Iraqi Journal of Pharmaceutical Sciences
Iraqi Journal of Pharmaceutical Sciences (IJPS) is the official journal of the College of Pharmacy, University of Baghdad. The IJPS is a biannual specialized scientific journal which was first founded in 1979. The aim of this journal is to support scientific knowledge and encourage scientific research and publications. The IJPS provides a forum for reporting innovations, production methods, technologies, initiatives and the application of scientific knowledge to all aspects of pharmaceutical sciences, including advanced drug delivery systems, drug targeting, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and pharmacy practice . The journal has issued thirty volumes and fifty three issues from 1979 until December of 2021. Iraqi Journal of Pharmaceutical Sciences (IJPS) is an open access peer-reviewed journal. Open access (OA) refers to a free and unrestricted online access to journal articles. The OA content is open to all with no access fees. For more information on Creative Commons license and the benefits of publishing an open access article
University of Baghdad- College of Pharmacy
Synthesis, Characterization and Antimicrobial Evaluation of New Compounds Derived from 2-Mercaptobenzoxazole
The synthesis of a novel series of 2-mercaptobenzoxazole hydrazide(2-benzo[d]oxazol-2-ylthio) acetohydrazide) derivatives (3a-c, 4a, and 4b) through the use of various sulfonyl chlorides in dichloromethane and triethyl amine for the compounds (3a-c) and different aromatic aldehydes in the presence of glacial acetic acid for the compounds (4a, b). The novel compounds' anti-microbial effectiveness has been evaluated in vitro against two of (G+Ve) and two of (G-Ve) bacteria and for fungal activity. In comparison to other compounds, compounds (3a and 3b) had the most anti-microbial action against Candida albicans and pseudomonas aeruginosa, respectively, while compound (3c) was more effective against gram-positive bacteria (Streptococcus pyogenes) compare with other compounds. By using their ((melting point, Thin Layer Chromato-graphy , attenuated total reflectance-Fourier transform infrared (ATR-FTIR), and 1 HNMR, the target compounds were identified.
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Spanlastics for Targeted CNS Drug Delivery
Numerous pharmacological compounds now on the market are ineffective in treating brain disorders ,they are not getting to the brain with the concentration required to have a pharmacological effect. Since there are many barrier as blood brain barrier (BBB), P-glycoprotein (an active efflux transporter), and specific enzymatic activity are some of the mechanisms that protect the brain from harmful circumstances. These systems, in particular BBB hinder therapeutic interventions of many medications . Thus, the majority of the medicine cannot give the desired effect because they cannot penetrate the brain, so they are useless in the treatment of brain illnesses . As a result, numerous Therefore, strategies that could enhance drug delivery to the brain. Thus, the vesicular medication delivery devices have made important advancements in nanotechnology. These systems are useful for avoiding a number of problems with traditional dosage forms, liposomes, nanoparticles and spanlastic are proving to be more effective. Spanlastics are surfactant-based elastic vesicular drug delivery method that traps the medication in the core cavity as a bilayer, they are amphiphilic in nature and deliver both hydrophilic and hydrophobic medications . Surface active agent , edge activator and ethanol are used to prepare the spanlastic and many methods can be used to prepare of these vesicles .
A Comprehensive Pharmacognostic, Phytochemical Description, and Clinical Implementation of Amaranthus viridis
The pigweed family, Amaranthaceae, includes Amaranthus viridis, popularly known as green amaranth. This herb grows quickly and has an annual lifespan. Traditionally, it has been used to treat anemia, eczema, bronchitis, inflammation, and leprosy. Additionally for respiratory issues, ocular conditions, and asthma. The phytochemical analysis of Amaranthus viridis L extracts identifies the presence of several categories of biologically active substances (phytochemicals): phenolics, which include flavonoids, tannins, and phenolic acids. Alkaloids, cardiac glycosides, various classes of triterpenoids, and steroids were also found. Numerous investigations on A. viridis have been conducted to explore its pharmacological range. The majority of research identified laxative, hepatoprotective, analgesic, anti-inflammatory, antitumor, antimicrobial, anti-diabetic, antitumor, wound healing, and antioxidant properties. The goal of the current review of the literature is to give extensive information on the morphological traits, folk usage, phytochemicals, and pharmacological properties of Amaranthus viridis.
Design, Molecular Docking, Synthesis and Antiproliferative Evaluation of New 5-Aminoisatin Derivatives
Two series of compounds derived from 5-aminoisatin were synthesized, Schiff bases IIa-c and ureido derivatives of 5-aminoisatin Schiff bases IIIa-c& IVa-c.The proposed compounds were successfully synthesized and purified; they were characterized and identified using: melting point, IR spectroscopy, 1H-NMR and13C-NMR; The in vitro cytotoxic activity of these novel compounds was tested and molecular docking-based in silico tyrosine kinase selectivity via GOLD Suite (v.5.7.1); Our docking results and the experimental data (In vitro study) are in good accord since the compound IIIa shows the highest docking result and at the same time showing a promising cytotoxic activity among the tested compounds when tested against (A549) cancer cell lines by the MTT assay in comparison with erlotinib. Additionally, ADME studies were conducted to determine which of them are candidates for oral administration, as well as their absorption location, bioavailability, topological polar surface area, and drug-likeness.
5-Aminoisatin, ADME, Docking, GOLD, Lipinski rule
Preparation and Characterization of Isradipine as Surfactant Free Emulsion
Isradipine is a calcium channel blocker, it’s the drug of choice for oral therapy of severe hypertension and urgent hypertension crises in pediatrics. It belongs to the BCS class II. Its oral bioavailability will be approximately 15 to 24 %. This study aims to prepare a stable, low-toxic, eco-friendly, surfactant-free oral oil-in-water emulsion of Isradipine for pediatric patients and enhance dosing accuracy. Isradipine surfactants–free emulsions (SFE) were prepared to protect this ester drug from hydrolysis, oxidation, photosensitivity, increasing its solubility and absorption, thereby improving its bioavailability. The study used corn and grape oil to prepare SFE for solubilizing Isradipine. The SFE was stabilized by different percentages of β-cyclodextrin to encapsulate oil droplets. Twelve formulas were prepared using a homogenizer and mixed for 5 minutes at 10,000 rpm and 25ºC. The SFE formulas were evaluated for organoleptic attributes, thermodynamic stability, dilution test, viscosity, pH, drug content, droplet size distribution, and in-vitro dissolution. Among all the prepared SFE formulas, F3 containing 8g of β-CD and 15g of Corn oil, was chosen as the optimum SFE formula due to its small particle size range1451±0.01 nm, respectable pH, good organoleptic attributes, excellent thermodynamic stability, acceptable viscosity (1869.5±1.54), acceptable drug content percentage, and highest dissolution rate. F3 was further tested for drug excipient compatibility using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM), showing complexation between the drug and oil droplets, and spherical droplets of Corn oil surrounded by β-CD.
Determining the level of miRNA 133a-5p and Mid Regional pro-Adrenomedullin in Patients with Stable Angina Pectoris
Chronic stable angina pectoris (CSAP) is a prevalent heart disease which can be defined as a symptom or a clinical syndrome of stable coronary artery disease (CAD). CAD is usually caused by the presence of atherosclerotic plaques or blood clot within coronary arteries that may lead to ischemia. miRNA 133a is mainly expressed in the muscle and it has a role in apoptosis, angiogenesis, hypertrophy, atherosclerosis and ischemia. MR-proADM is of endothelial origin and produced by different sites in the body mainly by the heart, kidneys, lungs and adrenal medulla. MR-proADM plasma level is thought to be predictive of CAD. The aim of the current study was to detect the serum levels of microRNA 133a-5p and MR-proADM in a sample of Iraqi patients with chronic stable angina and obstructive CAD with normal LV ejection fraction so that to investigate whether these biomarkers can be used to diagnose those patients. In this case-control study, fasting venous blood samples were collected from 90 male and female subjects (40-76 years old) who were presented to the outpatient clinic as having chest pain. An electrocardiography, echocardiography and conventional coronary angiography were applied by the cardiologist for all the participants. Routine biochemical tests and patients questionnaire were also applied. Left ventricular ejection fraction was detected using the biplane M mode method. Accordingly, the patients who showed evidence of atherosclerotic plaque and CAD on the angiography were classified as angina patients (n=60) and those who showed no evidence of coronary obstruction and ischemia on the angiography (normal angiography) were classified as being a control group (n=30). The fold of gene expression of miRNA 133a-5p in serum and serum levels of MR-proADM, fasting blood glucose (FBG), urea, creatinine, TGs, total cholesterol, LDL-C, HDL-C and VLDL-C were measured. Results: the fold of miRNA 133a-5p gene expression in serum and the serum levels of MR-proADM were significantly higher in patients (P≤ 0.01) and ROC curve showed that miRNA 133a-5p had 98% sensitivity and 47% specificity with AUC=0.8, whereas, MR-proADM had 100% sensitivity and 100% specificity with AUC=1.0. So, it can be concluded that MR-proADM could be used as an independent biomarker for the diagnosis of stable angina patients with normal LV ejection fraction, whereas microRNA 133a-5p is better to be used in combination with other biomarkers to give more accurate diagnosis.
Preparation and Evaluation of Oral Capsule-Based Niosomes for the Anti- Cancer Drug Axitinib
Niosomes are bilayer vesicles formed by the self-assembly of non-ionic surfactants, they are receiving increasing attention as a potential oral drug delivery system specifically for poor soluble drugs to enhance its dissolution and ultimately its absorption and oral bioavailability. Axitinib is a tyrosine kinase inhibitor works by blocking the vascular endothelial growth factor receptors (VEGFR), decreasing the development of neovascularization which supress the tumour growth. It is classified as class 11 drug which has low bioavailability due to its poor solubility and absorption. In this study, axitinib (AXT) capsules based niosomes formulated by thin film hydration method as liquid niosomal dispersion using (span 60: cholesterol (1:1 weight ratio), 5mg dicetyl phosphate (DCP) and 5mg drug, with entrapment efficiency 96.5% and particle size 64.5nm), then converted to dry powder via silicified microcrystalline cellulose (SMCC) and evaluated for flow properties, in-vitro drug release, drug-excipients compatibility study, permeation study, cytotoxicity study and bioavailability investigation. The results showed good flow properties of the powder content of prepared capsules based niosomes where the angle of repose was (32.3± 1.1), Carr’s index was (12±0.58) and Hausner ratio was (1.12±0.01). The drug release from capsules based niosomes was rapid in initial phase where 40.61% of drug released from capsules based niosomes in acidic medium (stomach) followed by continuous release (in intestine) where 100% of drug released within 4 hours, while the drug released completely(100% of drug released within 20 minutes ) in acidic medium (stomach) from conventional marketed tablets, the results of FTIR and DSC revealed the purity of drug and incorporation of it in amorphous form and no interaction between drug and excipients. The permeation results revealed that the encapsulation of drug in vesicles enhanced the drug intestinal permeation in comparison to marketed tablets, where the permeation percent of the powder content of capsule based niosmes was 78% while the permeation percent of the marketed tablets was 58%. The study of in-vitro cytotoxicity effect showed that the cytotoxic effect of prepared capsule based niosomes significantly (p<0.05) higher than pure drug and it is increased with time, where the IC50 value for the pure drug and capsule-based niosomes were found to be 120 µg/ml and 80.26 µg/ml respectively. Bioavailability investigation of capsules based niosomes compared with marketed tablets was revealed that capsules based niosomes enhanced the oral bioavailability of axitinib comparison with the marketed tablets, the pharmacokinetic results showed that the capsules base niosomes have been revealed higher peak drug concentration ( Cmax = 5.23±0.07µg/ml) with maximum peak time (Tmax =4hr) while the Cmax= 4.8±0.025µg/ml and Tmax = 6 hr for conventional marketed tablets , AUC 0-∞ for capsule based niosomes was (70.092µg/ml.hr) is highly significant (p<0.05) comparison with AUC 0-∞ for marketed tablets which was( 53.714 µg/ml.hr), this substantial difference suggests an improvement in drug solubility, dissolution, and absorption, eventually leading to an improve in oral bioavailability when drug loaded in nano-carrier (niosomes). The results of this study was indicated that niosomes exhibit potential as nano-carriers for enhancing the cytotoxic effects of anti-cancer drug, permeability and improving their oral bioavailability.
Effect of Different Type of Terpenes on Disulfiram Loaded Transdermal Invasomes Preparation and in-vitro Characterization
Disulfiram (DSF) is a thiocarbamate derivative that has been used for the treatment of alcoholism. Researchers recently found out that DSF, a medicine authorized by the FDA to prevent alcohol consumption, has been investigated for its potential in cancer treatment. DSF, when taken by mouth, undergoes extensive metabolism in the liver, making it unsuitable for cancer treatment via oral administration. Furthermore, DSF has demonstrated the ability to enhance the cytotoxic impact of anticancer medications while preserving healthy cells. To solve the problem of instability and insufficient therapeutic efficacy, invasomal vesicles developed with better entrapment efficiency and size to serve as a carrier for the transdermal delivery of disulfiram, The lipid vesicular carrier is used to evaluate the effects of different formulation variables, such as type and concentration of terpenes, on vesicle size, polydispersity index (PDI), and entrapment efficiency (EE). Nine invasome formulations were developed using the thin film hydration process. The optimized formula was further analyzed for its zeta potential, morphology, and in vitro release research to improve the DSF-IV8 formula. The DSF-IV8 invasome, which is composed of DSF, soya phosphatidylcholine (2%), carvacrol (1% w/v), and ethanol (40% v/v), demonstrated optimal characteristics, including spherical vesicles having a particle size of 119.2±2.2 nm, a PDI of 0.18±0.05, and an EE of 95.3±0.8%. The zeta potential value was measured to be -33.6±1.6 mV. The release pattern of DSF-IV8 showed an initial rapid release followed by a continuous release over 24 hours, in contrast to pure DSF which only had a release rate of 16%. Eventually, the thin film hydration approach was shown to be effective in formulating invasomal dispersion.
Cancer, Disulfiram, Transdermal delivery, Invasome, Terpene
Therapeutic Drug Monitoring of Infliximab in Iraqi Patients with Moderate to Severe Ulcerative Colitis
The term "inflammatory bowel disease" refers to a group of gastrointestinal tract inflammatory disorders that are considered idiopathic, chronic, and relapsing. The two primary disorders that comprise inflammatory bowel disease are Crohn's disease and ulcerative colitis. Infliximab, a chimeric monoclonal antibody, is a medication used to treat a number of autoimmune diseases such ulcerative colitis, Crohn’s disease, rheumatoid arthritis, and psoriasis. Therapeutic drug monitoring is a tool used in therapeutic decision-making that allows dosage modifications to be made in accordance with clinical and laboratory measures, usually blood concentrations of the drug, in order to achieve the drug exposure linked to the best response rate. The trough concentrations of infliximab at 3 to 7 μg/mL is most effective at inducing remission in patients with inflammatory bowel disease. The aims of the current study were to determine the achievement of trough level target, development of antidrug antibodies to Infliximab, assess response to therapy and to study trough level relation with different variables in patients with ulcerative colitis. The present study was cross-sectional conducted at ‟Gastroenterology and Hepatology Teaching Hospital/ Medical City / Baghdad / Iraq” during May 2022 to November 2022. Forty candidate patients with ulcerative colitis were included [Males =20 (50%), Females=20 (50%)] with median age [32.00 (28.50-40.75) years]. According to trough level, disease activity and development of antibodies, escalation of the dose were recommended for 10 patients (25%), switching therapy were recommended for 16 patients (40%), and continuation of the same dosage regimen were recommended for 14 patients (35%). In addition, results of current study showed that age, body mass index, and packed cell volume were significantly higher and erythrocyte sedimentation rate was significantly lower in in patients achieved target infliximab trough level compared to those not achieved. By using multivariate binary regression analysis only age and erythrocyte sedimentation rate can be used to predict the achievement of target trough level of infliximab. In conclusion, therapeutic drug monitoring of infliximab to determine the trough level and antidrug antibodies can explain the possible causes of non-responsiveness to this drug among ulcerative colitis patients with subsequent recommendations based on these findings.
Preparation and evaluation of injectable dosage form for Pemetrexed-monoclonal antibody conjugate
Antibody-drug conjugates (ADCs), a powerful type of pharmaceutical medications that combine immunotherapy and chemotherapy. Pemetrexed is a multitarget antifolate agent that inhibit essential enzymes involve in purine and pyrimidine synthesis, therefore serious toxicities of pemetrexed are due to lack of selectivity despite its broad antitumor activity in a wide variety of solid tumors. The aim of the study was to formulate and evaluate our prepared Atezolizumab (AtZ)-pemetrexed (Pem) conjugates as an intravenous (I.V) injectable dosage form. The characterization of the I.V formulation involved drug content, particle size, pyrogen test, sterility test, toxicity test, and stability test. The work revealed that our previously prepared AtZ-Pem conjugate products (both using PEG and gamma amino butyric acid GABA as linkers) showed different retention time by HPLC-UV, the particle size of the I.V dosage form revealed that AtZ-GABA-Pem had smaller size (465nm) and more uniform size distribution (PDI 0.451), while the particle size and PDI for AtZ-PEG-Pem were (1297nm) and (0.9912) respectively. The two prepared I.V preparations for AtZ-PEG-Pem and AtZ-GABA-Pem showed good stability after six months storage at 6 °C, unacceptable stability results when both formulas stored at room temperature. Both I.V preparations for the conjugates were not toxic, sterile, and pyrogen free. The prepared injectable preparation could be used as a potential alternative to the available injectable preparations for Pemetrexed to improve its targeting and selectivity, hence reducing its serious side effects.
Estimation of Quercetin Treatment Effects in Polycystic Ovarian Syndrome (PCOS) Induced Rats
Polycystic ovary syndrome (PCOS), also known as a common polygenic endocrine condition, affects the ovaries and results in infertility and abortion. Dyslipidemia, Diabetes, hypertension, endometrial cancer, and other illnesses may all be made more likely by PCOS. Various drugs are used to treat PCOS, but they have several drawbacks and cannot effectively cure the condition. Therefore, and due to its strong antioxidant activity, anti-obesity, anti-inflammation, and other actions, the flavonoid quercetin has been proven to have health-promoting properties. The purpose of the study was to assess quercetin's impact activity in the treatment of PCOS - induced rats. A PCOS rat model was developed using testosterone. Female albino Wistar rats (170±10 g) were subcutaneously injected with either testosterone propionate (TP) 10 mg/kg/day body weight or propylene glycol (PG) as vehicle 0.5ml daily, for 28 days (induction stage). The PCOS-induced rats were divided into two groups, one was treated orally with the vehicle (PG) and the other was treated orally with quercetin 25mg/kg/day over a period of 35 days (treatment stage). So, the biochemical assays proved the efficacy of quercetin on lipid profile and glucose uptake, in rat treatment with quercetin significantly decreased (P < 0.05) in body weight and fasting blood glucose, fasting insulin, cholesterol and triglyceride levels unlike PCOS-induced rats also, a significant increase in HDL level was achieved in quercetin - treated group compared to PCOS group. Thus, we conclude that quercetin is an effective remedy in modulating metabolic features and treating PCOS.
Biochemical assay, lipid profile, PCOS, Quercetin, Testosterone propionate.
Oral Itraconazole and Terbinafine vs. Itraconazole as a Novel Regimen for the Newly Emergent Chronic Tinea: A Comparative Clinical Study
Dermatophytosis is the most common contagious fungal disease. Iraq, like the other many countries around the world, is facing an emergence of chronic, resistant and relapsing tinea infections. This study compared the efficacy, safety and the relapse rate of a combination therapeutic regimen of itraconazole and terbinafine vs. itraconazole alone in the treatment of chronic tinea infections. The research was conducted at the dermatology and venereology outpatient’s unit, Ramadi Teaching Hospital, Iraq, during the period from May 2022 to May 2023. Patients were divided equally into two groups. Group I received combination of itraconazole and terbinafine while group II was on itraconazole alone for eight weeks for each group. For assessment of relapse rate, follow-up was for two months. Only 148 out of 160 of enrolled patients completed the study. 98 (66.2 %) were males and 50 (33.8%) were females. The mean of the age (±SD) of the total was 33.04±12.65. There was no significant difference in their residency. Family history was positive in majority of patients 119 (80.4%). After two weeks, there was significant difference in response to treatment, where a marked clearance was achieved by 54 (73%) patients in group I, while only 17 (23%) patients in group II, (p value 0.00). After 8 weeks, complete clearance was 68 (92%) in group I, while 35 (47%) in group II (p value 0.00). Marked clearance was 6 (8%) in group I, while 33 (45%) in group II (p value 0.00). Relapse rate, after 16 weeks, was 5 (7%) in group I, while 42(57%) in group II (p value 0.00). We concluded that therapeutic regimen of itraconazole and terbinafine were effective, safe and well tolerated with low relapse rate.
Antifungal, Chronic dermatophytosis, Itraconazole, Terbinafine.
Preparation and Evaluation of Pimecrolimus Nanoemulsion for Topical Delivery
One of the innovative approaches to delivering drugs via topical route is nanoemulation (NE), which is easy to manufacture, stable over the long term, and has a potent solubilization property. Pimecrolimus is a low water soluble drug used to treat psoriasis, eczema, atopic dermatitis and vitiligo. This work describes the high-energy ultrasonication technique used to prepare pimecrolimus nanoemulsion. A pseudo-ternary phase diagram was created in order to determine the ideal ratios of oil-surfactant/co-surfactant mixture for the creation of nanoemulsions. Based on pimecrolimus's solubility in various oils, surfactants, and co-surfactants, Tween 80 was chosen as a surfactant, ethanol as a co-surfactant, and benzyl alcohol as an oil phase .The work involved creating twelve NE formulas for optimization, and evaluated for thier droplet size, visual transparency, entrapment efficiency, zeta potential, physical stability, and in vitro release. Droplet size is 45.1 nm, entrapment efficiency is 92.59%, PDI is 0.402, Zeta potential is -0.8 mV, were displayed by the ideal NE formula, which released 76.3% in 5h and 96.6% of pimecrolimus in 24h compared with the commercial cream which released 26.2% in 5h and 42.5% of the drug in 24h. This suggests that the prepared formula has promising potential as an effective nanocarrier to enhance drug solubility and permeability and, consequently, its therapeutic effectiveness topically through the skin. These results demonstrated the formula's promising potential as an effective nanocarrier to improve drug solubility and permeability and, consequently, its therapeutic effectiveness topically through the skin.
nanoemulsion, pimecrolimus , benzyl alcohol , tween80, RP-HPLC.
Study of ATP/GTP binding protein -1 (AGTPBP-1) in Fibrotic Lung Disease with and without COVID-19 Vaccination
Background : It took less than two months for the severe acute respiratory syndrome that caused by coronavirus disease 2019 to become a palsoemic . ATP/GTP binding protein 1 (AGTPBP1) is responsible for encoding a number of proteins, including cytosolic carboxypeptidase1 (CCP1), which has been investigated in degenerative diseases also has a role in the regulation of polyglutamylation of tubulin. Patients and methods : A 150 people participated in this study were split into three groups, The first group (G1), served as control group included (50) subjects . Second group (G2) consisted of (50) Fibrotic Lung Disease (FLD) patients without COVD-19 vaccine . Third group (G3) consisted of (50) FLD patients with COVID-19 vaccine . ESR , CRP,LDH, Ferritin ,D-dimer. were measured by enzymatic method . AGTPBP1 levels were measured using the ELISA technique . Results : Result show highly significant increases in ESR, CRP and LDH levels among three groups . ANOVA descriptive analysis of Ferritin, D-dimers and AGTPBP1 for all studied groups . Show a significant increase in levels of G3 and G2 comparing to G1 . In addition a significant increase found in G3 comparing to G2 . Conclusion : The present study submits novelty in COVID-19 fields by Focus on role of new parameter such as AGTPBP1 in corona-19 vaccine (Pfizer) that used in Iraq .
Preparation and Evaluation of Dapagliflozin Propanediol Monohydrate-Loaded Transferosomal Dispersion for Transdermal Delivery
The transdermal route of drug delivery has received significant attention in pharmaceutical research due to its ability to overcome many challenges associated with oral medication administration, including the ability to bypass first-pass metabolism, ensuring a more predictable and prolonged period of action, as well as minimizing the occurrence of adverse reactions. Transferosomes are a type of ultra-deformable lipid-based vesicles, that have the potential to offer several benefits compared to the traditional lipid-based vesicles such as liposome. The major goal of this research was to prepare (for the first time) dapagliflozin-loaded transferosomes for the purpose of minimizing the potential risk of hyperglycemia associated with oral administration for the treatment of diabetes. The transferosomes were prepared by the thin film hydration method with 5 mg of drug and different proportions of phospholipid and edge activators. The transferosomes were characterized for entrapment efficiency (EE), drug content, pH, vesicle size, PDI, zeta potential,viscosity, in vitro drug release, ex vivo permeation, FTIR and SEM. Tween 80-based transferosomes (F6) at a 95:5% w/w phospholipid:edge activator ratio yielded the highest EE (93±0.77%), drug content (99.7±1.68%), in vitro drug release within 24 hours (99±1.4%), vesicle size (105.8±1.61nm), PDI (0.436±0.01), viscosity (155±1.95 cP), and zeta potential (-35.15mV), which was selected as the optimum formula. The formula had good ex vivo permeation after 24 hours (289.8±5.2 µg/cm2, 91% drug permeated), compatible drug-excipients according to FTIR, and nano-sized spherical shape vesicles according to SEM. Three months of stability testing according to the ICH guidelines revealed that the formula was stable at 4±2C° and 25±2C°. As a conclusion, this research suggested that transferosomes can be prepared as a transdermal drug delivery system with suitable properties to be given once daily as transdermal patch for the antidiabetic drug dapagliflozin.
Improvement of Solubility and Dissolution of Niclosamide using Metal Organic Framework 5 (MOF-5)
Metal-organic frameworks-5 (MOF-5) were explored for enhancement of the solubility and dissolution of the drug niclosamide (NIC). MOF-5 was synthesized by solvothermal method and NIC was loaded into it (NIC@MOF-5). Characterization was done using field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller surface area (BET-SA), and energy-dispersive X-ray spectroscopy (EDS). The effect of loading time on the percentages of entrapment efficiency (%EE) and loading capacity (%LC) were studied. The effect of incorporation into MOF-5 on saturated solubility and dissolution profiles of NIC was investigated in three different media: acidic buffer solution (ABS) pH 1.2, deionized water (DW) pH 6.2, and phosphate buffer solution (PBS) pH 7.4. The results showed that the solubility of NIC was significantly improved upon incorporation into MOF-5 in all media. In ABS pH 1.2, it was improved by 3.4 times (10.63 ± 1.04 µg/ml versus 3.17 ± 0.55 µg/ml). In DW pH 6.2, it was improved by 4.7 times (60.37 ± 4.74 µg/ml versus 12.83 ± 1.76 µg/ml). The biggest improvement was in PBS pH 7.4 by 6.1 times (209.85 ± 9.77 µg/ml versus 34.5 ± 1.66 µg/ml. For dissolution, the cumulative release at the end of point was significantly higher for NIC@MOF-5 in all three media: 51.20% ± 6.52% versus 10.77% ± 1.78% in ABS pH 1.2, 54.09% ± 1.81% versus 12.44% ± 0.57% in DW pH 6.2, and 84.87% ± 9.99% versus 19.48% ± 1.82% in PBS pH 7.4. Characterization confirmed the identity of NIC and MOF-5 as well as loading of NIC into MOF-5 without significant interactions. It is, therefore, concluded that MOF-5 is a feasible formulation approach to improve the solubility of and dissolution of NIC in either acidic media, water, or basic media.
Assessment of Fibroblast Growth Factor- 23 and Klotho Protein in Children with Steroid-Sensitive Nephrotic Syndrome and Steroid-Resistance Nephrotic Syndrome
Idiopathic nephrotic syndrome is a common disease that affects children’s kidneys and occurs due to a specific defect in the glomeruli, which leads to the leakage of protein into urine in large quantities. Fibroblast growth factor-23 (FGF-23), produced by bone, is essential for controlling the metabolism of 1,25-dihydroxy vitamin D and phosphate, but it also requires the Klotho co-receptor to perform its function. Therefore, the purpose of this study was to evaluate whether FGF-23 can be used as a biomarker to determine the likelihood of recurrent relapse as well as to differentiate between steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) treated with glucocorticosteroids. In this cross-sectional study, 85 patients with idiopathic nephrotic syndrome were divided into four groups: Out of 50 children included in this study with (SSNS) were grouped in the first group (20) in relapse and the second (30) in remission, in addition to 35 child had (SRNS) were divided as: the third group of (20) in the relapse phase and the fourth group of (15) in the remission phase, while the control group included 40 healthy children. The fibroblast growth factor (FGF-23) levels and its co-receptor Klotho were measured in these patients using an ELISA kit. Our results revealed that serum levels of FGF-23 were significantly elevated in steroid-sensitive NS with a mean of (51.73 ng/L) in relapse and (16.49 ng/L) in remission, while for the steroid-resistant groups (67.25 ng/L) in relapse and (24.66 ng/L) in remission, compared with the control group with a mean of 7.73 ng/L (P < 0.0001). At the same time, Klotho concentrations were decreased for all patient groups compared with the control group. Hence, FGF-23 serum level is a potential biomarker to identify patients with frequent relapses at a cutoff value (16.055 ng/L). While its ability to distinguish between SSNS and SRNS patients was lower at a cut-off value of (20.00 ng/L).
Formulation And Evaluation of Lipo-Nanosphere Loaded Docetaxel Drug
As nanotechnology advances, the nanoliposphere is being considered as a possible drug carrier to enhance the bioavailability of some lipophilic drugs. Lipospheres are often employed to deliver hydrophobic agents because lipids can make pharmaceuticals more soluble and release them in a controlled manner. Antineoplastic medication docetaxel (DCX) is useful for treating a variety of complicated malignancies, particularly cancers of the breast and ovary. Because it is highly hydrophobic, low bioavailability due to the extreme toxicity of DCX, it was only developed for intravenous infusion on the market at a dose of 100 mg/m every three weeks (Taxotere®). The creation of lipo-nanospheres (LPNS) as docetaxel carriers is discussed in this work. The synthesized lipo-nanospheres, which are made of biodegradable and bio-acceptable lipids, are described for surface morphology, crystallinity, and release studies. This accomplished by Fourier transform infrared spectroscopy (FTIR), polydispersity index, particle size, and in vitro release studies Due to delayed drug diffusion from lipo-nanospheres, docetaxel's in vitro release behaviors from the created lipo-nanospheres showed a biphasic pattern, with a quick initial release and a slower, continuous release over the course of 24 hours. Our findings show that the created formulation of lipo-nanospheres containing docetaxel can be effective against complicated malignancies.
Patients’ Knowledge about Safe Measures Post Implantable Cardioverter Defibrillator
Patients who have implantable cardioverter defibrillators (ICD) are challenged with multiple physical, psychological, and social complications. It is important to understand ICD patients’ knowledge about safe measures post-implementation. The study aims to assess patient’s knowledge of the safe measures after implantable cardioverter defibrillator. A descriptive-analytical study was carried out from October 19th, 2022 to January 16th, 2024 to determine the patient’s knowledge about safe measures after ICD. Non-probability (purposive) sample of 70 Patients with an ICD during routine checking and programming the device in outpatient at Ibn – Al-Bitar specialized center in Baghdad city. The study instrument was composed of three parts, socio-demographic characteristics, medical information, and patient’s knowledge of the safe measures after ICD implantation. Data were analyzed through the application of descriptive and inferential data analysis approaches by using SPSS version 26. The results of the study show majority of the sample was male, married, and aged (42- less than 54) years and the maximum age of patients who attended to study was 76 years, they did complete the primary educational level, and a high percent were unemployed. also, most of the sample was median income, and their duration of implantation is 5 years & above. The maximum duration of implantation of patients who attend the cardiac center is 14 years. The majority of patients were not smokers. Patients' knowledge of safe measures post-ICD was fair to the level regarding safe activity and electrical devices. and the poor level of magnetic devices and medical devices. There is a significant association among the patients’ knowledge with sex and education level variables at P ≤ 0.05. Conclusion: The knowledge of patients regarding safe measures post-ICD was poor level as general. Post-intervention education should be especially important to patients to avoid unnecessary limitations.
Implantable cardioverter defibrillators, Knowledge, Safe measures
Ophthalmic Single and Mixed Polymeric Nanomicelles using Brimonidine as a model drug: Preparation, Characterization, and Physical Properties Evaluation
Nanomicelles, a nanocarrier drug system, recently applied in medical research as a technique to deliver therapies to the targeted site. Normal nanomicelles building units are amphiphilic molecules (surfactants or polymers) containing hydrophobic tails and hydrophilic heads that self-assembled into the hydrophobic core-hydrophilic shell-like structure that dispersed into the aqueous media upon hydration. Polymeric nanomicelles had a lower critical micelle concentration by thousands of folds than surfactants of low molecular weight, resulting in a higher stability and circulation time after administration. Mixed nanomicelles have an extra advantage by improving the stability and encapsulation efficiency compared to single ones. Soluplus, an amphiphilic grafted copolymer used to enhance the solubility of the hydrophobic drug, and tocophersolan, a biocompatible and biodegradable vitamin E derivative polymer used as a stabilizer and permeability enhancer, were studied; both of them had hydrophobic and hydrophilic chains that are self-assembled into normal nanomicelles upon contact with aqueous media. This study aimed to prepare single soluplus and mixed soluplus-tocophersolan polymeric nanomicelles and compare their physical properties using a hydrophobic drug (brimonidine) as a model. The results showed that soluplus increases brimonidine solubility proportionally as its concentration increases. Soluplus concentration of 59mg/ml had the highest molar solubilization capacity (3.715) and the fraction of brimonidine encapsulated (0.872) with a negative value for Gibbes standard-free (-3.453), indicating a spontaneous nanomicelles formation. The physical appearance and the percentage of entrapment efficiency of the single soluplus nanomicelles were significantly affected by brimonidine concentration, while the particle size and the polydispersity index were not affected. The best single soluplus-brimonidine-loaded nanomicelles were transparent with particle size (75.75±1.13nm), polydispersity index (0.1243±0.02), and percentage of entrapment efficiency (53.49±0.58), was selected to prepare the mixed one. Variables including tocophersolan concentrations, the temperature of the hydration phase, and the tocophersolan addition phase, were studied regarding their effects on the physical properties of the mixed polymeric nanomicelles in which all of them affect highly significantly the particle size and the percentage of entrapment efficiency but, with no effect on the physical appearance and polydispersity index. The best mixed polymeric brimonidine-loaded nanomicelles were transparent, with tocophersolan added in the organic phase, and had a particle size of (79.55±0.24nm), polydispersity index (0.1222±0.00) and percentage of entrapment efficiency (62.18±0.23), with lowercritical micelle concentration of (3.467*10-7M). The mixed polymeric nanomicelle was more stable than the single one after storage at (4.0±2.0°C) for 90 days and had a faster in vitro release profile and a higher percentage of drug accumulated amount of (78.4±0.28%) within 15 minutes. The FTIR spectra for the individual components and the best-selected mixed nanomicelles indicated their compatibility, while the FESEM results showed a spherical morphology for the mixed polymeric nanomicelles with particle sizes close to that detected by Malvern Zetasizer. In conclusion, soluplus and tocophersolan could be used successfully to prepare spherical and transparent mixed polymeric nanomicelles incorporating a hydrophobic drug in their core with the desired physical properties with higher in vitro release amount and stability compared to single nanomicelles.
Disulfiram Loaded Transdermal Nanoinvasomal Gel Using Carvacrol as Penetration Enhancer
Disulfiram (DSF), an FDA-approved pharmaceutical for the management of alcoholism, has demonstrated its efficacy against several kinds of cancer. DSF has limited solubility, fast metabolism, short duration of action, and instability in physiological environments, mostly caused by rapid degradation in the acidic gastric environment, Therefore, a transdermal gel containing disulfiram, which was loaded into invasomes, was developed to improve the stability of DSF and enable its effective distribution to tumor tissues. The optimal invasomal dispersion was developed in the laboratory using a 4:1 ratio of soya-phosphatidylcholine (SPC) to disulfiram, and 1% carvacrol as a penetration enhancer. Furthermore, three invasomal gel formulas (IV-g1, IV-g2, and IV-g3) have been developed using hyaluronic acid (HA) as the gelling agent at concentrations of 2%, 2.5%, and 3%. These formulations are subjected to further in-vitro evaluation to assess their physical appearance, homogeneity, viscosity, spreadability, and in-vitro drug release. Results indicated that the formula (IV-g3) exhibited better homogeneity, consistency, spreadability, and stability and showed a non-Newtonian flow and a drug content (99.6±0.4%). Compared to the DSF-suspension (16%), the IV-g3 showed a much greater release of DSF (90.03%). The ex-vivo skin permeation of rat abdomen skin for IV-g3 was significantly higher (14.72cm2/h ×10-3) than DSF-suspension's (3.44 cm2/h ×10-3) during an entire day. The enhancement ratio (ER) of IV-g3, which measured 4.27, surpassed that of the DSF suspension. The stability study indicated that there were no significant alterations in the characteristics of the formulation. The study successfully formulated a new transdermal gel by utilizing invasomal nanocarriers. This gel successfully promoted the delivery of DSF through the skin. The transdermal delivery approach exhibited improved stability of DSF, better skin permeability, and enhanced the efficacy of disulfiram.
Nanotechnology, Transdermal delivery, Invasome, Disulfiram, Hyaluronic acid
The Possible Hepatoprotective Effects of Azilsartan against Carbon Tetrachloride CCl4 - Induced Liver Fibrosis in Male Rats in Comparison with Silymarin: ''in vivo Study''
Hepatic fibrosis is a pathophysiological outcome of sustained wound healing response to chronic liver injury charecterized by excessive accumulation of extracellular matrix proteins. Progressive liver fibrosis can be caused by chronic infection of hepatitis B or C, alcohol abuse, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and other relatively conditions. Liver fibrosis, the subsequent cirrhosis represent a serious medical burden; yet, there is still a lack of approved methods or drugs to prevent or reverse liver fibrosis. Therefore, effective hepatic antifibrotic drugs are urgently needed. Aim of this study was to investigate the possible potential hepatoprotective effects of azilsartan in rats against carbon tetrachloride (CCl4)-induced liver fibrosis. Methods: Forty white male albino rats were utilized in this study. During such study liver fibrosis was induced by intraperitoneal (I.P) injection of CCl4 50% in olive oil 1ml/kg twice weekly for 6 consecutive weeks in. Azilsartan and silymarin were administered orally daily concurrently with I.P CCl4 in the treatment groups. Following the end of sixth week from induction and treatment period, all animals were weighed individually, then euthanised and their livers have been weighed to determine the relative liver weight percentage. Furthermore, a piece of each rat liver tissue was homogenized for determination of tissue malondialdehyde and reduced glutathione. Moreover, liver tissues slices were prepared to study necroinflammation degree, and collagen deposition (fibrosis stage) histopathologicaly. Ultimately, transforming growth factor TGF-β1, alpha smooth muscle actin, and hydroxyproline were all assessed for their immunohistochemistry expression levels in this study. The results revealed that intraperitoneal injection of CCl4 in olive oil in rats resulted in inflammation and fibrosis induction and so, increasing in relative liver weight. Such intraperitoneal injection leaded to increased tissue level of MDA, decreased GSH, and elevation in immunohistochemical expression of TGFβ1, alpha smooth muscle actin , and hydroxyproline as compared to normal control group. Finally, Oral administration of azilsartan and silymarin was significantly improved discussed parameters representing hepatoprotection.
Liver fibrosis, Azilsartan, CCl4, Collagen, Silymarin
Hepatoprotective effect of azilsartan against CCl4-induced liver fibrosis
Preparation and Evaluation of Voriconazole as Topical Organogel
Triazole antifungal drug voriconazole inhibits the fungal ergosterol synthesis and reacts very well against a wide range of fungal species. Organogel is a semisolid preparation in which the polar phase becomes immobilized within the three-dimensional structure. It would be ideal to have a topically applied form of voriconazole organogel to avoid undesirable systemic side effects and to reduce the dosage by coming into direct contact with the pathological site. This study aimed to formulate topical voriconazole organogel, consisting of a low molecular weight gelator (palmitic acid) at different concentrations with oleic acid, grape seed, and sesame oil. A solubility study revealed that voriconazole was highly soluble in the chosen oils. Several gelator concentrations were prepared by dissolving the drug in the oil at 85 °C, adding the gelator while continuously stirring for 40 minutes to obtain a clear solution, and then allowing the mixture to cool to room temperature to solidify. Formulas were prepared and evaluated based on their physical appearance, critical gelation temperature, spreadability, viscosity, pH, formulation, in vitro drug release study, antifungal study, and TEM. A compatibility study was conducted using Fourier-transform infrared (FT-IR) spectral analysis. An FT-IR study showed that the drug and excipients did not significantly interact. All the designed formulations of voriconazole show acceptable physical properties, pH, gel-solution, and solution-gel transition temperature. Viscosity and rheology studies demonstrated the pseudo-plastic shear thinning behavior of the organogels; among all formulations, palmitic acid with grape-seed oil at its critical gelation concentration (CGC) shows better drug release for sustained topical drug delivery; from the above observation results that this palmitic acid with grape-seed oil formulation might be a more promising topical treatment option for the recovery of skin fungal infections.
palmitic acid, voriconazole, organogel, grape-seed oil, gelator.
Nephroprotective Effect of Turkesterone Against Daunorubicin-Induced Acute Kidney Injury in Rats
Turkesterone, a phytoecdysteroid that possessing an 11-α-hydroxyl group, is an analogue of 20-hydroxyecdysone which is an insect steroid hormone. Phytoecdysteroids, a group of ecdysteroid hormones naturally in plant species Ajuga turkestanica, Rhaponticum carthamoides Willd. and Cyanotis arachnoidea C.B.Clarke that centuries used due to their tonifying, adaptogenic, and antioxidant and ability to enhance physical performance. ecdysterone and turkesterone have been associated with different biological effects, as neuroprotective, anabolic, antihyperlipidemic and antidiabetic. Several studies suggested that the mechanism of DNR-induced cardiotoxicity and nephrotoxicity by the formation of the reactive oxygen species (ROS) through their anthracycline–iron complexes redox cycling as well as of their aglycones that is the principal mechanism that induces their cellular damage. This study designed in order to investigate the possible nephron-protective of Turkesterone, against the nephrotoxicity induced by Daunorubicin. Twenty-four (24) adult Sprague- Dawley female rats. The animals divided to four (4) groups of six (6) rats for each: Group Ӏ: received oral daily dose of 10% dimethyl sulfoxide (DMSO) (4 ml/kg) for 15 consecutive days. Group ӀӀ: received single daily oral dose of 10% dimethyl sulfoxide (DMSO) for 15 days, then subsequently received Daunorubicin 20 mg/kg for the last 3 days with a cumulative dose of (60 mg/kg) by IP injection. Group ӀӀӀ: received oral dose of Turkesterone (5mg/kg/day) for 15 consecutive days. Group ӀV: received oral dose of Turkesterone (5mg/kg/day) for 15 consecutive days, then subsequently received Daunorubicin 20 mg/kg for the last 3 days with a cumulative dose of (60 mg/kg) by IP injection. Nephrotoxic rats, with daunorubicin, pretreated with Turkesterone (Group ӀV) was showed significantly decline in the serum level of both urea and creatinine, also reversed oxidative stress markers; rat Glutathione peroxidase 4 levels, to the control level. Suppression of the apoptotic and inflammatory markers, by measuring rat interleukin 6 levels and rat cleaved caspase-3 levels respectively, in kidney tissues.
The Perceptions and Acceptance of General Population toward the National Health Insurance Program in Iraq
The new Iraqi health insurance plan was approved by the Iraqi parliament in 2021 and became a law that should be implemented in the next couple of years. This study is collaboration between the University of Baghdad/ College of Pharmacy and the Health Insurance Authority which is the responsible body for the new health insurance program implementation. The study aimed to measure the general population's awareness and acceptance of the new national health insurance program in order to get over any obstacles that might arise during the implementation process. This study was a cross-sectional study using an electronic survey for the general population. A Google Form was used to distribute the survey via social media platforms. The survey items were adopted with modifications from a previous study to measure general population awareness, perceived benefits, and challenges that may face the implementation. The recruitment of participants took place from February 2023 to September 2023. The study received 562 completed surveys and the majority were female (63.7%). More than half (55.5%) were university students and 24.4% were government employees. The majority were from Baghdad (61.2%). More than half (54.6%) of them were unaware of the details of the new Iraqi health insurance law. More than three-quarters (76.7%) supported and were willing to join the new insurance plan. Most of the participants (68.5%) considered paying 1% of their salary per month to be reasonable. About 71.2 % of them believe that the quality of service would improve in the public sector and create competition with the private one by the implementation of the health insurance law. About 42% of the participants were dissatisfied with the health services in the private sector compared to the cost they paid; on the other hand, 56% were dissatisfied with the current semi-free health services in the public sector. In general, there is positive perception among the general population regarding the new health insurance plan particularly to enhance the quality and overuse of the current healthcare services. Low satisfaction with the current services and the affordability of the new health plan would encourage people to join the program. General populations need more advertising campaigns to be aware of the details of the health insurance program.
Acceptance, awareness, challenges, general population, Iraqi Health insurance law.
Acceptance, awareness, challenges, general population, Iraqi Health insurance law