removed, and their fatty acids content was determined. RESULTS: The high cholesterol regime caused a significant increase in low-density lipoprotein (LDL) and triglycerides levels and a marked decrease in high-density lipoprotein (HDL) concentration. After 2 months, in the EAT, fatty acids 16:0 and 18:1t and saturated fatty acid (SFA) showed a significant increase (P<0.05), whereas, fatty acids 12:0, 18:1, 18:2, and 18:3, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), ω3, and ω6 had a significant decrease (P<0.05). In SAT, fatty acids 18:3, 20:4, 22:6, MUFA, and ω3 decreased and PUFA, SFA, and ω6 significantly increased (P<0.05). CONCLUSION: Consumption of a high cholesterol regime for 2 months resulted in a significant increase in atherogenic fatty acids and a decrease in antiatherogenic ones in the EAT. EAT is very sensitive to lipid changes of the regime comparing to SAT.

A highly sensitive RP-HPLC-fluorescence method to study aldehyde oxidase activity.

Aldehyde oxidase is a widely distributed enzyme that is involved in the metabolism of an extensive range of aldehydes and N-heterocyclic compounds with physiological, pharmacological, and toxicological relevance. In the present study, a highly sensitive RP-HPLC-fluorescence method based on the oxidation of phenanthridine to phenanthridinone has been developed and validated to assay aldehyde oxidase activity in biological samples. Determination of phenanthridinone was achieved on a C18 column using 10 mmol/L phosphate buffer (pH 5.0) containing 0.1 mmol/L EDTA-acetonitrile (40 + 60, v/v) as the mobile phase. The fluorescence intensity of phenanthridinone was measured at 364 nm with excitation at 236 nm. The proposed method was precise, accurate, specific and rapid (analysis time, approximately 8 min) with a mean RSD of 2.54%. Peak responses were linear from 0.5 to 100 nmol/L, with an LOD of 0.125 nmol/L. The applicability of the method was demonstrated by measurement of aldehyde oxidase activity in rat liver, kidney, ovary, and heart fractions.

A new multi-wavelength model-based method for determination of enzyme kinetic parameters.

Lineweaver-Burk plot analysis is the most widely used method to determine enzyme kinetic parameters. In the spectrophotometric determination of enzyme activity using the Lineweaver-Burk plot, it is necessary to find a wavelength at which only the substrate or the product has absorbance without any spectroscopic interference of the other reaction components. Moreover, in this method, different initial concentrations of the substrate should be used to obtain the initial velocities required for Lineweaver-Burk plot analysis. In the present work, a multi-wavelength model-based method has been developed and validated to determine Michaelis-Menten constants for some enzyme reactions. In this method, a selective wavelength region and several experiments with different initial concentrations of the substrate are not required. The absorbance data of the kinetic assays are fitted by non-linear regression coupled to the numeric integration of the related differential equation. To indicate the applicability of the proposed method, the Michaelis-Menten constants for the oxidation of phenanthridine, 6-deoxypenciclovir and xanthine by molybdenum hydroxylases were determined using only a single initial concentration of the substrate, regardless of any spectral overlap.

Inhibitory effects of flavonoids on aldehyde oxidase activity.

Flavonoids are an important group of natural compounds that can interfere with the activity of some enzymes. In this study, effects of various flavonoids on aldehyde oxidase (AO) activity were evaluated in vitro. AO was partially purified from guinea pig liver. The effects of 12 flavonoids from three subclasses of flavon-3-ol, flavan-3-ol and flavanone on the oxidation of vanillin and phenanthridine as substrates of AO and xanthine as a substrate of xanthine oxidase (XO) were investigated spectrophotometrically. Among the 12 flavonoids, myricetin and quercetin were the most potent inhibitors of both AO and XO. In general, the oxidation of vanillin was more inhibited by flavonoids than that of phenanthridine. Almost all of the flavonoids inhibited AO activity more potently than XO, which was more evident with non-planner flavanols. A planner structure seems to be essential for a potent inhibitory effect and any substitution by sugar moieties reduces the inhibitory effects. This study could provide a new insight into AO natural inhibitors with potential to lead to some food-drug interactions.

Synthesis and hydrolytic behavior of ibuprofen prodrugs and their PEGylated derivatives.

Polyethylene glycol (PEG) derivatives of ibuprofen were prepared by esterification of PEG monosuccinate with hydroxy ethyl ester (HEE), hydroxy ethylamide (HEA), and hydroxy ethyl thioester (HET) of ibuprofen. Hydrolysis of HEE-PEG, HEA-PEG, and HET-PEG were studied in vitro with or without esterases to investigate the applicability of these PEGylated prodrugs. The polymeric prodrugs released major fraction of the parent drug (ibuprofen) and a small fraction of hydroxy ethyl derivatives after 48 hr. In HET-PEG, the amount of drug release was higher than HEE-PEG and HEA-PEG. The difference between acidic and alkali buffered solutions was considerable. In human plasma, 50% of drug was released after 150 hr incubation at 37 degrees C from HET-PEG.

Influence of poly(ethylene glycol)-alpha-cyclodextrin complexes on stabilization and transdermal permeation of ascorbic acid.

The present study was conducted to investigate the effect of poly(ethylene glycol)-alpha-cyclodextrin (alpha-CD) complexes on stabilization and cutaneous permeation of ascorbic acid from specially prepared transdermal patches. Poly(ethylene glycol) citrate (6-armPEG) and its inclusion complex with alpha-CD were prepared and used for preparation of the transdermal patches. Duro-Tak 87-2979 was taken as an adhesive matrix in combination with ascorbic acid. A diffusion cell with an artificial membrane was used to evaluate the absorption of ascorbic acid from the patches. The influence of drug release of alpha-CD and two types of its PEG complexes (as the novel permeation enhancers) was tested. The 6-armPEG-alpha-CD complex consisting of a PEG-citric acid ester at a concentration of 0.08-0.1% (w/v) is a suitable stabilizer for ascorbic acid during UV assay. The release studies showed that the type of enhancer is important in diffusion of the drug across membrane. Furthermore, the diffusion of ascorbic acid was considerably enhanced in the presence of 6-armPEG-alpha-CD complex. Inclusion complexes of 6-armPEG with alpha-CD at a concentration of 0.08-0.1% (w/v) is a suitable stabilizer for UV method of assay. The present data suggest that 6-armPEG-alpha-CD complex is also useful in enhancing the release of ascorbic acid from the acrylic type pressure sensitive adhesives.

Evaluation of in vitro-in vivo correlation and anticonvulsive effect of carbamazepine after cogrinding with microcrystalline cellulose.

PURPOSE: Carbamazepine is a poor water soluble drug and its bioavailability is limited by dissolution rate. Dissolution, serum concentration and anticonvulsive effect of the drug have been evaluated after cogrinding with microcrystalline cellulose. A cogrinding technique was used to increase the dissolution, serum concentrations and anticonvulsive effect of the drug. A novel deconvolution technique of in vitro in vivo correlation was evaluated. METHODS: The drug coground with microcrystalline cellulose, the corresponding physical mixture, unground and ground drug powder were subjected to dissolution measurement. Coground and unground drug serum concentrations were investigated in rabbits. Also the anticonvulsive effects of the latter preparations were assessed in mice. For elucidation of observed in vitro and in vivo differences FT-IR spectroscopy, X-ray diffraction patterns and DSC thermograms of the preparations were studied. RESULTS: The dissolution of the coground was the highest (percent dissolved in the first 20 minutes, %D20', was 97.5). The unground drug powder exhibited the lowest dissolution (%D20'=40). The difference was reflected in their corresponding area under the mean serum concentration curves between 0-16 hr (118.96 vs 54.17 microg x hr/ml) as well as protection abilities against strychnine and electrically induced seizures. The onset of tonic seizures induced by strychnine was increased between 40-140% in the case of the coground system depending on dose and time of carbamazepine administration. CONCLUSION: Cogrinding was an effective technique in increasing carbamazepine dissolution due to reduced crystallinity as seen in X-ray pattern, enhanced wettability and decreased particle size, which in turn resulted in increased serum concentrations and its anticonvulsive effect. A novel simple deconvolusion technique not requiring intravenous data denoted as the double reciprocal area method was used to establish correlation between in vitro and in vivo parameters.