Stress, anxiety and depression in dental students: Impact of severe acute respiratory syndrome-coronavirus 2 pandemic.

INTRODUCTION: With the emergence of COVID-19, dental medicine students were faced with a new reality, as a modification of the learning methods in Dentistry colleges happened. The aim of this study was to characterise the possible effects of Covid-19 pandemic in terms of anxiety, depression, and stress among students of dentistry. MATHERIALS AND METHODS: This cross-sectional study was conducted between October 2020 and May 2021. A total of 1115 participants from a total of approximately 3000 students from the seven university institutions that teach the master's degree in dentistry in Portugal, agreed to participate. An online self-reported questionnaire was applied through Google Forms® platform. The questionnaire was divided in three sections: the students' sociodemographic characterisation, pedagogical aspects, and questions about anxiety, depression, and stress using the Depression, Anxiety, and Stress-21 Scale. RESULTS: Normal levels of anxiety, depression, and stress, were found in 41%, 36.7%, and 22.7% of the participants, respectively. Being female was the most significant and strong predictor of anxiety and stress, and for depression, not feeling fulfilled in the course they were in was the most significant variable. CONCLUSION: The participants presented high values of anxiety, depression, and stress, during the pandemic state. Gender and not feeling fulfilled in the course were important predictors.

Influence of in vitro neuronal membranes on the anti-amyloidogenic activity of gallic acid: Implication for the therapy of Alzheimer's disease.

Molecules inhibiting the amyloid beta (Aß) peptide aggregation and/or disaggregating mature fibrils are a promising approach for the Alzheimer's disease (AD) therapy, as the Aß fibrillation is one of the key triggers of the disease. Gallic acid (GA) is a phenolic acid with anti-amyloidogenic activity against Aß in buffered solutions. However, there is still no evidence of these properties in vivo. Given the rate of failures of AD drug development, there is a huge demand of replicating the in vivo environment in in vitro studies, thus allowing to stop earlier the study of molecules with no effect in vivo. Thus, this study aims to evaluate the effect of in vitro neuronal membranes on the GA's ability in preventing Aß1-42 aggregation and disrupting preformed fibrils. To this end, liposomes were employed to mimic the cell membrane environment. The results reveal that the lipid membranes did not affect the GA's ability in inhibiting Aß1-42 fibrillation. However, in vitro neuronal membranes modulate the GA-induced Aß fibrils disaggregation, which may be related with the moderate affinity of the compound for the lipid membrane. Even so, GA presented strong anti-amyloidogenic properties in the cell membrane-like environment. This work highlights the promising value of GA on preventing and treating AD, thus justifying its study in animal models.

The Role of Amyloid ß-Biomembrane Interactions in the Pathogenesis of Alzheimer's Disease: Insights from Liposomes as Membrane Models.

The aggregation and deposition of amyloid ß (Aß) peptide onto neuronal cells, with consequent cellular membrane perturbation, are central to the pathogenesis of Alzheimer's disease (AD). Substantial evidence reveals that biological membranes play a key role in this process. Thus, elucidating the mechanisms by which Aß interacts with biomembranes and becomes neurotoxic is fundamental to developing effective therapies for this devastating progressive disease. However, the structural basis behind such interactions is not fully understood, largely due to the complexity of natural membranes. In this context, lipid biomembrane models provide a simplified way to mimic the characteristics and composition of membranes. Aß-biomembrane interactions have been extensively investigated applying artificial membrane models to elucidate the molecular mechanisms underlying the AD pathogenesis. This review summarizes the latest findings on this field using liposomes as biomembrane model, as they are considered the most promising 3D model. The current challenges and future directions are discussed.

Sex estimation using the mandibular canine index components.

The mandibular canine index (MCI) has been described as a suitable methodology for sex estimation in forensic scenarios but there are contradictory reports about its accuracy. Moreover, the two mandibular canine teeth must be available, which is not always a viable option. The aim of this study was to strip the MCI by analyzing the MCI itself and its components, in order to optimize its use for sex estimation. The mesiodistal dimensions of the mandibular canine crown and the mandibular canine arch width were measured in a sample of 120 cast models. Five predictor variables were considered in this study: the standard MCI, a variation of the MCI using the left canine, and MCI components (MD43, MD33 and D33-43). Multivariate binary logistic regression was performed using stepwise forward approach to select the most statistical relevant variables on the probability of a cast being from a female. The estimated probability was then analyzed with respect to performance in sex classification (ROC analysis and optimal cut-offs accuracy) and compared with the performance of the univariate variables. MCI43 and MCI33 presented the lowest performance (64.2% and 63.3% respectively), and the highest overall accuracy was attained using the MD43 and MD33 (85.8% in both cases). The multivariate logistic model obtained (using MD43 and MD33) exhibited the same accuracy as the logistic model based solely on MD43 (85.8%). Our results suggest that MD43 should be used instead of MCI for sex estimation.

Chronology of mineralization of the permanent mandibular second molar teeth and forensic age estimation.

Forensic age estimation frequently relies upon the chronology of mineralization of the third molar teeth. However, even when present, third molar teeth cannot always be used for estimating age in people who are classified as minors. Seconds molars develop earlier and in a more predictable way, and therefore are often more reliable for age estimation in this age group. This study aims to contribute to forensic age estimation using an age threshold of 14-years, studying the stages of development of permanent mandibular second molar teeth mineralization. 367 orthopantograms of a Portuguese population group, aged between 3 and 19 years, were studied. The stages of mineralization of mandibular permanent second molar teeth were studied following the classification stages proposed by Demirjian et al. Stage descriptive analysis was performed, and associations between age and stage were studied. A logistic regression to determine age over 14 years, using maturation stages and sex as a predictive variables, was made. A second sample was used for testing the model. The significance level was set at 5%. The model correctly classified 92.0% of cases overall. The equation was tested in the second sample, and the results showed that there were no statistical significant differences between the binary real age (i.e. age < 14 and age ≥ 14 years) and the estimated age (p = 0.109). The developed model is useful for age estimation using 14-years as a threshold. However, stage maturation analyses showed that stage F, in males, and stages G and H, in both sexes, lead to an estimated age with significant statistical differences from chronological age.

Structural characterization of functionalized gold nanoparticles for drug delivery in cancer therapy: a NMR based approach.

In the present paper, we report results from a study of the structure and physicochemical properties of gold nanoparticles modified with poly(ethylene glycol) (PEG) designed for the drug delivery of the proteasome inhibitor Bortezomib (BTZ) in cancer therapy. A number of advanced analytical techniques were used to define important physicochemical characteristics such as composition, structure, surface properties, particle size and morphology. A new approach based on detailed NMR studies was employed to define specific intermolecular interactions and mechanisms of drug immobilization and location into surface modified gold nanoparticles (AuNPs). Particularly important information was gained from analysis of NMR spectroscopic parameters such as the spectral line shape, translation diffusion, the nuclear Overhauser effect (NOE) and spin-lattice relaxation (T1). The results confirmed the coexistence of two different types of BTZ inclusion into polyethylene glycol coated gold nanoparticles: (i) association with the polymer chains by weak H-bonds and/or dipole-charge interactions and (ii) adsorption on the surface of the gold nanoparticles. The results allowed for determination of the overall structure of Bortezomib loaded PEG coated AuNPs, which is related to the therapeutic drug efficacy and activity in the treatment of cancer.

Tool to measure workload of health professionals in Primary Health Care: development and validation. / Instrumento de medida de carga de trabalho dos profissionais de Saúde na Atenção Primária: desenvolvimento e validação.

Objective To develop and validate an instrument that addresses the interventions/activities carried out by the family health team as reference for staff planning. Method Methodological research developed in stages: instrument development, content validation, and pilot test in three units located in the southeastern region of Brazil. Results 39 interventions were validated in a single instrument to measure workload for clinician, dental surgeon, oral health technician/assistant, nurse, nurse assistant, and community health agent. In the pilot test, the instrument contained 100% of the interventions observed and the observers reached 93.7% agreement. Conclusion The proposed instrument is an innovating tool because of its configuration for health team and supports staff planning in primary health care.

Mini-review: Antimicrobial peptides and enzymes as promising candidates to functionalize biomaterial surfaces.

Biomaterial-associated infections remain a serious concern in modern healthcare. The development of materials that can resist or prevent bacterial attachment constitutes a promising approach to dealing with this problem. Antimicrobial peptides (AMPs) and enzymes have been recognized as promising candidates for the new generation of antimicrobial surfaces. AMPs have been the focus of great interest in recent years owing to a low propensity for developing bacterial resistance, broad-spectrum activity, high efficacy at very low concentrations, target specificity, and synergistic action with classical antibiotics. Biofilm-dispersing enzymes have been shown to inhibit biofilm formation, detach established biofilm, and increase biofilm susceptibility to other antimicrobials. This review critically examines the potential of these protein-like compounds for developing antibacterial coatings by reporting their immobilization into different substrata using different immobilization strategies.

Caries and oral health related behaviours among homeless adults from Porto, Portugal.

PURPOSE: To describe caries prevalence and oral-health-related behaviours in a sample of homeless adults from the city of Porto, Portugal. MATERIALS AND METHODS: Subjects attending any of two temporary shelters or two institutions that provide meal programmes were consecutively invited (n = 196); 42 (21.4%) refused to participate. Trained interviewers applied a structured questionnaire to obtain sociodemographic, behavioural, health and oral health status data. An oral examination was conducted to evaluate the past and present history of caries (Decayed Missing Filled Teeth [DMFT] index) and the presence of oral lesions. Those classified as houseless were considered for the present analysis (n = 141). The association between homelessness, sociodemographic and behavioural characteristics and oral health indexes was quantified through crude ß coefficients and ß coefficients adjusted for age, gender, education, nationality and duration of homelessness, as well as the respective 95% confidence intervals (CI). RESULTS: The median age of the participants was 45 years, most were male (86.3%), reported having less than a 9th grade education (80.1%) and were unemployed (82.1%). The median duration of homelessness was 24 months. The mean (SD) DMFT index, number of decayed, lost and filled teeth were 12.8 (7.9), 4.2 (4.4), 8.0 (7.6) and 0.6 (1.9), respectively. Older subjects and those homeless for longer periods presented higher DMFT index scores (ß = 3.4, 95% CI: 0.0 to 6.8) and higher number of decayed teeth (ß = 2.8, 95% CI: 0.4 to 5.2). Filled teeth were more frequent among the more educated (>9 vs ≤4 years: ß = 1.6, 95% CI: 0.7 to 2.6). CONCLUSIONS: This population of homeless subjects showed poor oral health, particularly with respect to caries and missing teeth, resulting in high oral treatment needs.

Chitosan-PLGA mucoadhesive nanoparticles for gemcitabine repurposing for glioblastoma therapy.

Glioblastoma (GBM) is a highly deadly brain tumor that does not respond satisfactorily to conventional treatment. The non-alkylating agent gemcitabine (GEM) has been proposed for treating GBM. It can overcome MGMT protein-mediated resistance, a major limitation of conventional therapy with the alkylating agent temozolomide (TMZ). However, GEM's high systemic toxicity and poor permeability across the blood-brain barrier (BBB) pose significant challenges for its delivery to the brain. Thus, mucoadhesive poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) coated with chitosan (CH), suitable for intranasal GEM delivery, were proposed in this work. A central composite design (CCD) was implemented for NPs optimization, and NPs with appropriate characteristics for intranasal administration were obtained. in vitro studies revealed that the NPs possess excellent mucoadhesive properties and the ability to selectively release GEM in the simulated tumor tissue environment. in vitro studies using two human GBM cell lines (U215 and T98G) revealed the NPs' ability to promote GEM's antiproliferative activity to sensitize cells to the effect of TMZ. The findings of this work demonstrate that the developed CH-GEM-NPs are suitable delivery systems for GEM, both as a single therapy and as a chemosensitizer to the GBM gold standard therapy.

Spatial and Temporal Dynamics of Fecal Coliform and Associated with Suspended Solids and Water within Five Northern California Estuaries.

Fecal coliform and associated with suspended solids (SS) and water in five northern California estuaries were studied to document process influences and water quality monitoring biases affecting indicator bacteria concentrations. We collected and analyzed 2371 samples during 10 sampling events for the five studied estuaries. Concentrations during wet-season stormflow conditions were greater than during wet-season base flow and dry-season base flow conditions. Results also document concentration gradients across the length of the studied estuaries and with depth of sample collection. Highest concentrations were associated with shallow samples collected furthest inland. Corresponding decreases occurred the deeper and closer to the estuary mouth a sample was collected. Results also identify direct relationships of wind speed and discharge velocity and indirect relationship of tide stage to indicator bacteria concentrations. Bacteria associated with suspended solids (SS), after conversion to the same units of measurement (mass), were three orders of magnitude greater than in the water fraction. However, the mean proportion contributed by SS to composite water sample concentrations was 8% (SE 0.3) for fecal coliform and 7% (SE 0.3) for . Bacteria from the SS proportion is related to seasonality, tide stage, and discharge velocity that are consistent with mechanisms for entrainment, transport of SS, and reduced particle settling. These results are important for both managing and monitoring these systems by improving sample spatial and temporal context and corresponding bacteria concentration values across the freshwater-saltwater interface.

Caffeic acid loaded into engineered lipid nanoparticles for Alzheimer's disease therapy.

Alzheimer's disease (AD) is an incurable neurological illness and the leading cause of dementia, characterized by amyloid ß (Aß) fibril deposits. Caffeic acid (CA) has demonstrated potential value for AD therapy due to its anti-amyloidogenic, anti-inflammatory, and antioxidant properties. However, its chemical instability and limited bioavailability limit its therapeutic potential in vivo. Herein, liposomes loading CA were produced by distinct techniques. Taking advantage of the overexpression of transferrin (Tf) receptors in brain endothelial cells, Tf was conjugated to the liposomes' surface to direct the CA-loaded nanoparticles (NPs) to the blood-brain barrier (BBB). The optimized Tf-modified NPs exhibited a mean size of around 140 nm, a polydispersity index lower than 0.2, and a neutral surface charge, being appropriate for drug delivery. The Tf-functionalized liposomes showed suitable encapsulation efficiency and physical stability for at least 2 months. Furthermore, in simulated physiological settings, the NPs ensured the sustained release of CA for 8 days. The anti-amyloidogenic efficacy of the optimized drug delivery system (DDS) was investigated. The data show that CA-loaded Tf-functionalized liposomes are capable of preventing Aß aggregation and fibril formation, and disaggregating mature fibrils. Hence, the proposed brain-targeted DDS may be a potential strategy for preventing and treating AD. Future studies in animal models of AD will be valuable to validate the therapeutic efficacy of the optimized nanosystem.

Knowledge, attitudes, and practices of prenatal care practitioners regarding oral health in pregnancy-A systematic review.

BACKGROUND: Hormonal and behavioral changes during pregnancy may impact the oral health of women, which can influence the pregnancy course. Prenatal care practitioners (PCP) must be aware of this bidirectional relation in order to include an oral assessment in routine prenatal care. OBJECTIVES: To characterize the knowledge and attitudes of PCP regarding oral health in pregnant women. SEARCH STRATEGY: The search was carried out in PubMed, Web of Science, Lilacs, Scopus, and Embase on May 2022. SELECTION CRITERIA: Peer-reviewed cross-sectional studies published in English within the last 5 years that assessed the knowledge, attitudes, and practices of PCP towards oral health in pregnancy were selected. DATA COLLECTION AND ANALYSIS: Data were standardly extracted by the three reviewers from the selected articles and their bias was assessed. MAIN RESULTS: From a total of 996 articles, 24 were selected. Overall, most PCP have an adequate level of knowledge regarding the importance of oral health during pregnancy. Although several professionals reported referring their patients to a dentist, the attitudes and practices of the majority of PCP were still inadequate. CONCLUSIONS: PCP are aware of the importance of oral health during pregnancy but still lack translating this knowledge into clinical practice.

Engineered liposomes to deliver nucleic acid mimics in Escherichia coli.

Antisense oligonucleotides (ASOs) composed of nucleic acid mimics (NAMs) monomers are considered as potential novel therapeutic drugs against bacterial infections. However, bacterial envelopes are generally impermeable to naked oligonucleotides. Herein, liposomes loaded with NAMs-modified oligonucleotides (LipoNAMs) were evaluated to deliver ASOs in Escherichia coli. Specifically, we tested several surface modifications that included methoxyPEG conjugated to different lipid anchors or modification of the PEG distal ends with maleimide groups and antibodies. MethoxyPEG coated LipoNAMs showed low delivery efficiency for most bacteria, but maleimide-functionalized PEG LipoNAMs were able to deliver ASOs to nearly half of the bacterial population. Conjugation of antibodies to maleimide-functionalized PEG LipoNAMs increased 1.3-fold the delivery efficiency, enhancing the selectivity towards E. coli and biocompatibility. This work demonstrated for the first time that the coupling of antibodies to PEGylated liposomes can significantly improve the delivery of ASOs in E. coli, which might bring alternative routes for the treatment of bacterial infections in the future.

Platelet aggregation inhibitors from Bothrops alternatus snake venom.

Snake venoms are a complex mixture of proteins and peptides that can activate/inhibit platelet aggregation. Bothrops alternatus venom include three main families: metalloproteinases (SVMPs), serinoproteinases (SVSPs) and phospholipases A2 (PLA2s), among other minor components. In this work, we used inhibitor cocktails (containing Na2-EDTA, PMSF and/or pBPB) to investigate the effect of these three families and of baltergin (a PIII SVMP) on platelet aggregation by a turbidmetric method using a microplate reader. Cocktails 1 (active SVMPs) and 2 (active PLA2s) significantly reduced aggregation induced by ristocetin and collagen and by collagen and thrombin, respectively. Cocktail 3 (active SVSPs) showed a mild activation of aggregation, indicating the content of thrombin-like enzymes (TLEs) in this venom is low. Cocktail 4 (active minor components) displayed inhibitory effect with all agonists assayed (ristocetin, ADP, collagen and thrombin) but at higher IC50 values. Baltergin exhibited inhibitory effect when the catalytic domain was active for ristocetin-stimulated platelet aggregation and showed a non-enzymatic mechanism of inhibition when collagen was used as agonist. It was not able to disaggregate platelet thrombus. We conclude that B. alternatus venom is a source of natural inhibitors of platelet aggregation due to the action of SVMPs and PLA2s. Other minor components such as C-type lectins likely contribute to the antiplatelet effect. The interest in knowing the action of venom components on platelet function lies both in the understanding of the pathophysiology of snake bite envenomation and in their biotechnological application.

Impact of implant metal type and vancomycin prophylaxis on postoperative spine infection: an in-vivo study.

PURPOSE: To evaluate the effectiveness of vancomycin prophylaxis on spinal implant metal types. METHODS: 42 rabbits underwent posterior, single-level instrumentation at L5-L6 with stainless steel (n = 18), cobalt chrome (n = 12), or titanium (n = 12) wire. All implants were inoculated with 1 × 106 colony forming units (CFU) of methicillin-resistant S. Aureus (MRSA). In the intrawound vancomycin subgroup (n = 18, 6 from each metal type), 40 mg of vancomycin powder was placed in the wound. In the IV vancomycin subgroup (n = 6, all stainless steel), 15 mg/kg of IV vancomycin was given preoperatively. Local soft tissue and implants were harvested 1-week postoperatively and separately cultured. RESULTS: Intrawound vancomycin significantly reduced the rate of soft tissue infection (44.4% vs 100%) and implant infection (27.8% vs 100%) (p < 0.001). Within the intrawound vancomycin subgroup, cobalt chrome implants were associated with higher median soft tissue MRSA growth (130 CFU) than stainless steel (0 CFU) or titanium (0 CFU) (p = 0.02). Cobalt chrome implants were also more likely to develop soft tissue MRSA infection (83.3%) as compared to stainless steel (16.7%) or titanium (33.3%) (p = 0.04). Median soft tissue MRSA growth among stainless steel implants without prophylaxis, with IV vancomycin, and with vancomycin powder was 1.18 × 107, 195, and 0 CFU, respectively. The rate of soft tissue MRSA infection without prophylaxis, with IV vancomycin, and with vancomycin powder was 100, 66.7, and 16.7%, respectively (p = 0.015). CONCLUSION: Intrawound vancomycin is more effective than IV vancomycin and effectively reduces the risk of infection, but is less effective in cobalt chrome implants due to residual soft tissue infection.

The potential impact of delivery mode and breastfeeding on oral Candida species carriage in a population of young adults.

OBJECTIVES: In early life, children are exposed to microorganisms from maternal and environmental sources, which influence the development of their microbiome throughout life. Several studies have demonstrated the influence of the delivery mode and breastfeeding on the oral microbiome of children, mostly regarding bacterial colonization. However, their influence on the oral fungal carriage is still underexplored. This study aimed to assess the association of the delivery and feeding mode with the oral carriage of yeasts in adulthood. METHOD AND MATERIALS: Fungal oral carriage was evaluated by collecting unstimulated saliva in 185 healthy dental students (mean age of 21.51 ± 1.55 years old; 81.6% women). Yeast identification was performed by culture in ChromAgar Candida medium and sequencing of the 18S genes and ITS regions for determination of the species. Demographic and clinical data of each participant were recorded through questionnaires, and oral examinations were performed in a subgroup of participants (n = 49). RESULTS: Candida species were isolated in 37.5% of all participants. The prevalence of yeasts in the oral cavity was significantly higher in those who were born by vaginal delivery compared to those born by caesarean section (P = .035), whereas no statistically significant differences were observed regarding breastfeeding (P = .398). Low salivary flow rate and frequency of dental visits also were associated with oral yeast carriage (P < .05). CONCLUSION: The results suggest a possible impact of the type of delivery on fungal colonization, which is sustained throughout life due to oral health-related factors.

Biomaterials for Testicular Bioengineering: How far have we come and where do we have to go?

Traditional therapeutic interventions aim to restore male fertile potential or preserve sperm viability in severe cases, such as semen cryopreservation, testicular tissue, germ cell transplantation and testicular graft. However, these techniques demonstrate several methodological, clinical, and biological limitations, that impact in their results. In this scenario, reproductive medicine has sought biotechnological alternatives applied for infertility treatment, or to improve gamete preservation and thus increase reproductive rates in vitro and in vivo. One of the main approaches employed is the biomimetic testicular tissue reconstruction, which uses tissue-engineering principles and methodologies. This strategy pursues to mimic the testicular microenvironment, simulating physiological conditions. Such approach allows male gametes maintenance in culture or produce viable grafts that can be transplanted and restore reproductive functions. In this context, the application of several biomaterials have been proposed to be used in artificial biological systems. From synthetic polymers to decellularized matrixes, each biomaterial has advantages and disadvantages regarding its application in cell culture and tissue reconstruction. Therefore, the present review aims to list the progress that has been made and the continued challenges facing testicular regenerative medicine and the preservation of male reproductive capacity, based on the development of tissue bioengineering approaches for testicular tissue microenvironment reconstruction.

Transferrin-functionalized liposomes loaded with vitamin VB12 for Alzheimer's disease therapy.

Despite the efforts of the pharmaceutical and research sectors, Alzheimer's disease (AD) remains incurable, imposing the demand for new effective strategies. Vitamin B12 (VB12) has aroused interest due to its in vitro anti-amyloidogenic properties. However, the high molecular weight and hydrophilicity of VB12 are the main obstacles to its clinical application by hindering its passage through the blood-brain barrier (BBB). In recent years, drug delivery systems (DDSs) capable of transporting molecules across the BBB have gained attention for their effective brain delivery. In this work, VB12-loaded liposomes functionalized with transferrin (Tf) were produced, envisaging the dual-targeting of VB12 to the BBB and neuronal cells, due to the overexpression of Tf receptors in these cells. The produced liposomes presented sizes smaller than 200 nm, with low polydispersity and neutral zeta potential, being suitable for brain delivery. The nanoparticles exhibited an adequate encapsulation efficiency, a sustained release of VB12 for 9 days, and physical stability at storage conditions for up to 2 months. The developed nanosystem was capable of delaying the formation of Aß fibrils and disrupting mature fibrils, highlighting its great potential for the prevention and treatment of AD.

Transferrin-modified nanoparticles for targeted delivery of Asiatic acid to glioblastoma cells.

AIMS: Glioblastoma (GBM) is the most common and deadliest type of brain cancer, and the current therapeutic options are not curative, imposing the need for novel strategies. Asiatic acid (AA) is a natural compound and has been explored due to its anti-glioma activity and lower toxicity to healthy tissues compared with conventional chemotherapeutic agents. However, its poor water-solubility is an obstacle for clinical application. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were proposed in this work for Asiatic acid (AA) delivery. MAIN METHODS: A central composite design was implemented to optimize the NPs, and their surface was further modified with transferrin (Tf), for targeted delivery to GBM cells. The anti-glioma activity of the NPs was studied in vitro using human GBM cells and immortalized human astrocytes. KEY FINDINGS: The NPs exhibited a mean size smaller than 200 nm, with low polydispersity and negative zeta potential, indicating their suitability for brain tumor delivery. The NPs also exhibited high encapsulation efficiency and maintained a slow and controlled release of AA for 20 days. In vitro cell studies showed that NPs were able to maintain the anti-glioma activity of the natural compound and that the surface modification with Tf molecules was able to increase the cellular uptake in GBM cells, enhancing their selectivity and decreasing toxicity in healthy cells. SIGNIFICANCE: Overall, this work provided guidance for designing brain-targeting delivery systems of natural compounds.