Brazilian Journal of Pharmaceutical Sciences
The Brazilian Journal of Pharmaceutical Sciences publishes manuscripts that significantly contribute to knowledge in all areas of Pharmaceutical Sciences. Submissions: Brazilian Journal of Pharmaceutical Sciences - BJPS www.scielo.br/bjps
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
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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
Copyright (c) 2026 Brazilian Journal of Pharmaceutical Sciences https://creativecommons.org/licenses/by/4.0/
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.
Co-administration of paclitaxel and cisplatin liposomal improves efficacy and reduces toxicity of chemotherapy agents in murine breast cancer model
Paclitaxel (PTX) and cisplatin (CDDP) are potent cytotoxic drugs that target distinct intracellular pathways employed together for breast cancer therapy. While studies indicate enhanced treatment efficacy with drug combinations, the concomitant rise in adverse effects remains a concern. This study assessed the potential of co-administration of these drugs encapsulated into pH-sensitive liposomes (SpHL) against a murine triple-negative breast cancer model. The cytotoxicity studies revealed a concentration-dependent relationship between drug concentration and cell viability for both drugs. The combination effect of free drugs at IC50 and IC50 x2 showed an additive effect, while co-treatment with SpHL-PTX:SpHL-CDDP at IC50 x4 (1:3 molar ratio) displayed strong synergism (CI = 0.52). Other combinations exhibited antagonism (CI > 2.0). In vivo studies were performed at PTX:CDDP 1:3 molar ratio in two regimen protocols: single or dual dose protocol, resulting in different cumulative doses. Tumor growth was significantly decreased when two doses of free or encapsulated drugs were used compared to single-dose administration. Notably, encapsulated dual-dose treatments demonstrated enhanced antitumor efficacy, diminished systemic toxicity, and zero mortality. In conclusion, our study underscores the promising potential of co-administering encapsulated drugs into SpHL, highlighting their superior efficacy and reduced toxicity in breast cancer treatment compared to free drugs.
ERRATUM - Pre-treatment of the beta3-adrenergic receptor agonist BRL37344 reduces in vivo myocardial ischemia/reperfusion injury by improving AMPK and SIRT1 activity and by suppressing mTOR and p70S6K signaling pathways
Article: “Pre-treatment of the beta3-adrenergic receptor agonist BRL37344 reduces in vivo myocardial ischemia/reperfusion injury by improving AMPK and SIRT1 activity and by suppressing mTOR and p70S6K signaling pathways”, Authors: Dilan AŞKIN ÖZEK, Elif ONAT, Kazım ŞAHİN, Mehmet TUZCU, Merve Yılmaz BOZOĞLAN, Engin ŞAHNA, published in the Brazilian Journal of Pharmaceutical Sciences, vol 59: 1–7, 2023. DOI: https://doi.org/10.1590/s2175-97902023e23002. The authors would like to correct an error identified in Figure 2 of the published article. During the preparation of the figure, an inadvertent error occurred in the assembly of the western blot band images. Specifically, incorrect band images were placed in the panels for SIRT1 and p70S6K during figure construction. Importantly, the quantitative graphs presented in Figure 2 were generated from densitometric analyses of the correct original western blot data. The original raw data and unprocessed band images, including files with verifiable original creation dates, have previously been provided to the editorial office for transparency. Therefore, the graphical results accurately reflect the underlying experimental findings. This error is limited to the visual placement of representative band images and does not affect the quantitative analyses, scientific results, or the conclusions of the study. The corrected version of Figure 2 is provided below, following the original version. The authors apologize for this error and any inconvenience caused.
Designing a Humanized Immunotoxin Based on Gelonin Against HER2+ Breast Cancer: An In-Silico Study
Recombinant immunotoxins (RITs) are considered tumor-specific therapeutics because their variable antibody fragment can specifically bind to target cells, and their engineered toxin fragment specifically kills cancerous cells upon internalization. Human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor that is overexpressed in breast cancer (BC) patients and can be used for targeted therapies in the form of immunotoxins. The current study aimed to develop pertuzumab gelonin as a targeted immunotoxin for HER2-positive breast cancer cells using bioinformatics methods and to analyze its properties in silico. The Fab light and heavy chain of pertuzumab were linked to gelonin's ribosome-inactivating region (RIP) region. The amino acid sequence of the antibody chains was obtained from the Protein Data Bank Server (PDB), and the sequence of the RIP region of gelonin was obtained from the National Center for Biotechnology Information (NCBI). The immunotoxin's physicochemical properties, secondary, tertiary, and 3D structure, mRNA folding, allergenicity, solubility, and antigenicity were predicted from online servers, and protein-protein docking was also performed. The immunotoxin is stable, non-allergenic, and binds to HER2 receptors with high affinity. Based on our findings, it can be a good targeted therapy for HER2 breast cancer.
Evaluation of adherence to tenofovir treatment by hiv patients using drug concentrations in urine and standardized questionnaires
Adherence to tenofovir-based antiretroviral therapy is crucial for treatment success. In this study, we evaluated tenofovir urine concentrations in a cohort of patients that answered standardized adherence questionnaires Morisky-Green and Brief Medication Questionnaire (BMQ). Adherence evaluations were related to the patients’ viral load. Among the 72 patients who completed the questionnaires, 70 provided urine samples, and 88.6% of them had an undetectable viral load. Among the patients who provided urine samples and completed the Morisky-Green questionnaire, 45.7% were categorized as having high adherence, 54.3% as medium adherence, and 2.9% as low adherence. Utilizing a ROC curve (area under the curve of 0.864, CI 95% 0.757-0.971), a tenofovir urinary concentration of 6288.5 ng/mL was established as the cutoff value to predict high adherence according to the BMQ. This cutoff demonstrated a sensitivity of 93% and specificity of 72% in predicting high adherence according to the BMQ, with 73.5% of patients enrolled in the study categorized as having high adherence. When comparing adherence levels determined by the BMQ and urinary concentration, a moderate kappa index was observed (0.677, p<0.01). The results suggest that urine tenofovir concentration measurement as a feasible and efficient strategy to monitor adherence during HIV treatment with this drug.
Copyright (c) 2025 Brazilian Journal of Pharmaceutical Sciences https://creativecommons.org/licenses/by/4.0/
Vancomycin dosing nomograms as a tool to improve antibiotic use: a scoping review
This scoping review aimed to summarize studies that developed vancomycin dosing nomograms. A search was performed in MEDLINE, Embase, Scopus, LILACS, and Google Scholar for studies published from January 2009 until January 2014. Two authors performed the study selection and data extraction. Disagreements were resolved by the third author. Forty-three studies were included. Most of them were conducted in the U.S. (48.8%), developed for the adult population (81.4%), specifically for critically ill patients (39.7%), used population data as a method to create the nomogram (67.5%), considered the serum trough concentration as the pharmacodynamic target for developing the dosing nomogram (83.7%), chose intermittent infusion (76.8%) and recommended loading doses administration in their dosing nomogram (65.1%). Twenty-eight studies evaluated the dosing nomogram; 19 (67.8%) achieved optimal vancomycin serum levels. However, most studies were observational designs, with small sample sizes and few nomograms developed based on AUC guided dosing. Moreover, data on the clinical and microbiological outcomes of the patients enrolled in the studies are lacking. Vancomycin dosing nomograms were shown to be a valuable tool to guide the achievement of the PK/PD target, mainly in Middle-Income Countries. More robust methods for the development and evaluation of vancomycin dosing nomograms should be applied and associated with vancomycin TDM.
Copyright (c) 2025 Brazilian Journal of Pharmaceutical Sciences https://creativecommons.org/licenses/by/4.0
Validation of a chromatographic method for α-phellandrene quantification in skin permeation studies
Alpha-phellandrene (α-PHE), a cyclic monoterpene abundant in volatile oils, has anti-inflammatory and healing properties. A cutaneous formulation using this bioactive could provide benefits in wound healing. However, a simple method that quantifies α-PHE in the skin is still required. Thus, the study aims to develop and validate a high-performance liquid chromatographic (HPLC-UV) method to quantify α-PHE extracted from the skin. The method uses a reversed-phase C18 column (15 cm × 4.6 mm, 5 μm) and a mobile phase consisting of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) flowing at 0.5 mL/min. The phase concentration (A/B %) along the 40-min run time varied as described: 15/85 (0.01–10 min), 0/100 (10.1–20 min), and 15/85 (20.1–40 min). α-PHE was detected at 263 nm. The method was selective against skin and formulation interferents, linear (r = 0.9995) in a concentration range of 0.5–15.0 μg/mL, precise with an overall variation coefficient lower than 5.5%, accurately achieving recovery from the skin within 92–102%, and sensitive for the proposed application (detection limit = 0.05 µg/mL, quantification limit = 0.14 μg/mL). Finally, the validated method was tested in a skin penetration study, attesting to its success in developing topical formulations containing α-PHE.
Topical formulation with ascorbyl tetraisopalmitate and synthetic tripeptide, combined with facial muscle exercises
Facial aging involves natural processes such as bone resorption, subcutaneous volume loss, ligament laxity, and skin flaccidity. Currently, many aesthetic treatments are used to attenuate or delay the signs of facial aging, including facial exercises. They intend to improve skin elasticity, muscle tone, collagen production, and add (or reduce) volume of specific regions of the face. This study evaluated the effectiveness of a cosmetic formulation with ascorbyl tetraisopalmitate and synthetic tripeptide, combined with facial muscle exercises, in 43 healthy women aged between 30 and 65 years old. Participants were randomized into 3 groups: cosmetic formulation, cosmetic formulation + facial exercises, and facial exercises only. Instrumental measurements and self-assessment questionnaires were used to evaluate skin parameters. Significant improvement in skin firmness and elasticity were observed and attributed to the use of the cosmetic formulation. Additionally, participants noticed qualitative improvements in the appearance of their overall skin and wrinkles. High satisfaction scores were recorded for the facial exercise device and the formulation applied in the study. In conclusion, the cosmetic formulation had a positive impact on skin health, and the association of facial exercises, within time and conditions of this study, did not significantly increase the results caused by the formulation.
Therapeutic potential of Momordica charantia L. Extracts on melanoma cells revealed by metabolomic profiling
This manuscript evaluates the influence of Momordica charantia L. fruit and seed extracts on B16-F10 melanoma cell lines. The study was concerned with the application of these extracts to the cell lines and subsequent, in comparison to a control group, examination of the resultant metabolite profiles. A comprehensive analysis of metabolites was conducted by employing state-of-the-art Q-TOF LC/MS methodology in which the mature fruit and seed methanol extracts of M. charantia were prepared. The extracts were applied to B16-F10 melanoma cell lines for 48 and 72 hours, after which the cell lines obtained were analyzed using a Q-TOF LC/MS using a C18 column (Poroshell HPH-C18,2.1x100mm,2.7 µm) with a gradient elution program. The raw data obtained was examined using various data analysis methods, and the identified metabolites were reviewed to investigate the potential relationship between the phytochemical components of extract and potential anticancer activity. Certain changes (the levels of L-carnitine, arginine, N-methyltryptamine, sphingosine, prostoglandin, tryptophan and urocanic acid) at the metabolome level were related to potential anti cancer activity and antioxidant activity. This study demonstrated that the fruit and seed extracts of M. charantia induced metabolic changes, associated with anticancer activity, on melanoma cells through distinct pathways.
The aqueous extract of Cissus verticillata leaves prevents diabetic allodynia in type 1 and type 2 diabetic mouse models regardless of glycemic control
Cissus verticillata (L.) Nicolson & C.E. Jarvis, popularly known as “plant-insulin,” is used in Brazilian popular medicine for various conditions, including diabetes. Despite its usage, scientific research on its effects remains limited. In this regard, this study aimed to explore the potential anti-diabetic effects of C. verticillata’s aqueous extract (AECv) in mouse models of type 1 diabetes (T1D) and type 2 diabetes (T2D). T1D was induced in Swiss mice via daily intraperitoneal administration of 50 mg/ kg streptozotocin (STZ) for five days. Mice were then treated orally with saline or AECv (30 mg/kg/ day or 300 mg/kg/day) for three weeks. After 18 days, behavioral tests were conducted, and glucose measurements were taken. To mimic T2D-like conditions, mice were fed standard rodent chow (SD) or a high-fat, high-fructose diet (western diet, WD) for 15 days and then received daily treatment with vehicle or AECv (300 mg/kg/day) for 21 days. Behavioral tests and a glucose tolerance test were then performed. AECv did not improve STZ- and WD-induced glucose impairments or anxiogenic like behavior but significantly alleviated mechanical allodynia in both models. While AECv lacked hypoglycemic, anxiolytic, or antidepressant effects, it demonstrated the potential to enhance the pain sensitivity threshold.
Technical concerns on the subdivision of multilayer tablets
Multilayer tablets are gaining popularity for combining active pharmaceutical ingredients in a single dosage unit. However, the need to personalize drug treatment frequently demands the subdivision of such dosage forms. This study aimed to evaluate the performance of commercial multilayer tablets from different geographic origins for subdivision. An analysis of morphology, dimensions, mechanical resistance, and mass measurements of the halves after subdivision by a tablet splitter was performed, as well as an analysis of the adhesion layers. The tablets failed to meet acceptable standards for mass variation (more than 10 % in over 60 % of the samples), mass loss, and friability (more than 3.0 and 1.5 % in half of the samples, respectively). Furthermore, most of the tablets had exhibited layer separation or weakening after the subdivision, resulting in a marked decrease in fracture force to values below 10 N. Several factors, including matrix heterogeneity and high thickness, may contribute to these results. Delamination in multilayer tablets represents a significant quality issue that can compromise their therapeutic utility. Given such a scenario, the subdivision of multilayer tablets should be avoided until developers implement appropriate strategies, ensuring safe conditions for the user.
Synthesis and activity evaluation of new second-generation santacruzamate a analogs against breast cancer cells
A series of second-generation compounds analogous to Santacruzamate A were designed, synthesized, and evaluated for their selective cytotoxic activity against the breast cancer cell line MDA-MB-231 (ATCC HTB-26). Compound 7 demonstrated the highest cytotoxicity and selectivity among the tested compounds, with an IC50 value of 8.30 μM, comparable to those of the positive controls cisplatin (8.46 μM) and etoposide (12 μM). In silico studies identified histone deacetylase 8 (HDAC8) as a potential target of compound 7, supporting its role as an HDAC inhibitor. Experimental data further confirmed the pro-apoptotic activity of compound 7, as it significantly increased caspase-3 and caspase-9 activities, along with TP53 and BAK expression compared to the untreated group. These findings indicate that compound 7 induces apoptotic cell death in tumor cells through the intrinsic mitochondrial pathway. This study highlights compound 7 as a promising candidate for further exploration as a selective anticancer agent targeting breast cancer cells.
Safety profile of Matricaria Chamomilla: insights from zebrafish embryo development toxicity testing
In an alternative medicinal system, Matricaria chamomilla is used for various conditions like inflammation, higher cholesterol, wounds, diabetes and pregnancy-related issues. However, there is contradiction about the use of Matricaria chamomilla at the time of pregnancy. Therefore, the present study is designed to investigate the embryotoxic and developmental effects of Matricaria chamomilla using zebrafish embryos as a model. Matricaria chamomilla's chemical profiling was done using GC-MS/MS analysis. Fertilized embryos were selected and exposed to 0.1% vehicle (alcohol) and test medicine Matricaria chamomilla (mother tincture, 6C and 30C) for 96 hrs. Normal control group embryo exposed to embryo media. All the embryos were observed for mortality, hatching, morphological parameters and heart rate till 96 hours. GC-MS/MS analysis revealed 80 phytochemical compounds in hydro-alcoholic extract of Matricaria chamomilla. It exerted a mild effect on hatching rate and showed mortality than any other group. Whereas, after the exposure of Matricaria chamomilla-6C and 30C, there were no changes observed in all the parameters. Overall, the result reveals that Matricaria chamomilla-6C and 30C (at high dilution) is found safe and indicated its safety at the time of pregnancy. However, further validation in higher animal models is recommended for proper clinical correlation.
RPLC method development and validation for the quantitative determination of phenytoin and valproic acid in tablet formulations
In this study, the reverse phase liquid chromatography (RPLC) method was preferred to determine the chromatographic behavior of phenytoin and valproic acid, the active ingredients of antiepileptic drugs. The optimization of the developed method was based on the capacity factor values of studied compounds in water-organic solvent mixtures varying in constant mobile phase pH value and the organic solvent concentration in the mobile phase where the compounds were analyzed. At constant pH, phenytoin was analyzed in acetonitrile-water binary mixtures containing 30-40% (v/v) acetonitrile, and valproic acid was analyzed in methanol-water binary mixtures containing 10-20% (v/v) methanol at 37oC. Kinetex EVO C18 Core-Shell (250x4,6mm I.D., 5µm) and Pinnacle DB Cyano (250 x 4,6 mm I.D., 5µm) columns were preferred for the quantitative determination of the compounds. Under all conditions mentioned in the method section, excellent linearity (r>0.99) was obtained in the concentration range of 10-40 μg/mL for phenytoin and 200-600 μg/mL for valproic acid. The recovery value of the method was calculated as 98.48% and 99.40% for phenytoin and valproic acid, respectively. In this study, an analytical procedure suitable for routine use was developed, and the method was validated for the determination of the amount of studied compounds in pharmaceutical dosage forms.
Rosmarinic acid: insights into analytical, pharmacological & pharmaceutical aspects
Rosmarinic acid is an indigenous antioxidant molecule derived from a variety of widely available herbal plants. This molecule exhibits a diverse array of pharmacological properties. Recently, there has been an increasing interest in the importance of its effects and its possible use as a natural antioxidant in processed foods. It is a naturally-occurring hydroxylated compound that is commonly found in species. The escalating emergence of antimicrobial resistance and the detrimental repercussions resulting from the excessive utilization of antibiotics are generating a need for novel antimicrobial therapies. Researchers are currently investigating natural compounds as a promising option in this context. Medicinal plants possess a substantial quantity of rosmarinic acid. It is widely used as a spice in various cuisines and is highly regarded in traditional medicine for its healing properties. Rosemary contains significant amounts of powerful antioxidant chemicals, such as phenolic diterpenes, flavonoids, and phenolic. This review aims to analyze the relationship between the structure and activity of Rosmarinic acid, as well as its chemistry, sources, biotechnological production, and neuroprotective effect. Additionally, it will focus on the nano formulation and commercialized formulations of Rosmarinic acid.