Iranian Journal of Pharmaceutical Research最新文献

Background: Despite the advantages of direct intratumoral (IT) injection, the relatively rapid withdrawal of most anti-cancer drugs from the tumor due to their small molecular size limits the effectiveness of this method of administration. To address these limitations, recently, increasing attention has been directed to using slow-release biodegradable delivery systems for IT injection.

Objectives: This study aimed to develop and characterize a doxorubicin-loaded DepoFoam system as an efficient controlled-release carrier to be employed for locoregional drug delivery in cancer treatment.

Methods: Major formulation parameters, including the molar ratio of cholesterol to the main lipid [Chol/egg phosphatidylcholine (EPC)], triolein (TO) content, and lipid-to-drug molar ratio (L/D), were optimized using a two-level factorial design approach. The prepared batches were evaluated for encapsulation efficiency (EE) and percentage of drug release (DR) after 6 and 72 hours as dependent variables. The optimum formulation (named DepoDOX) was further evaluated in terms of particle size, morphology, zeta potential, stability, Fourier-transform infrared spectroscopy, in vitro cytotoxicity, and hemolysis.

Results: The analysis of factorial design indicated that TO content and L/D ratio had a negative effect on EE; between these two, TO content had the greatest effect. The TO content was also the most significant component, with a negative effect on the release rate. The ratio of Chol/EPC showed a dual effect on the DR rate. Using a higher percentage of Chol slowed down the initial release phase of the drug; nevertheless, it accelerated the DR rate in the later slow phase. DepoDOX were spherical and honeycomb-like structures (≈ 9.81 μm) with a desired sustained release profile, as DR lasted 11 days. Its biocompatibility was confirmed by the results of cytotoxicity and hemolysis assays.

Conclusions: The in vitro characterization of optimized DepoFoam formulation demonstrated its suitability for direct locoregional delivery. DepoDOX, as a biocompatible lipid-based formulation, showed appropriate particle size, high capability for encapsulating doxorubicin, superior physical stability, and a markedly prolonged DR rate. Therefore, this formulation could be considered a promising candidate for locoregional drug delivery in cancer treatment.

Background: Apoptosis is proposed as a possible mechanism for diabetes-induced hippocampal neuronal cell death. Numerous studies have suggested that the therapeutic properties of plants, such as antioxidant and anti-apoptotic, are effective in improving the complications of diabetes in the hippocampus.

Objectives: This study aimed to evaluate the anti-apoptotic properties of Peganum harmala (P. harmala) in the brain hippocampal cells of diabetic rats.

Methods: In this experimental study, 48 male Wistar rats were divided into six groups (n = 8) as follows: Control (C), diabetic (D), harmine (H), diabetic plus harmine (DH), seed extract (S), and diabetic plus seed extract (DS). A single dose of streptozotocin (STZ) (60 mg/kg) was enough to cause diabetes. Seed extract and harmine were given at 150 mg/kg and 6.5 mg/kg, respectively (daily by oral gavage for 28 days). The glucose levels in the blood were measured, and the histological staining of the hippocampus was examined. Percentages of apoptotic hippocampal cells were identified with flow cytometry. Bax and Bcl-2 expression was assayed via Real time- polymerase chain reaction (PCR) and Western blot.

Results: In DH (P = 0.001) and DS (P = 0.01) rats, the mean fasting blood glucose level significantly reduced compared with the D group. Bax and Bcl-2 expression at both mRNA and protein levels significantly differed between the D group and other groups (P = 0.01). Harmine and the seed extract considerably reduced the Bax/Bcl-2 ratio in the hippocampal cells compared to the D group (P = 0.001).

Conclusions: Streptozotocin-induced apoptosis in the hippocampus of diabetic rats was reduced by administering the seed extract of Peganum harmala. The P. harmala seed extract and its active ingredient, harmine, could be used as anti-apoptotic drugs.

Background: The use of police breath alcohol detectors in rat breath alcohol detection experiments has always been a challenge because of the small lung capacity and inability of rats to actively inhale. However, the method of using gas chromatography to detect blood alcohol concentration is time-consuming, complex, relatively expensive, and cannot achieve on-site detection and multi-point unlimited non-invasive detection.

Objectives: In this study, a laboratory method was validated for rat breath ethanol concentration (BrAC) measurement to estimate blood ethanol concentration (BAC) in rats.

Methods: The rats were placed in a gas collection bottle, the breath sample was drawn out with a syringe, and injected into the mouthpiece of the breath alcohol detector through a rubber tube. The results were immediately detected and automatically converted to BAC. Male rats were randomly divided into three groups. The control group received an intraperitoneal injection of normal saline, the liver injury group received an intraperitoneal injection of 50% Carbon tetrachloride (CCL4 1 mL.kg^-1), and the induction group received an intraperitoneal injection of phenobarbital sodium (75 mg.kg^-1). Western blot analysis was used to detect the protein expression of CYP2E1. Similar grouping and experimental methods were used for female rats.

Results: This method was reproducible. The metabolic activity of CYP2E1 was downregulated in the injury group and upregulated in the induction group, which was consistent with the results obtained for CYP2E1 protein expression.

Conclusions: Our results confirmed that the rat gas cylinder breath alcohol assay can be used for multiple detections with immediate and non-invasive determination of alcohol metabolizing capacity. This is important for studies that require repeated assessment of blood alcohol levels.

Background: The goal of this research was to design and characterize quercetin microemulsions (MEs) to resolve water solubility issues related to quercetin and improve transcorneal permeation into the eye.

Methods: MEs were prepared by the phase diagram method. Oily phase (oleic acid-Transcutol P), surfactant (Tween 80, Span 20), and co-surfactant (propylene glycol) were used to make a quercetin-loaded ME. The size of the droplets, their viscosity, pH, release, flux, and diffusivity were all measured.

Results: Droplet diameters in ME samples ranged from 5.31 to 26.07 nanometers. The pH varied from 5.22 to 6.20, and the release test revealed that 98.06 percent of the medication was released during the first 24 hours. The flux and diffusivity coefficients of the ME-QU-8 formulation were 58.8 µg/cm².h and 0.009 cm²/h, respectively, which were 8.8 and 17.9 times greater than the quercetin aqueous control (0.2 percent). The maximum percentage of drug permeated through rabbit cornea after five hours was 16.11%.

Conclusions: It is concluded that ME containing quercetin could increase transcorneal permeation and that permeation could be altered by any change in the composition of the ME formulation. This effect might be caused by structural alterations in the cornea caused by ME components.

Breast cancer is an invasive disease with a high prevalence among females. Despite various treatments, studies are still ongoing to find an effective treatment for this disease. This study aimed to synthesize a new series of diaryl benzo[d]imidazo[2,1-b]thiazole compounds containing aminoethoxy side chain and in vitro investigate their cytotoxicity on a human breast cancer cell line (MCF-7). Twelve derivatives (6a-6l) were synthesized from this scaffold, the structures of which were spectroscopically confirmed. The cytotoxic effects of the derivatives on the MCF-7 cell line were also assessed using the MTT assay. All these compounds showed a good inhibitory effect on the MCF-7 cell line, compared to that of tamoxifen. Compounds (6i) and (6j) showed higher cytotoxicity with relevant inhibitory effects of 81% and 73%, respectively.

Background: Diabetes mellitus (DM) is frequently linked with problems of several organ systems, including retinopathy, neuropathy, and nephropathy. Additionally, patients have changes in sexual functioning, such as decreased libido and fertility. Vincamine, a monoterpenoid indole alkaloid, has hypoglycemic and antioxidant effects.

Objectives: This research assessed the impact of vincamine on testicular dysfunction in alloxan-induced male rats by measuring fasting blood glucose, oxidative stress, seminal analysis, and histological examination of the testis.

Methods: Wister-albino male rats were randomized into the following groups at random: Untreated-healthy, untreated-DM, vincamine-treated (20 mg/kg) DM, vincamine-treated (40 mg/kg) DM, and clomiphene-treated DM (5 mg/kg). On day 14, rats were sacrificed, and semen/blood samples were collected. Sperm count, motility, and morphological abnormalities were noted by microscopic examination. The testis was examined histopathologically and assessed using Johnsen's score.

Results: Compared with the untreated diabetic group, a dosage of 40 mg/kg vincamine generate a significant reduction in fasting blood sugar (FBG). Compared with the untreated diabetic group, the vincamine-treated rats produced greater plasma testosterone levels and Johnsen scores. In the vincamine 20 mg/kg group, sperm concentration was higher than in the vincamine 40 mg/kg group.

Conclusions: It is possible that vincamine has a potential preventive effect against diabetes-related reproductive problems attributable to its antioxidant activity and capacity to restore testicular steroidogenesis.

Background: Androgen deprivation therapy (ADT) has been considered as a mainstay of treatment for advanced prostate cancer. Considering ADT for cancer patients is accompanied with many side effects, such as behavioral and neurologic side effects that adversely affect the quality of life.

Objectives: This study aimed to evaluate the effects of melatonin administration on sleep problems and mood changes induced by ADT in prostate cancer patients.

Methods: The randomized, double-blind, placebo-controlled trial was designed in the oncology-hematology outpatient clinic of Omid Hospital, Isfahan, Iran. After screening by the hospital anxiety and depression scale (HADS), patients were divided into either an intervention group receiving 6 mg melatonin daily for four weeks or an identical placebo. After that, patients were evaluated by the Pittsburgh sleep quality index (PSQI), the Hamilton Anxiety Rating Scale (HAM-A), and Beck Depression Inventory (BDI) questionnaires at baseline and after 4-week follow-ups.

Results: Forty-three patients, including 21 and 22 patients in melatonin and placebo groups, respectively completed follow-ups period. Melatonin administration significantly improved PSQI scores in four domains of sleep quality, sleep latency, sleep efficacy, and daytime dysfunction. After 4-week melatonin supplementation, the severity of depression and anxiety assessed by BDI and HAM-A questionnaires, respectively, decreased non-statistically significant in both melatonin and placebo groups.

Conclusions: In our study, melatonin supplementation ameliorated ADT-induced sleep problems in patients with prostate cancers; however, for more conclusive results, further future large and well-designed clinical studies is warranted.

Background: Using sports supplements is common among athletes. The presence of anabolic steroids in sports supplements as a hormonal contaminant can increase production efficiency. Since anabolic steroids cause health problems and result in positive doping tests in athletes, it is important to investigate their presence in the supplement preparations consumed by athletes.

Objectives: This paper aims to simultaneously determine ten anabolic steroids by high-performance thin-layer chromatography (HPTLC) method in sports supplements.

Methods: Chromatographic analysis was conducted on glass silica gel 60F254 plates. The extracts loaded on silica gel plates are subjected to programed multiple development (PMD) to separate anabolic androgenic steroids (AASs). Densitometric scanning is carried out at the wavelength of 245 and 366nm. The method was validated according to the ICH guidelines.

Results: Spots at retardation factor (Rf) 0.72 (elution system 1), 0.4 (elution system 1), 0.29 (elution system 2), 0.25 (elution system 2), 0.1 (elution system 1), 0.65 (elution system 2), 0.59 (elution system 1), 0.44 (elution system 1), 0.8 (elution system 3), and 0.82 (elution system 3) values were recognized as 19-nor androstenedione, 19-nortestosterone, methyl testosterone, clostebol, stanozolol, trenbolone enanthate, oxymetholone, oxandrolone, testosterone enanthate, and nandrolone decanoate, respectively. The linear ranges were 25 - 250 μg/mL for oxymetholone, 7 - 50 μg/mL for 19-nor androstenedione, 19-nortestosterone, and oxandrolone, and 3 - 20 μg/mL for methyl testosterone, clostebol, stanozolol, trenbolone enanthate, testosterone enanthate, and nandrolone decanoate. The developed method is validated by acceptable precision (CV < 20%) and good accuracy (94% < R < 114%). The value of limit of detection (LOD) for all derivatives was in the range of 0.02 - 0.16 μg/spot (20-160 μg/g of supplement), while limit of quantitation (LOQ) was found to be in the range of 0.06 - 0.5 μg/spot (60 - 500 μg/g of supplement). Fifty sports supplement samples as real sample were collected and analyzed. None of the samples screened positive using the HPTLC method.

Conclusions: In the present study, the fast, cheap, and simple HPTLC method could be used for the multi-residue analysis of ten anabolic androgenic steroids in sports supplements.

Background: Intrauterine hypoxia (IUH) increases the risk of cardiovascular diseases in offspring. As a reactive oxygen species (ROS) scavenger, polyamine spermidine (SPD) is essential for embryonic and fetal survival and growth. However, further studies on the SPD protection and mechanisms for IUH-induced heart damage in offspring are required.

Objectives: This study aimed to investigate the preventive effects of prenatal SPD treatment on IUH-induced heart damage in newborn offspring rats and its underlying mitochondrial-related mechanism.

Methods: The rat model of IUH was established by exposure to 10% O₂ seven days before term. Meanwhile, for seven days, the pregnant rats were given SPD (5 mg.kg^-1.d^-1; ip). The one-day offspring rats were sacrificed to assess several parameters, including growth development, heart damage, cardiomyocytes proliferation, myocardial oxidative stress, cell apoptosis, and mitochondrial function, and have mitochondrial quality control (MQC), including mitophagy, mitochondrial biogenesis, and mitochondrial fusion/fission. In in vitro experiments, primary cardiomyocytes were subjected to hypoxia with or without SPD for 24 hours.

Results: IUH decreased body weight, heart weight, cardiac Ki67 expression, the activity of SOD, and the CAT and adenosine 5'-triphosphate (ATP) levels and increased the BAX/BCL2 expression, and TUNEL-positive nuclei numbers. Furthermore, IUH also caused mitochondrial structure abnormality, dysfunction, and decreased mitophagy (decreased number of mitophagosomes), declined mitochondrial biogenesis (decreased expression of SIRT-1, PGC-1α, NRF-2, and TFAM), and led to fission/fusion imbalance (increased percentage of mitochondrial fragments, increased DRP1 expression, and decreased MFN2 expression) in the myocardium. Surprisingly, SPD treatment normalized the variations in the IUH-induced parameters. Furthermore, SPD also prevented hypoxia-induced ROS accumulation, mitochondrial membrane potential decay, and the mitophagy decrease in cardiomyocytes.

Conclusion: Maternal SPD treatment caused IUH-induced heart damage in newborn offspring rats by improving the myocardial mitochondrial function via anti-oxidation and anti-apoptosis, and regulating MQC.

Background: The prevalence of drug poisoning is on the rise in Iran due to the increased public access to drugs. A national drug poisoning registry system is a suitable tool for better management, control, and prevention of drug poisoning.

Objectives: This study aimed to propose a national drug poisoning registry model for Iran.

Methods: This was an applied research conducted in two major phases. In the first phase, all sources pertaining to drug poisoning registries were reviewed, and a national drug poisoning registry model was proposed. In the second phase, this model was validated and finalized using a researcher-made questionnaire and through a two-stage Delphi technique.

Results: The focus of national drug poisoning activities and registry management reached the 100% consensus of experts at the Drug and Poison Information Center of the Food and Drug Organization (Ministry of Health and Medical Education). Goals, data sources, registry system structure, data set, standards, data exchange, registry features, and processes of the proposed model also achieved unanimous expert consensus.

Conclusions: Given the importance of a national drug poisoning registry in gathering, storing, analyzing, and reporting the data of patients, it is essential to provide a framework for evaluating and controlling drug poisoning and for generating valuable data for decision-making. The model proposed herein can offer the information infrastructure for designing and implementing such a system.