Brazilian Journal of Pharmaceutical Sciences
Publicar trabalhos científicos com a finalidade divulgar os mais recentes avanços da área das Ciências Farmacêuticas no Brasil e no exterior.
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY. The on-line journal has open and free access.
Exploration of phytochemicals and antihyperlipidemic effect of crateva religiosa bark: in vivo mechanistic approach for management of hyperlipidaemia
The work investigated the presence of phytochemicals and antihyperlipidemic potential of the ethanolic extract of Crateva religiosa (CRETE). The extraction yield was found to be highest with ethanol (15.81% w/w), followed by ethyl acetate (11.98% w/w) and very poor in hexane (3.05% w/w), using as solvents of variable polarity. Quantitative phytochemical analysis revealed that CRETE consists of higher total phenolic content (81.19 µg/mg equivalent to gallic acid) and flavonoid contents (49.0 µg/mg quercetin equivalents) compared to the ethyl acetate extract. GC–MS analysis confirmed the presence of stigmasterol, gamma-sitosterol and lupeol as phytochemicals. In vivo studies demonstrated that 400 mg/kg of CRETE reduced the levels of triglycerides (155.9 ± 1.51 mg/dl), total cholesterol (234.27 ± 1.91 mg/dl) and low-density lipoprotein cholesterol (66.27 ± 2.07 mg/dl), while increased the level of high-density lipoprotein cholesterol (133.48 ± 3.72 mg/dl). Atherogenic indices were also improved significantly. CRETE restored hepatic architecture and reduced adipocyte size. CRETE also exhibited strong antioxidant effects by lowering malondialdehyde (MDA) levels and enhancing glutathione (GSH), superoxide dismutase (SOD) and catalase activities. Mechanistically, in comparison to control groups, CRETE inhibited HMG-CoA reductase activity (p < 0.0001) and up-regulated PPARγ (p < 0.01) and CCAAT/EBPα (p
Direitos autorais (c) 2026 Brazilian Journal of Pharmaceutical Sciences https://creativecommons.org/licenses/by/4.0/
Pɸ-mi-pa loaded PVA/HA electrospun nanofibers from a statistically designed experiment using machine learning algorithms
Bacteriophages, which infect bacterial cells, have a unique ability to reduce bacterial colonization, particularly in antibiotic-resistant biofilm infections. This study aims to fabricate optimized bacteriophage-loaded nanofibers composed of polyvinyl alcohol (PVA) and hyaluronic acid (HA) using machine learning techniques. A comparative analysis was conducted to determine the most efficient machine learning algorithm for this purpose. The eXtreme Gradient Boosting (XGBoost) algorithm was used to optimize three sets of bacteriophage-loaded nanofibers—GA1, GA2, and GA3—at varying sonication times. The nanofibers were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), mucoadhesion analysis, thermogravimetric analysis, tensile strength analysis, and a bacteriophage release assay. SEM analysis revealed that GA3 exhibited homogeneous, well-aligned, defect-free polymer fibers with smooth surfaces, whereas GA1 and GA2 contained bead-like structures. Thermal degradation occurred between 300 °C and 368 °C, with GA1 displaying the highest tensile strength. Predicted values for mucin adsorption and bacteriophage release closely aligned with experimental data, confirming the accuracy of the XGBoost model. Finally, the release of MDR-specific phage Pɸ-Mi-Pa from the optimized nanofibers was highest at pH 5, which is similar to vaginal pH. These findings highlight the potential of these nanofibers for phage therapy, particularly in improving the prognosis of antibiotic-resistant biofilm infections.
Creation of ceftazidime-avibactam utilization evaluation standards to examine physician prescribing compliance: a retrospective study
A study was conducted to create drug utilization evaluation (DUE) standards for ceftazidime-avibactam (CZA) and evaluate CZA use at the First Affiliated Hospital of Bengbu Medical University, China, from May 26, 2020, to December 18, 2024. First, we organized an expert panel and created DUE standards for CZA. Then, we performed an observational study and evaluated the physician CZA prescribing behaviors, which were compared to the DUE standards and calculated the compliance rates. The DUE CZA standards had medication indications, management metrics, administration process, and treatment outcomes. Sixty-four patients received the CZA during the study period. There was satisfactory compliance between CZA prescription and DUE standards regarding route, solvent, incompatibility, and contraindications. However, the compliance rates for CZA indication, dosage regimen, infusion time, combination therapy, drug interaction, and duration of treatment were 68.8% (44/64), 65.6% (42/64), 29.7% (19/64), 73.3% (44/60), 43.8% (28/64), and 62.5% (40/64), respectively. The pre-CZA bacteria culture test was 96.9% (62/64). In addition, medical records and prescription authorization were 95.3% (61/64) and 71.9% (46/64) compliant, respectively. No adverse reactions were reported. In conclusion, the CZA DUE standards could be applied to identify inappropriate prescriptions for improvements.
Effects of sea buckthorn granules on the lungs of rats with chronic bronchitis: a study based on the P38 MAPK/P65 NF-ΚB signaling pathway
This study was conducted to explore the mechanism of Sea Buckthorn Granules (SBG) in treating chronic bronchitis (CB) in rats. The primary chemical components of SBG were identified using UPLC-Q-TOF-MS/MS. A rat model of CB was established through smoke inhalation combined with lipopolysaccharide (LPS) stimulation, followed by oral administration of SBG. The serum levels of TNF-α, IL-6, and IL-1β in rats were measured using ELISA. Pathological changes in lung tissues were observed through HE and toluidine blue staining. Furthermore, the main components and pathways involved in the therapeutic effects of SBG on CB were predicted using network pharmacology. In addition, p38 and NF-κBp65 protein expression as well as their phosphorylation levels in rat lung tissues were measured by western blot. Compared to the model group, treatment with SBG significantly alleviated cough symptoms, and Mitigating body weight loss in CB rats (P
Intravaginal administration of metformin HCL loaded nanoemulgel for treatment of PCOS: in-vitro and in-vivo study
Metformin HCL (MET-HCL), is a Biguanide derivative, most effective agent in treatment of PCOS. The focus of the present study was on developing and optimizing a nanoemulsion formulation. of MET-HCL and convert into intravaginal MET-HCL Nanoemulsion Gel (MET-HCLNE GEL) To enhance the therapeutic efficacy in managing PCOS. The nanoemulsion was formulated using water titration method and evaluated for droplet size, zeta potential, polydispersity index (PDI), drug content, viscosity, and morphology. Then incorporated into gel and evaluated for pH, drug content, viscosity, in-vitro release & in-vivo study. The formulation MET-HCLNE 1 showed the desired droplet size (45.60 ± 1.7 nm), PDI (0.198 ± 0.2), zeta potential (22.4 ± 0.3), drug content (89.19 ± 0.2 %) and viscosity (42.85 ± 2.1 cp). In in-vitro release, MET-HCLNEGEL showed significant prolonged release over MET-HCL solution. Intravaginal MET-HCLNE GEL showed significant efficiency against PCOS compared to oral administration in female Wistar rats. No significant changes were found in the values of viscosity, drug content and pH over the period of 120 days. Thus, MET-HCLNE GEL was found to have good potential to function as an Intravaginal formulation & having great PCOS activity and good storage stability.
Simultaneous determination of venetoclax and obinutuzumab by LC-MS/MS and its application to pharmacokinetic drug interaction studies
A novel LC-MS/MS method was developed and validated for the simultaneous quantification of venetoclax and obinutuzumab in rat plasma and successfully applied to pharmacokinetic investigations in male wistar rats. Chromatography was performed on a Symmetry C18 column (150 x 4.6 mm, 3.5 µm) column utilizing multiple-reaction monitoring (MRM) mode to evaluate venetoclax, obinutuzumab, and the internal standard gossypol, following which they were extracted using liquid-liquid extraction. The assay demonstrated high sensitivity, excellent reproducibility, and full compliance with FDA bioanalytical validation criteria, with venetoclax exhibiting a linear range of 25–200 ng/mL and obinutuzumab 6.25–50 ng/mL, respectively. The high-abundant mass transitions were seen starting from 869.4425 and 603.8597 m/z for venetoclax and 146.5948 and 67.6239 m/z for obinutuzumab and Gossypol (IS) 519.5638 and 206.7486 m/z, respectively. Upon application, the study successfully characterized the pharmacokinetic profiles of venetoclax and obinutuzumab in Wistar rats, revealing differences in absorption and systemic exposure between the two compounds. Venetoclax demonstrated a higher Cmax and AUC with a delayed Tmax compared to obinutuzumab, although both shared a similar elimination half-life of 20 hours. The results indicate consistent and stable pharmacokinetic behaviour under the tested conditions, supporting future therapeutic drug monitoring and preclinical drug development.
Fully independent validation of the Matrix-INI, IMEPAG-group, MERIS instruments for predicting preventable drug-related incidents of hospitalized patients with infectious diseases
Validate and compare three prescription-related incident prediction instruments (Matrix-INI, IMEPAG-group, MERIS) in hospitalized patients with infectious disease. Observational follow-up (cohort) study enrolling adults from June 2019 to March 2020, with no prior care from the clinical pharmacist. Matrix-INI, MERIS, and IMEPAG-group instruments assessing preventable drug-related incidents (PDRI) were applied at ward admission and once a week. The outcome of interest was clinically relevant PDRI. For every participant at every time of analysis, the instruments scores were retrieved, and validation was estimated through calibration (slope, intercept), discrimination indexes, and reclassification indexes. 219 patients were screened, and 212 were included. PDRI affected 78.77% of participants. “Anticoagulants” was the strongest predictor. Discrimination of all instruments was always low. (area under ROC curve < 0.70); and weekly performance was insufficient. No reclassification improvement was observed. Matrix-INI, IMEPAG-group assigned lower risks despite PDRI. Discrimination increases slightly every week, with a corresponding calibration loss. Models lacked sufficient predictive performance, pointing to a need for a specific PDRI prediction tool for this population. Empirically developed instruments, such as Matrix-INI, often exhibit poor performance. Regular risk assessments during hospitalization are crucial for dynamic prioritization in clinical pharmacy, as PDRI risk may change over time.
Pedro Emmanuel Alvarenga Americano do Brasil
The qualifar-SUS program: an analysis of 10 years of the public policy
The National Program for the Qualification of the Pharmaceutical Services in the Unified Health System (Qualifar-SUS), established in 2012, aims to contribute to the process of implementation, improvement and systemic integration of Pharmaceutical Services (PS) activities in the municipalities, aiming to continuous, comprehensive care, qualifying management processes for adequate and safe access and use of medicines. This analysis sought to historically contextualize its formulation and expansion design throughout its ten years of execution in Brazilian municipalities. To this end, a documentary analysis was carried out with an essay discussion, organized in the items listed for the formulation of Public Policies. Documents published in the period from 2008 to 2021 by the federal government, organized entities of managers, thematic magazines on management, and reports from auditory sessions of the federal court of accounts were read. With the analysis of these documents, it was possible to visit details of the creation, implementation and execution of government actions in addition to the texts of ordinances, resolutions and published regulations. This analyses made it possible to make notes about the program, its actors and arenas so that they can serve as a tool to strengthen access to medicines in Brazil.
Gas chromatography-mass spectrometry profiling and assessment of antiulcer and antioxidant activities of methanol extract from Dioscorea praehensilis rhizomes
Peptic ulcer is a common disease in gastroenterology clinics. This study aimed to investigate the chemical composition, antiulcer, and antioxidant activities of methanol extract of Dioscorea praehensilis rhizomes. The rhizomes were extracted by macerating in 80% methanol and subjected to chemical profiling using Gas Chromatography-Mass Spectrometry (GC-MS). The assessment of anti-ulcer activity was done using ethanol and indomethacin-induced gastric ulcer models in rats while the antioxidant studies were conducted using quantitative analysis of phenolic (total phenols and total flavonoid) compounds, 1,1-diphenyl-2-picrylhydrazyl (DPPH), total antioxidant capacity (TAC) and ferric ion reducing antioxidant power (FRAP) assays. D. praehensilis extracts at 125, 250, and 500 mg/kg ‘per os’ (PO) exhibited a significant (p<0.01) dose-dependent decrease in gastric lesions with the percentage inhibition of 65.16, 68.20, and 79.64% respectively in the ethanol model and 81.89, 90.44, and 95.35% in the indomethacin model compared with the control group. D. praehensilis extract contained high phenolic and flavonoid content. The extract also showed considerable antioxidant activity in the DPPH, TAC and FRAP assays. Furthermore, D. praehensilis contains bioactive constituents such as Pentadecanoic acid, 9-Eicosene, n-Hexadecanoic acid, 4-tert butylphenol and Pentacosane. In conclusion, D. praehensilis possesses antiulcer and antioxidant activity, supporting its traditional use in treating ulcers and dyspepsia.
Herbal Medicine Around the World: How Brazil, India, the USA, and Europe Regulate It
Herbal medicines (HM), derived from whole plants or their parts, play a crucial role in primary health care, with approximately Eighty percent of the global population relying on them. The World Health Organization (WHO) is tasked with establishing guidelines for their use, safety, and quality. Despite these standards, risks associated with self-dosing and variability in regulatory frameworks persist. Regulatory approaches differ worldwide, including Brazilian legislation through ANVISA, Indian regulations under the Drugs and Cosmetics Act, the European Medicines Agency (EMA), and the US Food and Drug Administration (FDA). Each framework enforces high standards for quality, safety, and efficacy, involving rigorous testing on human subjects. While significant strides have been made in standardization and therapeutic consistency, challenges remain. Integrating international standards aims to address these issues, focusing on reducing the risks associated with unsafe and ineffective herbal medicines for consumers. Our review tries to reflect on the various herbal regulations across Brazil, India, European Union, and USA and bring out a comparative opinion on various aspects as well as the need for harmonization of these regulations.
Protective effects of bromelain in LPS-induced acute lung injury
Acute lung injury (ALI) is a severe disease that can cause extensive lung damage and lead to death. Elevated levels of inflammatory cytokines and associated inflammation and oxidative damage irreversibly damage the lung tissue, leading to death. This study aimed to utilize the powerful antioxidant properties of bromelain (BRO) in ALI to determine its beneficial effects. We used an LPS-induced ALI model in rats, and 40 male specimens were divided into five groups: Healthy, Healthy+100BRO, ALI, ALI + 50BRO, and ALI + 100BRO. At the end of the study, histopathological and biochemical analyses of the lung tissue samples were performed. The results showed that tumor necrosis factor, interleukin-1, interleukin-6, and malondialdehyde levels increased in the ALI group and that these levels decreased dose-dependently with BRO treatment. We also demonstrated that superoxide dismutase levels, which decreased in the ALI group, increased dose-dependently in the BRO treatment groups. Histopathologically, significant improvement was detected in the BRO treatment groups. As a result of this research, it is suggested that BRO should be considered as supportive therapy in ALI. However, more detailed experimental and clinical studies on this subject are needed.
Formulation and evaluation of niosomal gel containing apremilast: optimization, in-vitro release and skin permeation studies
The objective of this study was to develop, optimize and evaluate Apremilast niosomes integrated into a topical gel for improved skin permeation. Niosomes were prepared by thin film hydration technique using cholesterol and Poloxamer 188. Niosomes optimization was employed using Box-Behnken Design wherein three variables cholesterol concentration, Poloxamer 188 concentration and stirring speeds were studied on responses entrapment efficiency, particle size, drug release, and release kinetics. The optimized niosomes were further evaluated for zeta potential and surface characterization by transmission electron microscopy. The selected niosomes were loaded into Carbopol based gel and evaluated for appearance, pH, rheology, in vitro drug release and ex vivo skin permeation studies on excised rat dorsal skin. The niosomal formulations by BBD design exhibited entrapment efficiencies ranging from 53.43% to 76.36% and particle sizes from 204 nm to 282 nm. Sustained drug release profiles were observed, with drug release percentages between 60.01% and 99.11% after 10h. Based on the opted design space and experimentation, optimization of niosomes by thin film hydration using BBD was achieved. The optimized niosomes were assessed for particle size (274.7 nm), zeta potential (37.6 mV), entrapment efficiency (68.29%), drug release (88.36% after 10h), transmission electron microscopy (uniform distribution with spherical shape) and drug release kinetics showing Korsmeyer-Peppas (non-fickian) model as best fit for drug release. The niosomal gel was formulated with acceptable characteristics for appearance (uniform gel, without phase separation), pH (6.91), viscosity (1498.7 Pa.s) and drug content (96.5%). Similarly, conventional Apremilast gel was also prepared for drug release and skin permeation comparison. The in vitro release experiments indicated consistent and sustained drug release for 6h with 83.5% drug release compared to conventional gel which showed 3h with 97.1% of drug release. Skin permeation studies showed improved deposition of Apremilast with niosomal gel in the skin (1750µg) compared to the conventional gel formulation (731µg), indicating improved skin permeation and deposition of Apremilast in the skin by niosomal drug delivery. The results emphasize the potential of niosomal gel formulations for enhancing topical delivery of Apremilast. The optimized niosomes loaded into topical gel system improved skin permeation and drug deposition with the layers of the skin. These attributes show the potential to improve drug delivery across the skin for poorly permeable drugs. Future research shall focus on in vivo studies to establish efficacy and safety for therapeutic applications.
An overview of Salmonella biofilms and their inhibition by plant bioactive compounds
Microbial biofilms are ubiquitous and highly successful forms of life. Among them, species found in food industries often include human pathogens like Salmonella spp., a significant concern due to its ability to adapt and survive in diverse environmental stresses. This bacterium is a major global public health issue, causing foodborne illnesses with considerable morbidity and economic costs. Combatting bacteria within biofilms necessitates novel strategies, and recent research highlights natural compounds as promising agents due to their antibiofilm, antivirulence, and antimicrobial properties. Specifically, plant-derived compounds have shown potential to modulate biofilm formation either alone or in combination with other substances. This review provides a comprehensive overview of Salmonella biofilms, encompassing their development, composition, resistance mechanisms, and tolerance mechanisms. It focuses particularly on the inhibition of these biofilms by plant-derived compounds.
Pharmacotherapy follow-up in hiv-positive patients: impact on mental health and quality of life
Research on anxiety and its treatment among HIV-infected individuals is limited, despite its high prevalence. HIV-positive patients often consume many anxiolytic/hypnotic medications. Pharmacotherapeutic monitoring and multidisciplinary pharmaceutical intervention can improve treatment adequacy, health education, detection of inappropriate prescriptions, drug interactions, patient satisfaction, reduce morbidity and mortality and general health care costs. The objective of the study was to evaluate the impact of pharmacotherapeutic monitoring on the rational use of anxiolytics/hypnotics in HIV-positive patients on antiretroviral therapy. Three pharmaceutical consultations were carried out according to the Dáder method, using the STAI (State/Trait Anxiety Inventory) to assess anxiety levels, and pharmaceutical interventions were carried out. In the first pharmaceutical consultation, all patients presented severe anxiety. In the third consultation, the average was statistically lower in the two anxiety conditions evaluated. In the group of patients where health problems were resolved or partially resolved there was a lower level of anxiety, suggesting that the resolution of health problems through pharmaceutical interventions promoted a reduction in anxiety. It was concluded that pharmaceutical assistance provided through health education integrated with pharmacotherapeutic monitoring using the Dáder Method has a positive impact on the rational use of anxiolytics/hypnotics in HIV-positive patients on antiretroviral therapy.
Triggers of drug-related bleeding events: a systematic review
Adverse drug events (ADEs), such as drug-related bleeding (DRB), represent a serious public health issue and highlight the role of triggers in pharmacovigilance. This study aimed to identify the triggers used to detect inpatient DRB. A systematic review was conducted and registered in PROSPERO (CRD42023440337). The search included the databases PubMed, LILACS, Cochrane Library, Embase, and Web of Science, covering published studies on ADEs in hospitalized adults focused on DRB triggers, with no language restrictions, up to September 2024. Methodological quality was assessed using the Joanna Briggs Institute tool, and trigger performance was evaluated by Positive Predictive Value (PPV). Twenty-three studies were included, identifying 28 triggers for DRB with PPV ranging from 0% to 100%. Prolonged INR and PTT were the most high-performing laboratory triggers, while textual triggers have demonstrated their potential, despite requiring adjustments to avoid false positives. A multimodal approach of laboratory and textual triggers combined emerges as beneficial to ADEs surveillance. Standardized and rigorous methodologies are recommended to strengthen evidence and guide clinical interventions.
Drug-related side effects and adverse reactions
Ana Helena Dias Pereira dos Santos Ulbrich
Recent advances in paclitaxel polymer nanomedicine delivery for cancer therapy
Paclitaxel (PTX) is a widely used anti-tumor drug in cancer therapy. However, its poor water solubility restricts its application in therapeutic procedures. Furthermore, the Cremophor® in the formulation can cause various side effects, leading to non-specific drug distribution in tumors and normal tissues. To overcome these limitations, researchers have explored numerous drug delivery systems to enhance the solubility of PTX and achieve targeted delivery. One such strategy involves using polymer nanoparticles, tiny particles composed of polymers that encapsulate and stabilize PTX, thereby improving its solubility and bioavailability. In addition, these polymer nanoparticles can enhance the therapeutic effect of PTX through passive targeting and active targeting mechanisms. This review first highlights the challenges of paclitaxel in current applications, focusing on current synthetic advances in PTX and drug resistance; subsequently, various approaches to deliver PTX using polymer Nanoparticles are discussed. Finally, current challenges and prospects are reviewed. Our goal was to demonstrate how these different nanocarriers can improve the therapeutic efficiency of PTX as a chemotherapeutic agent.
Biological evaluation of thiazolopyrimidine derivatives as novel heterocyclic compounds against promastigote and amastigote-like forms of Leishmania infantum and Leishmania tropica
Leishmaniasis is an underfunded neglected disease that affects 12 million people mainly living in developing countries. Herein, based on the data we obtained in our previous study, we designed and synthesized novel thiazolo[5,4-d]pyrimidine derivatives and evaluated their in vitro antileishmanial bio-activity. The compounds were synthesized, and their structures were elucidated. Then, their anti leishmanial activities were tested using both promastigote and amastigote-like forms of L. tropica and L. infantum parasites. Additionally, we evaluated the in silico physicochemical properties and the structure-activity relationships of the compounds. Compound 4-chloro-N-[5-(4-hydroxypiperidin-1 yl)thiazolo[5,4-d]pyrimidin-2-yl]benzamide (A1), with IC50 values of 43.58 µM and 41.45 µM against L. tropica and L. infantum promastigotes, respectively, and 70.02 µM and 77.13 µM against L. tropica and L. infantum axenic amastigote-like forms, was found to be the most active compound in both assays. Compound A1 also exhibited the lowest iLogP value among the compounds, suggesting high passive gastrointestinal absorption. Based on both in vitro assays and in silico properties, compound A1 demonstrates significant anti-parasitic activity and serves as a promising lead for the development of new antileishmanial agents.
Enhancement of irinotecan oral bioavailability through quality by design approach in nanobubble formulation development
Irinotecan (IRO), a potential drug approved by the USFDA used in colorectal cancer, hinders its therapeutic applications due to low solubility and very poor bioavailability. The current research aims to use Dextran sulphate (DEX) nanobubbles (NBs) as a delivery system for IRO to improve the bioavailability and enhance its beneficial effect. Using emulsification technique we formulated IRO-loaded dextran sulphate NBs and optimized utilizing a Box Behnken design with input of process and formulation parameters. The characterization of NBs checked for particle size, drug loading, entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), X-ray diffraction studies, and also stability studies, in vitro and in-vivo studies on rats. The optimized NBs presented 89.8 ± 9.5 nm of particle size, -18.6 ± 1.2 mV of zeta potential, and 0.284 ± 0.108 of polydispersity index. NBs showed 72.86 ± 1.54% of entrapment efficiency and 33.57 ± 2.10% of drug loading, while in vitro study showed that ultrasound enhanced the release of drugs by 99%, compared to plain drug, which was only 35%. Characterization studies confirmed the absence of drug-polymer interaction. In conclusion, the findings of this study suggested that this type of formulation might be an alternative for cancer treatment.
Dry powder inhalation for sildenafil citrate: formulation and performance tests
Pulmonary arterial hypertension (PAH) is a severe disease responsible for high mortality in the affected population. Due to the limitations in treatment as severe adverse effects, high cost, we aimed to develop a simple therapeutic option for pulmonary administration, using a vasodilator sildenafil citrate (SILC) in a dry powder inhalation using lactose as carrier. A formulation of micronized SILC was prepared after 30 min wet grinding of the active with the aid of a vibration shear-mill. Solid characterization by laser diffraction and X-ray powder diffraction was assessed for active. Performance tests such as delivered-dose uniformity (DDU) and aerodynamic particle size distribution (APSD), using Dosage Unit Sampling Apparatus and Andersen Cascate Impactor, respectively, were performed. The micronization of SILC resulted in a medium size of 4.54 µm and a 50th percentile of 2.93 µm. For DDU, the total amount delivered ranged from 92.42 to 109.05% of the targeted dose, in agreement with the specified range (75.0-125.0%). For ASPD, a fine particle fraction of 35% was satisfactorily obtained. This formulation is simple and promising therapeutic option for the treatment of PAH with the advantage of being easily produced using less complex carrier matrix or equipment, in a short time.
Jackson Antonio Lamounier Camargos Resende
Microemulsion-based dual delivery of malkangani and phalsa: formulation, optimization and in-vivo pharmacodynamics in rats
Alzheimer’s Disease is a prevalent form of dementia typically characterized by neurodegeneration, memory loss and cognition loss. Celastrus paniculatus (malkangani) is a well-known brain tonic in Ayurveda, while Grewia asiatica (phalsa) is reported to improve memory and cognition. This study was focused on the development and evaluation of a combined microemulsion of phalsa extract and malkangani oil. The microemulsion was prepared using the water titration method and optimized using Box Behnken Design. The optimized formulation showed particle size of 14.91±0.20 nm, 0.323±0.03 polydispersity index (PDI) and % transmittance of 96.31±0.04 %. The in-vitro drug release was estimated by media change method in 0.1 N HCl and phosphate buffer (pH 6.8) and it found to follow Higuchi order kinetics with about 90 % release up to 8 hrs. Microemulsion significantly improved inflexion ratio in elevated plus maze test; indicating improvement in learning, memory and recognition in scopolamine-induced amnesia in rat as compared to single treatment of oil or extract, however statistically non-significant effect was seen in novel object recognition test. The biochemical tests and histopathological examinations of rat brains also showed the effect of microemulsion when compared to the disease control group. This combination in microemulsion can be used as a prophylactic treatment to prevent neurodegeneration.
Revolutionizing HIV/aids treatment: advances in CRISPR/Cas9
Human immunodeficiency virus (HIV) is a significant health issue globally and affects millions of people worldwide each year. The infection is treated using antiretroviral therapy (ART) and considered as standard treatment for HIV. The therapy consists of a combination of medicines that slow down or suppress the replication of the virus. Although ART therapy has been successful in managing HIV infection it is not the cure and requires life-long adherence to remain effective. Hence scientists and health workers around the globe are looking for more effective therapy that eliminates the virus from the patient body. Genomic medicine is one of the most significant therapies among these novel treatment procedures. The current advances in genomic medicine and genetic engineering, especially the discovery of CRISPR/Cas9 offer new hope to fight against HIV. In this study, we investigate the current advances in CRIPSR/Cas9 base therapy against HIV. Further, the basics of CRISPR/Cas9 technology, its application in HIV research, challenges, and future perspectives were also investigated.
Development of dextran based nanomicelles in a dry powder formulation for pulmonary administration of niclosamide
Inhalable dry powders containing dextran-behenic acid polymeric micelles (PM) were developed for the local delivery of niclosamide (NCL) to combat bacterial infections in the lungs of patients with cystic fibrosis. NCL loaded PM were prepared using dialysis method. Inhalable nanocomposites loaded with NCL were effectively prepared by co-spray drying the PM with inert carriers like mannitol and lactose. The physicochemical properties and in vitro deposition of the aerosolized nanocomposites were then evaluated. Additionally, the in vitro efficacy of the prepared formulations against Staphylococcus aureus was assessed using the agar well diffusion method. The optimized formulation exhibited a particle size of 333.67 ± 22.36 nm, a polydispersity index of 0.53 ± 0.08, a zeta potential of -2.90 ± 0.18 mV, an encapsulation efficiency of 52.07 ± 3.88%, a drug loading of 19.94 ± 1.49%, and a release efficiency of 54.04 ± 3.11%. Scanning electron microscopy also revealed that the nanomicelles were nearly spherical in shape. Both the NCL-loaded nanocomposite and PM demonstrated superior antibacterial efficacy at higher concentrations, as compared to free NCL and drug-free PM. It can be, therefore, concluded that dry powders embedding NCL-PM may serve as a viable alternative therapy for treating lung infections in patients with cystic fibrosis.
Metabolic and antioxidant parameters in the kidneys of rats treated with copaiba oil in cirrhosis induced by thioacetamide
This study evaluated the effects of copaiba oil on the kidneys of rats with cirrhosis induced by thioacetamide. Male Wistar rats were divided into four groups (n = 8), namely Control (C), Thioacetamide (TAA), Copaiba Oil (OC), and Thioacetamide + Copaiba Oil (TAA+OC). The biochemical and immunological analyses were performed, and results for the antioxidant enzymatic analysis revealed an increase in GST activity for TAA and TAA+OC compared to C. For GSH, higher values were observed in the TAA and TAA+OC groups compared to the C, but the latter differed from OC, such as TBARS. For Vit C, the TAA+OC group differed from the C and TAA and for glucose and lactate, lower values were observed for the TAA+OC group compared to the OC group. Cytokine concentrations showed the same profile with the TAA+OC group showing lower values compared to the C and OC groups. The data obtained do not show a clear positive effect of copaiba oil on kidney tissue when compared to the potential damage caused by thioacetamide. However, the groups that received either thioacetamide or copaiba oil alone maintained their basal levels, indicating that, at the doses used, these compounds did not negatively alter renal morphology.
DNA lipoplexes for gene therapy: a review
Gene therapy holds substantial promise for the treatment of a wide range of genetic and acquired diseases. Despite its potential, efficient and safe delivery of therapeutic genes into target cells remains a significant challenge. Lipoplexes, lipid-base formulations complexed with nucleic acids, have emerged as an attractive non-viral vector for gene delivery due to their ability to encapsulate and protect nucleic acids and facilitate their delivery into cells. This review focuses on the design, mechanism of action, and structure of lipoplexes for gene therapy and discusses the role of various lipids used in the formation of lipoplexes. Furthermore, we explore the application of lipoplexes in various disease models, cystic fibrosis, and cancers, highlighting recent advances. We conclude that while challenges remain, lipoplexes represent a promising strategy for safe and effective gene therapy.
Structural equation modeling to predict medication adherence in older people assisted by the public health system
With the increase in life expectancy, the demand for pharmaceutical care has risen, with the need to improve drug adherence. The study aimed to evaluate which variables in the literature most influence adherence. Two hundred twenty older patients from a specialty outpatient clinic were included. Potential drug interactions were identified using the Brief Medication Questionnaire (BMQ), and the Cumulative Illness Ratings Scales for Geriatrics and WHOQOL-Bref questionnaires were applied. The mean follow-up time at the outpatient clinic was 7.7 years, with 65% belonging to socioeconomic class C. The mean number of medications in use was 7, and 44% of the participants were taking psychotropic medication; 80.5% showed potential drug interaction. Cluster analysis revealed two groups: those motivated but concerned about their pharmacotherapy, and another with higher scores in drug effects and bothersome features, pain, and fear related to pharmacotherapy. The structural equation model showed that the BMQ total score was dependent on drug interaction and the public healthcare system's supply of medications. The concurrent use of multiple drugs and potential drug interaction favor non-adherence to medication, while adherence increases when the drug is provided by the health system, aspects that should be observed by the pharmaceutical attention to improve the treatment of older people.
Plant cells mediated biocatalytic reduction of aryl and heteroaryl carbonyl compounds: a comprehensive review
Biocatalysis is always considered as an efficient alternative for preparing a wide range of compounds with pharmaceutical/industrial importance. The immense popularity of biocatalysts is due to its striking features of being an environmentally benign, renewable and sustainable.In this present review, different methods of preparation of alcohols from their respective carbonyl compounds using different plant cells as biocatalysts are discussed. In addition, the importance of these alcohols in pharmaceutical industries and their methods of preparation in optically as well as chemically pure form are also discussed.
Gamma-terpinene counteracts in vivo dinitrochlorobenzene-induced atopic dermatitis in mice
Atopic dermatitis is a chronic skin condition characterized by impaired barrier function and underlying inflammation. Monoterpenes, a diverse class of secondary metabolites commonly found in essential oils, have been extensively documented for their potent anti-inflammatory properties. Therefore, this study evaluated the effects of gamma-terpinene (GT) on dinitrochlorobenzene (DNCB)-induced atopic dermatitis in a murine model. Macroscopic and histopathological analyses were conducted to assess skin lesions and ear edema, along with the assessment of serum immunoglobulin E (IgE), lactate dehydrogenase (LDH), and inflammatory cytokines (IL-4, IL-6, IL-1β, and TNF-α) in skin tissues. Histopathological analysis revealed a reduction in skin thickness, spongiosis, inflammatory cell infiltration, along with the presence of blisters and vesicles in both the epidermis and dermis. Additionally, cellular disarrangement and dermal fibrosis were observed. GT significantly decreased ear edema, serum IgE, and LDH levels, along with the expression of tissue IL-4, IL-6, IL-1β, and TNF-α. Therefore, the potential anti-inflammatory response induced by GT in atopic dermatitis suggests its potential for the development of GT-based therapies for chronic inflammatory skin disorders.
Activities, network pharmacology, potential mechanism against inflammation of a homogeneous polysaccharide MCP-1 from Mesona chinensis Benth
Inflammation is a condition in which the body’s immune system is compromised. Polysaccharides from Mesona chinensis Benth have been shown to repair the immune system and inhibit inflammation. This study aimed to investigate the activities, network pharmacology, and potential mechanisms of action against inflammation of a homogeneous polysaccharide, MCP-1, from M. chinensis. MCP-1 was isolated and purified using water extraction, alcohol precipitation, the Sevag method, and column chromatography. The molecular weight of MCP-1 was determined to be 70.9kDa. The polysaccharide composition included glucose (39.05%), arabinose (18.31%), galactose (14.80%), galacturonic acid (13.98%), xylose (7.42%), mannose (4.14%), and glucuronic acid (2.30%). MCP-1 showed strong inhibitory effects on the release of NO, IL-6, and TNF-α (30.79 ± 4.13%, 30.51 ± 3.25%, and 37.25 ± 3.57%, respectively). A total of 169 targets were identified based on the monosaccharide structures of MCP-1, with 9 targets associated with inflammation, including TLR4, STAT3, MMP9, COL18A1, TLR9, ABCB1, PPARA, MMP2, and NR1H4. The principal targets for anti-inflammatory therapies were associated with various signaling pathways involved in cancer and immune responses. Molecular docking experiments revealed that MCP-1 exhibited a high binding affinity for MMP2.
Medical abortion within the Brazilian context: analyzing potential impacts of adopting a MifeMiso regimen
In Brazil, when not criminalized, premature interruption of pregnancy may be performed through surgical abortion procedures (SAP) or medical abortion (MA). In the latter case, misoprostol monotherapy is the only available option, although the MifeMiso combination, which entails misoprostol administration after pretreatment with mifepristone, is the World Health Organization’s (WHO) preferred method. Here, we provide a state-of-the-art literature review, an evaluation of Brazilian clinical protocols, and a data analysis methodology exemplifying the impacts of adopting MifeMiso over misoprostol-only. The combination stands out for its superior efficacy, acceptability, and cost-effectiveness. Our findings show that the Brazilian technical standard could be improved, and that it would be valuable to have mifepristone approved for MA in the country. While legalization of abortion seems distant for Brazil, discussing all aspects of abortion is crucial for proper management of health resources, since the health system already bears the costs of illegal abortion.
Yacon-kefir beverage: a symbiotic product with improved antioxidant properties and no toxic effects
The aim of the present study was to obtain a symbiotic drink of a non-dairy matrix based on yacon juice fermented by kefir grains, biomonitored by antioxidant activity and pH value. A Box-Behnken experimental design was carried out to evaluate the effects of the concentrations of yacon juice and kefir grains, as well as of the fermentation temperature, on the antioxidant activity and pH. Thus, it was possible to define the optimal concentrations and temperature for the production of the drink with the best profile. Subsequently, in vitro analyses were performed to evaluate the physical chemical and microbiological characteristics of the drink, in addition to the in vivo assay using the experimental model Caenorhabditis elegans to assess a possible degree of acute toxicity. The results showed that the drink made with 82.7% yacon juice, fermented with 2% kefir grains at a temperature of 35ºC presented antioxidant potential, increased phenolic compounds, adequate physical-chemical characteristics and chemical composition, and the presence of probiotic microorganisms, in addition to not presenting acute toxicity in vivo.