Al Mustansiriyah Journal of Pharmaceutical Sciences

Oxaliplatin serves as the primary treatment option for colorectal cancer (CRC) at all stages. It induces acute cold-triggered neurotoxicity and chronic cumulative neurotoxicity, leading to potential dose adjustments and influencing patient quality of life (QOL). However, conventional strategies are lacking for effectively managing oxaliplatin-induced neurotoxicity (OIN).

This observational study is a prospective aimed at investigating the incidence and associated factors of OIN involving 120 patients with CRC at different stages under oxaliplatin-based chemotherapy. The demographic and clinical characteristics of the patients were collected using a preformed data information sheet. The frequency and associated factors were evaluated after the third cycle of the Oxaliplatin chemotherapy. Unfortunately, 84 patients (70%) developed neurotoxicity while 30% did not experience this side effect. None of the included demographic or clinical characteristics were significantly associated with the OIN. Thus, it did not appear to predict neurotoxicity risk in the studied population. Other factors such as genetics could have such an impact and need to be investigated.

Breast cancer is the most prevalent tumor diagnosed in women and the second cause of death around the world. Therefore, improving the prognosis and effectiveness of treatment for breast cancer requires more studies to understand the underlying molecular mechanisms of its pathogenesis.

Sirtuin 1 is a NAD+-dependent class III histone deacetylase enzyme that is involved in metastasis, apoptosis, tumor growth, and other carcinogenesis pathways. The precise function of Sirtuin1 in relation to breast cancer is yet unknown, and its impact is still debatable. The purpose of this study was to examine the effect of sirtuin1 downregulation on the expression level of p53, the tumor suppressor protein, and on the DNA polymerase delta1 (POLD1), the gene encoding the catalytic and proofreading subunit p125 of DNA polymerase δ, in order to determine the significant function of sirtuin1 in breast cancer. The expression level of proteins was determined by the western blot method. The results of the current study revealed that downregulation of SIRT1by the EX-527 compound in MCF-7 breast cancer cell lines resulted in increased expression of p53 and decreased expression of POLD1. This study suggested that sirtuin1 co-operate with POLD1 in the molecular mechanism of breast cancer; therefore, SIRT1 could be a promising potential target for breast cancer treatment in the future.

This study aimed to prepare an effervescent floating tablet to protect cefpodoxime proxetil (CP) from enzymatic hydrolysis and higher pH degradation in the lower parts of the gastrointestinal tract (GIT). CP was prepared as amorphous solid dispersion (ASD) with soluplus and Polyvinylpyrrolidone K30 (PVP K30) in a ratio of 1:1:1 by solvent evaporation technology.

Effervescent floating tablet formulations were prepared in different compositions and ratios by direct compression techniques using polyethylene oxide (PEO), hydroxypropyl methylcellulose K4M (HPMC K4M), sodium alginate (Na alginate) as a hydrophilic matrix, sodium bicarbonate (NaHCO3), and citric acid as a gas-generating agent. These formulations were evaluated for floating ability and in vitro drug release. Then, an optimized tablet was performed to determine the hardness, friability, content uniformity, weight variation, and swelling index. The optimum formulation showed good buoyancy properties and extended drug release characteristics for 24 hours (hrs). The post-compression evaluation's parameters are within the limits of U.S. Pharmacopoeia. According to these results, the development of effervescent floating tablets of CP prepared as ASD could be effectively applied.

Breast cancer is a diverse disease with high mortality rates, often due to metastasis. Breast cancer subtypes vary by the expression of progesterone receptor, human epidermal growth factor receptor 2, and estrogen receptor. About 15%-20% of breast cancer cases are triple-negative, which lack these receptors and have poor prognosis and limited treatment options. The Mitogen-Activated Protein Kinase, particularly p38, are involved in cellular responses and cancer progression.

The study aimed to compare the cytotoxic effects of the compound 2-(4-Chlorophenyl)-4-(4-fluorophenyl)-5-pyridin-4-yl-1,2-dihydropyrazol-3-one as a p38 mitogen-activated protein kinase inhibitor in Breast cancer cell lines (MCF-7 and MDA-MB-231). The half-maximal inhibitory concentration values were calculated using nonlinear regression analysis. The half-maximal inhibitory concentration of the investigated compound p38 Mitogen-Activated Protein Kinase inhibitor was 5.355 µg in MCF-7 cells, whereas in MDA-MB-231 cells, it was 1.419 µg. In conclusion, the compound showed higher sensitivity and effectiveness in triple-negative breast cancer cells than estrogen receptor-positive cells.

Background: Sexual dysfunction in men is a common problem of antipsychotic drugs for the treatment of schizophrenia. Mucuna pruriens seeds extract has a significant effect in enhancing sexual function and reproductive parameters. Furthermore, it may have a therapeutic impact on the damage induced by hormonal changes and reactive oxygen species (ROS) to the structure and function of sperm.

Aim of the study: The current study aims to assess the effect of Mucuna pruriens seeds extract on sperm parameters and oxidative stress in chlorpromazine-induced sexual dysfunction in male rats.

Methodology: Thirty male Wistar rats with average weight (150-200g) were divided into five groups (n=6). Group 1: Negative control group, rats that received distilled water for 52days; Group 2: Induction group, rats that received (20mg/kg) of chlorpromazine for 52 days; Group 3: treatment group with a low dose of Mucuna pruriens 500mg/kg for 22days Group 4: treatment group with a medium dose of Mucuna Pruriens 1000mg/kg for 22 days Group 5: treatment group with a high dose of Mucuna Pruriens 2000mg/kg for 22 days. A serum sample was collected to measure glutathione (GSH) and malondialdehyde (MDA) serum levels using the ELISA technique. Semen samples were collected to determine Sperm count, morphology, and motility.

Results: This study revealed that chlorpromazine administration deteriorated the testicular function of rats, resulting in a significant[P<0.05] decrease in GSH serum level(6.37±0.29IU/ml), an increase in MDA serum level(9.57±0.16nmol/ml), and a reduction in sperm parameters (count, motility, and morphology) in the induction group compared to the control group. Treated groups with Mucuna Pruriens showed a significantly increased GSH serum level, significantly decreased MDA serum levels, and improved sperm parameters (count, motility, and morphology) compared to the induction group treated with chlorpromazine.

Conclusion: The study concluded that Mucuna pruriens improves reproductive toxicity and testicular damage induced by chlorpromazine through oxidative stress reduction, increased antioxidant activity, and improved sperm parameters.

Ocular drug delivery is an interesting and unique field for formulation scientists because of the many physiological and anatomical barriers of the eye. Although the eye is easily available for topical application only low amount of the administered dose reach the ocular tissues. Most of the applied medication, in particular eye drops which comprise 90% of all ocular medications, easily removed by blinking, excessive tearing, nasolacrymal drainage and corneal barriers.

Enhance pre-corneal residence time in ocular tissues is required to enhance bioavailability and reduce instillation time. Among the strategies used to enhance pre-corneal residence time is using ocular inserts. They are sterile solid or semisolid preparations that usually placed in cul-de-sac of the conjunctiva to increase pre-corneal residence time of the loaded drug. They must be formulated at specific thickness, shape and size to avoid eye irritation once applied. They can also be used for sustained drug delivery to the eye and the possibility of application of more than one drug at the same time. In this review we will look into the types of inserts, mechanism of drug release from the inserts and their advantages and disadvantages. In addition, we will have a deep look into how nanotechnology improved ocular inserts and the new advances in this field.

Prodigiosin is a red bio-dye that is produced by Serratia marcescens and another bacterium. It is made up of a linear tripyrrole chemical structure and is classified as an alkaloid. Researchers paid attention to prodigiosin pigment due to its ability to exhibit a diverse range of biological actions, including antibacterial, antifungal, antimalarial, and anticancer properties.

Objective: This study aims to assess the effectiveness of prodigiosin in treating superficial infections caused by antibiotic resistant bacteria.

Methods: The red pigment found in bacterial biomass was identified as prodigiosin by studying its structure with UV-visible spectrophotometry and high-performance liquid chromatography (HPLC). The antibacterial activity against pathogenic bacteria was assessed in vitro using agar well diffusion method. A mouse experimental wound model was used to initiate infection by Pseudomonas aeruginosa and Staphylococcus aureus. The topical treatment was administered 4 hours after the injury and continued until the wound was fully healed.

Results: The pigment exhibited a maximum absorbance peak at 535 nm. All strains that were tested showed sensitivity and produced significant areas of inhibition zones against P. aeruginosa (16.50±1.36mm) and S. aureus (20.83±2.40mm). Topical applications of prodigiosin (0.1% prodigiosin in Vaseline) have been proven to be beneficial. The scar healing was completed, with no remaining lesions and no signs of redness. The highest rate of decrease was shown at 95 mg/ml for S. aureus (C0.003±0.003b) followed by P. aeruginosa (D0.02±0.008b).

Conclusion: Prodigiosin, showed great potential as a natural substitute for synthetic drugs due to its potent antimicrobial properties against superficial skin infections caused by bacteria.

People have known how to employ plants for the basic requirements of having healthy and beautiful skin since the dawn of humanity. Herbal formulations have always drawn a lot of attention due to their potent efficacy in improving primary health care because of better cultural acceptability, better compatibility with human body.

With minimal side effects compared to synthetic medications. Herbal face washes, creams and gels made of natural ingredients are used widely because they provide the skin with essential minerals and nutrients. Plant-derived ingredients, such as herbs, flowers, roots and essential oils, are largely reviewed in recent literature and utilized in natural topical products. This review focus on the general properties of gels, characteristics of gels, classification of gels, methods of preparation and evaluation. Also examples in natural ingredients prepared in topical gels with their applications. So, this review will help the researchers to find the way for further investigation about preparations and applications of topical herbal dosage forms.

Autism and Alzheimer's disease are neurological disorders associated with defects in certain areas of the brain which share common clinical signs like language impairment, executive function, physiological and pathological abnormalities, DNA methylation, myelin change, and abnormal Peripheral blood cells like B-cell and T-cells.

A genetic factor was proposed as the main cause of disease; however, the molecular mechanisms are still not well known. S-nitrosylation (SNO) in neuropathology targets key protein of gene mutations in patients that may lead to synaptic defects which return to the pathogenesis of Autism and Alzheimer's Disease, while phosphorylation of protein tau and the amyloid-β protein precursor (APP) has been showed to play vital role in neurodevelopmental disorder.

Additionally, neurite growth plays a role in brain enlargement during the first years of human life, typically expanding the anterior cortex of the brain. White matter in the brain and cerebellum appeared in more than half of the human brain that decreased with age, it was determined by a secret of myelin, tumor growth factor, cytokine, and release of kinase enzyme. in contrast, the gray matter was determined by ventricle region, area of cortex, neural stem cell, and thickness. Neurological disorders of mRNA may be due to limited social communication, and irregular behaviors in patients with autism and Alzheimer's disease. Despite that, scientists' efforts to identify management against the progression of this pathology, have only able to decrease some symptoms of autism and Alzheimer's disease are usually available, it’s important to need for additional therapeutic strategies for complications, so, the World Health Organization (WHO) has made this disease a public health priority. The time period specified for this review article lasted from 2013 to 2023.

Ketoconazole (KZ) is a useful antifungal drug belonging to the imidazole group. its clinical use has been limited due to poor absorption, as it is primarily absorbed in the stomach and upper small intestine. Once the drug passes through the stomach via gastric emptying, its absorption significantly decreases, leading to reduced bioavailability.

This study aimed to develop gastro-retentive mucoadhesive tablets by testing different drug-polymer ratios and assessing their physical and functional characteristics. Nine formulations (F1-F9) were created as gastro-retentive mucoadhesive tablets using sodium alginate (Na Alg) and Carbopol 934 (Carb 934). The powder blend was tested for flow properties, and the resulting tablets were assessed for thickness, hardness, weight variation, friability, mucoadhesion time, swelling index, mucoadhesive strength, and in vitro drug release. Results revealed that Carb 934's high molecular weight and cross-linking promote prolonged mucoadhesion, leading to extended drug release. Formulations with higher Na Alg contents demonstrated more swelling but less mucoadhesion time than those containing Carb 934. Together, Carb 934 and Na Alg provided controlled drug release due to the balanced properties of the polymers. This study explored mucoadhesive gastro-retentive tablets of ketoconazole, which showed enhanced gastric retention and extended release. These properties are expected to improve the drug’s absorption and bioavailability, potentially offering a more effective therapeutic option.

Background: Doxorubicin (DOX) is an effective chemotherapeutic agent but possesses a significant risk of inducing acute kidney injury (AKI). Unfortunately, it severely affects clinical outcomes and patient quality of life. Omega-3 is widely used as supplement due to its anti-oxidant, anti-inflammatory and anti-apoptotic properties.



Objective: This study investigates the potential protective effects of Omega-3 fatty acids against DOX-induced renal injury in male rats. Using a controlled experimental design and evaluate the histopathological changes.

Materials & Methods: Forty male rats were randomized into 5 equal groups each consisting of 8 animals as follows, Group I (control group), which received normal saline orally for 4 weeks followed by a single injection of NS intraperitoneally (IP), Group II (induction group), which received NS orally for 4 weeks followed by a single dose of DOX 15mg/ kg IP, Groups III, IV, V, which received oral doses of Omega-3 (100mg/ kg, 200mg/ kg, 400mg/ kg, respectively) for 4 weeks followed by a single dose of DOX 15mg/ kg IP. kidney from each rat were extracted and fixed in 10% neutral buffered formalin for histological examination using H&E stain.

Results: Omega-3 supplementation significantly preserved renal histological integrity. Group IV and V showed approximately normal renal tubules with normal glomeruli & mild vascular congestion and the normal collecting tubule & thick segment of loop of Henle. While severe vascular degeneration of the lining cells of the renal tubules with necrosis and marked tubular dilation of collecting tubules in DOX group compared to control group.

Conclusion: Omega-3 nephroprotective effects against DOX-induced toxicity reveals its multifaceted role in enhancing preserving histological integrity of renal tissues

Atorvastatin (ATV) is a synthetic lipid-lowering agent. According to the Biopharmaceutical Classification System (BCS), ATV is classified as a Class II compound characterized by low solubility and high permeability. Its oral bioavailability is relatively low, at 14%, due primarily to pre-systemic clearance within the gastrointestinal mucosa as well as extensive first-pass metabolism in the liver.

So, this research aimed to develop mucoadhesive tablets containing atorvastatin as fibres via the electrospinning technique for buccal application, aiming to reduce gastric irritation, first-pass metabolism, and enhance bioavailability. Then, three fiber formulations with constant amounts of atorvastatin (ATV) and polyvinyl pyrrolidine, which represent one part and four parts, respectively, and different ratios of soluplus (1:4:1, 1:4:2, 1:4:3) were prepared. They underwent different characterization tests such as Fourier transform infrared spectroscopy, differential scanning calorimetry, optical microscopic imaging, and scanning electron microscopy. The F1 fiber with a ratio of 1:4:1 formulation was further investigated and formulated into mucoadhesive buccal tablets. These tablets underwent various tests, showing satisfactory results. Fourier transform infrared spectroscopy and differential scanning calorimetry studies were harmonized by revealing the change that affirmed the hydrogen bonds more likely to be between ATV and polymers, which assured the amorphous form of fibers by differential scanning calorimetry. F1 fibers achieved 99.6% release of ATV, while F2 and F3 reached 49% and 38.97%, respectively. Also, fibers were examined under an optical microscope, and a scanning electron microscope showed successful fiber formulation and smooth surfaced fibers without any beads or drug crystals on the surface, respectively. Using a controlled flow pump, the buccal tablets (B1 and B2) containing fibers equivalent to 20 mg of ATV showed a slow release of 2.78 mg and 4.39 mg, respectively. In contrast, dissolution by a conventional method, B2 tablet, reached 11.28 mg within 4 hours. In conclusion, drug-loaded ATV fibers with the more stable amorphous form were successfully formulated and characterized, as demonstrated by FTIR and DSC. SEM images exposed fibers with a smooth surface without solid particles, and the successful formation of unidirectional buccal tablets.