Turkish Journal of Pharmaceutical Sciences最新文献

Objectives: Famciclovir, the drug of choice for cold sores and recurrent genital herpes, has poor oral bioavailability and is associated with numerous side effects. The study aimed to explore the possibility of transdermal application of famciclovir through a transferosome-loaded gelling system to localize the drug at the site of application with improved penetrability, therapeutic effects, and comfort.

Materials and methods: Transferosomes of famciclovir were prepared using tween 80, phospholipid, and cholesterol. To optimize drug entrapment and the vesicular size of the transferosomes, a central composite design was employed. The optimized formulation was evaluated for physicochemical characteristics, surface morphology, and degree of deformability. The optimized product was included in the Carbopol 940 gelling system. The gel was evaluated for ex vivo permeation, skin irritation, drug deposition at various skin layers, and histopathological analysis.

Results: The design optimization yielded an optimized product (FAMOPT) of nanosized (339 nm) stable vesicles of the transferosome of famciclovir. The surface morphology analysis revealed the formation of nanovesicles without aggregation. Compatibility between the drug and excipients was established. The elasticity of the vesicles demonstrated resistance to leakage. The permeation of the drug was enhanced by 2.8 times. The gel was found to be non-irritating and non-sensitizing to the animal skin. The drug deposition at various skin layers was remarkably improved, indicating effective drug penetration. The histopathological examination further demonstrated the penetration of nano-vesiculate drugs through deeper layers of the skin.

Conclusion: Hence, nano-vesicular famciclovir delivery is a promising alternative to conventional famciclovir delivery with enhanced local and systemic action for herpes treatment.

Objectives: The objective of the present study was to develop natural excipient-based solid lipid nanoparticles (SLN) of butenafine hydrochloride (BUTE) using a modified solvent emulsification technique and to evaluate the competence of aloe vera nanolipidgel in enhancing the penetration of BUTE.

Materials and methods: BUTE-SLNs were prepared using a 23 factorial design to correlate the effect of formulation components on the BUTE-SLN. Particle size, polydispersity index (PDI), zeta potential, entrapment performance, and drug loading were assessed in the formed SLNs. The fabricated BUTE-SLN was evaluated for transmission electron microscopy, fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction study studies and revealed the encapsulation of BUTE in lipid in the amorphous state. BUTE-SLN-based aloe vera gel was formulated and evaluated compared with the marketed product with respect to primary skin irritation, hydration, skin permeation, and antifungal activity.

Results: The BUTE-SLN aloe vera gel, optimized for its formulation, features excellent slip properties and controlled drug release. DSC and XRD studies confirm its amorphous nature with effective drug entrapment. The gel provides enhanced skin deposition, improved antifungal activity, and reduced irritation. This makes it a cost-effective and innovative alternative to traditional dosage forms. BUTE-SLN promisingly showed no irritation, higher hydrating potential, slow and sustained release, and enhanced antifungal activity. With an aim to target deeper skin strata, minimize the side effects of drugs and symptomatic impact of fungal infection, and shorten the duration of therapy, BUTE-SLN was successfully prepared. The mean particle size and PDI were 261.25 ± 2.38 nm and 0.268 ± 0.01, respectively.

Conclusion: BUTE-SLN gel offers improved topical delivery of BUTE with significantly higher compatibility and antifungal activity than the marketed formulation.

Objectives: Previous studies have shown that gene expressions can be regulated in the hippocampus of rats after seizures induced by kainic acid (KA). The aim of this study was to examine the potential regulatory impact of KA administration on gene expression levels of enzymes responsible for drug metabolism in rat hippocampal tissue.

Materials and methods: Rats received intraperitoneal injections of KA and saline at a dose of 10 mg/kg. Behavioral changes were observed in experimental animals following the administration of KA. Four hours after receiving treatments, all rats were decapitated, and the brains were removed. Hippocampal tissues were used for total RNA isolation, and cDNA synthesis was performed by reverse transcription polymerase chain reaction (PCR). Gene expression levels of enzymes responsible for drug metabolism were determined by quantitative PCR using the RT² Profiler PCR Array Rat Drug Metabolism PCR array system containing the relevant primers for a total of 84 genes. The gene expression levels of drug-metabolizing enzymes were quantified using the comparative Ct (2^{-ΔΔ(delta delta)Ct}) method. The Student's t-test was used for data analysis.

Results: Our results indicate that KA treatment caused significant changes in the gene expression levels of metallothionein 3, glucose phosphate isomerase, adenosine triphosphate-binding cassette protein C1, cytochrome P450 enzymes (Cyp2c6v1, Cyp3a23/3a1, Cyp2c7), glutathione peroxidase 1, 4, and 5, glutamic acid decarboxylase 1 and 2, paraoxonase 2, carbohydrate sulfotransferase 1, glutathione S-transferases (Gsta3, Gstm1, Gstm4), microsomal glutathione S-transferase 3, carboxylesterase 2C, fatty acid amide hydrolase, pyruvate kinase-muscle, arachidonate 5-lipoxygenase, apolipoprotein E, cytochrome b5 reductase 5, xanthine dehydrogenase, N-acetyltransferase 1, glucokinase regulator, hexokinase 2, myristoylated alanine rich protein kinase C substrate, and stannin in the hippocampus compared with the control (p < 0.05).

Conclusion: As a conclusion, it can be said that the seizure activity triggered by KA has the potential to change the gene expression levels of the enzymes responsible for drug metabolism in the hippocampus of rats.

Objectives: The study is aimed to investigate the association between different corticosteroid treatment regimens and clinical status, complications, mechanical ventilation requirement, and intensive care unit (ICU) mortality in individuals diagnosed with Coronavirus Disease of 2019 (COVID-19).

Materials and methods: This is a descriptive retrospective study. Patients admitted to the ICU for COVID-19 and treated with low- or medium-dose corticosteroid therapy (methylprednisolone at a dose of 0.5-1 mg/kg for 7-10 days) were compared with patients treated with high-dose pulse corticosteroid therapy (methylprednisolone at varying doses of 250 mg, 500 mg or 1000 mg for 3-7 days) in addition to standard therapy because of increased pulmonary infiltrate and elevated inflammatory markers during clinical monitoring. All demographic and clinical data, including age, sex, clinical course, laboratory findings, discharge status, 28-day mortality, intubation status, acute physiological assessment and chronic health evaluation II score, Charlson Comorbidity Index, and sequential organ failure assessment score, were recorded.

Results: Corticosteroid treatment was administered to 689 (88.3%) of 780 COVID-19 ICU patients between April 2020 and October 2021. The overall mortality rate was 45.1% (n= 352). When the mortality rates of patients were compared according to the corticosteroid dose, the mortality rate in the low-to-medium-dose group (40%) was significantly lower than that in the high-dose group (76%). In addition, significant deterioration in laboratory and clinical parameters was observed in the high-dose corticosteroid group.

Conclusion: High mortality, adverse effects, and complications were significantly increased when high-dose corticosteroids were administered. Corticosteroid therapy should be used cautiously according to the patient's clinical condition, disease stage, comorbidities, and systemic or organ reserves.

Objectives: Psoriasis is a chronic inflammatory, T-lymphocyte immune-mediated skin disease. In this study, skin-permeating nanolipid carriers (NLCs) of Methotrexate (MTX) and Baicalin (BL) were formulated. This further gave formulation of nano-lipid encapsulated carriers for dual-drug delivery of the hydrophilic and hydrophobic drugs through the liposomal gel.

Materials and methods: Optimization of the formulation of NLCs was performed and characterized by determining their particle size, drug permeation, skin irritation, drug loading capacity, stability, in vitro drug release behavior, and in vitro cellular viability. Ex vivo skin permeation and in vivo psoriatic efficiency were also evaluated and compared.

Results: Results revealed that the amount of MTX permeating the skin was 2.4 to 4.4 fold greater for dual-drug s than for single NLCs. The optimized dual-drug loaded NLCs had an average particle size (150.20 ± 3.57 nm) and polydispersity index (0.301 ± 0.01) and high entrapment (86.32 ± 2.78% w/w). The MTX nanoparticles exhibit a positive Zeta potential of 38.6 mV. The psoriasis area and severity index scoring showed the lowest skin erythema, skin thickness and scaling. MTX-BL NLCs were inhibited the expression of inflammatory cytokines (tumor necrosis factor-alpha, and interleukin-17) .

Conclusion: It can be concluded that newer targeting strategies for NLCs for dual-drug delivery of nano-lipid carriers could be administered topically for the treatment of psoriasis.

Objectives: The study aimed to identify drug-related problems (DRPs) and risk factors associated with the emergence of DRPs in intensive care unit (ICU) patients.

Materials and methods: This retrospective study included patients in the anesthesiology and reanimation ICU of a university-affiliated tertiary care hospital. DRPs identified by clinical pharmacists were classified using the Pharmaceutical Care Network Europe Classification for DRPs version 9.1. The association between various patient-related factors, and having DRPs were evaluated.

Results: In total, 222 patients were included in the study, 128 of which were male (57.7%). The number of DRPs was 388 in 135 patients (1.75 ± 2.47 DRPs per patient). The group in which at least 1 DRP was identified, the duration of hospitalization was longer than in the group in which no DRP was identified (p < 0.001). In the groups in which there was the presence of mechanical ventilation support at admission or mortality, the mean DRP count was significantly higher than that in the other group (p < 0.05). Age, duration of hospitalization, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission had positive relationships with the DRP count, but the Glasgow Coma Scale (GCS) showed a negative relationship (p < 0.05). According to the binary logistic regression analysis (p < 0.001), in which the age of the patient, GCS score, APACHE II score at admission, duration of hospitalization, and presence of mechanical ventilation support at admission were included, only the APACHE II score at admission and duration of hospitalization significantly affected the emergence of DRPs. The major problem was related to treatment effectiveness (47.9%), followed by treatment safety problems (29.9%). The major causes of these problems were dose selection (44.0%) and drug selection (36.8). Interventions were made at the drug (97.2%) and prescriber level (2.3%). The acceptance rate of interventions and resolution rate of the DRPs were 93.6% and 85.1%, respectively. The top three medications that caused DRPs the most were as follows: meropenem, colistin, and piperacillin/tazobactam.

Conclusion: Clinical pharmacists can detect and treat DRPs quickly. Our analysis shows that clinical pharmacy services are needed in high-DRP wards like ICU.

Objectives: This study aimed to formulate a novel herbal mixture of Hypericum perforatum (H) and Melissa officinalis (M) and evaluate its toxicity, microbial load, and phytochemical content.

Materials and methods: Total flavonoids were measured using the AlCl₃/NaNO₂ complex formation method and colorimetric assay. The quercetin content of the herbal mixture was determined by reverse-phase high-performance liquid chromatography. The in vitro and in vivo safety of the herbal formulations were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acute oral toxicity analysis in the rat model, respectively.

Results: The formulated extract (HM), compared with the standard rutin extract, had a total flavonoid content of 15.29 ± 0.64 mg rutin per mL sample. Reverse-phase high-performance liquid chromatography revealed a quercetin content of 0.187 mg/mL. Microbial tests for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella spp. were negative. Colony counts for total aerobic microbial and yeast and mold counts were 10 in each case. The MTT assay (with up to about 5% v/v HM extract) using the NIH/3T3 cell line revealed no cell toxicity in the range of concentrations tested. Acute oral toxicity was tested in the Wistar rat model, and the LD₅₀ was 695.2 ± 7.5 mg/kg. The dry weight of the HM extract was 38.1 mg/mL.

Conclusion: Preliminary results proved the safety of the HM herbal mixture, with its toxicity and microbial load within the limits of accepted guidelines allowable for use in clinical trials.

Objectives: Antiviral therapy approaches have become significant strategies to combat antibiotic resistance. Metal ions, particularly iron, play crucial roles in metabolic activities and virulence of bacteria. Loading iron into siderophore molecules could potentially circumvent antimicrobial resistance. This study aimed to evaluate the antibiofilm and antimicrobial effects of deferoxamine (DFO), an iron chelator and natural siderophore, on antibiotic susceptibility in clinical methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Acinetobacter baumannii (CRAB) isolates.

Materials and methods: The in vitro antibacterial activity of DFO alone and in combination with vancomycin [VAN (30 μg)], amoxicillin (25 μg), colistin (10 μg), and imipenem (10 μg), was investigated against MRSA and CRAB isolates using the disk diffusion method. The spectrophotometric microplate method was used to detect the in vitro antibiofilm effect of DFO.

Results: DFO exhibited a synergistic effect with VAN, amoxicillin, and colistin and significantly disrupted mature biofilm formation in MRSA and CRAB isolates. Notably, the antibiofilm effect of DFO was more pronounced in CRAB strains.

Conclusion: These findings highlight the potential of DFO as an antibiofilm agent candidate and suggest that it can enhance the antibiotic susceptibility of certain microorganism species.

Objectives: Cosmetics are known to cause adverse events in users, and there is limited information on this topic both globally and in Türkiye. This study was conducted to assess the use of cosmetics, patterns, and characteristics of adverse cosmetic events (ACEs) among female nurses.

Materials and methods: This cross-sectional study was conducted from February to April 2022 among registered female nurses with at least 1 year of work experience in a tertiary care hospital in Adana, Türkiye. A validated questionnaire was used for data collection, which included 13 questions with three main sections. The first part comprised demographic variables and cosmetic uses, the second part addressed ACE, and the final section consisted of consultation types and reporting methods for adverse events adopted after experiencing ACE.

Results: Of the total 158 participants, 144 were included in this study, resulting in a response rate of 91.1%. All female nurses reported using cosmetics, and 26.4% (n= 38) reported experiencing one or more cosmetic ACEs. Itching, burning, and eczema were the most frequently observed ACEs. A higher proportion of ACEs were associated with face care products (18.4%) and deodorants (13.1%). More than half (57.9%) of the nurses did not consult with healthcare professionals after experiencing ACE. Moreover, most participants (47.4%) did not report ACE to healthcare authorities.

Conclusion: A considerable proportion of the participants reported ACEs. The underreporting of ACE was also highlighted in this study. The results also emphasize the need for a robust cosmetovigilance system.

Objectives: Endometrial carcinoma (EC) is a typical gynecological malignant tumor that occurs more frequently every year. Obesity is a significant contributor to the development of EC and its prognosis. Lipid metabolism and malignant tumors have a long history of association. Elevated cholesterol levels are made possible by adenosine triphosphate-binding cassette protein A1 (ABCA1) deficiency, which eventually promotes cancer cell survival. The aim of this study was to examine at the ABCA1 gene expression levels in EC patients. The relationship between ABCA1 and the occurrence, progression, and prognosis of EC is discussed in this article as a potential mechanism.

Materials and methods: The samples of 45 endometrial adenocarcinoma patients were retrospectively included in this study and they were further divided into Grade 1 (15), Grade 2 (15), Grade 3 (15) tumors, control group. Twenty-nine endometrial tissues without a confirmed diagnosis of endometrial cancer made up the control group. ABCA1 gene expression was examined using real-time polymerase chain reaction.

Results: According to the results, the gene expressions of the patient group were higher than the control group When each Grade was compared with the control group, statistically significant results were obtained. After analyzing the data, it was found that the patient group was generally higher than the control group (p < 0.05) and there were differences in the grades of the patient group (p < 0.05). When the ABCA1 expressions of the grade groups and control groups were compared separately, a difference was found between Grade 1, Grade 2 and Grade 3 and the control group (p= 0.0001).

Conclusion: According to the findings of our study, a key component in the growth of EC tumors is the increase in cholesterol production caused by a reduction in ABCA1.