Effective Mosquito Repellents: Myrcene- and Cymene-Loaded Nanohydrogels against Aedes aegypti.

Aedes mosquito-borne diseases remain a significant global health threat, necessitating effective control strategies. This study introduces monoterpenes-based nanohydrogels for potential use as repellents against Aedes aegypti, the primary dengue vector worldwide. We formulated hydrogels using cymene- and myrcene-based nanoemulsions with different polymers: chitosan, carboxymethylcellulose (CMC), and carbopol®. Our evaluations of rheological, texture, and bioadhesive properties identified CMC hydrogel as the most promising gelling agent for topical application, exhibiting sustained monoterpene release over 12 h with low skin permeation and high retention in the stratum corneum. Myrcene-loaded CMC hydrogel achieved a 57% feeding deterrence compared to 47% with cymene hydrogel in the mosquito membrane-feeding model. Molecular docking studies revealed interactions between myrcene and an essential amino acid (Ile116) in the Ae. aegypti odorant-binding protein 22 (AeOBP22), corroborating its higher repellent efficacy. These findings suggest that myrcene-loaded CMC hydrogels offer a promising, minimally invasive strategy for personal protection against Ae. aegypti and warrant further investigation to optimize monoterpene concentrations for vector control.

Cellulose from bacteria as a delivery system for improved treatment of infectious diseases: A review of updates and prospects.

Cellulose from bacteria is a high-purity biomaterial naturally produced by bacteria as part of their metabolic process. Although it inherently lacks antimicrobial activity, its modification with bioactive substances can significantly enhance its efficacy beyond that of the original compounds. This biomaterial features a unique ability to retain substantial quantities of liquids within its three-dimensional network, making it a prime candidate for biomedical applications. Versatile in its properties, it can be utilized across various industries. Previous research has highlighted its capacity to exhibit antimicrobial properties and to encapsulate nanostructured materials, thereby augmenting its antibacterial effectiveness. This review focuses on the use of cellulose from bacteria as a carrier for active compounds, specifically targeting antibacterial activity against drug-resistant strains. We explore its role in innovative bacterial cellulose-based systems, which present a promising solution for tackling bacterial resistance. This review aims to showcase the potential of bacterial cellulose in developing new devices and treatment strategies that address critical concerns in global health.

Formulation of a Novel Hesperetin-Loaded Nanoemulsion and Its Promising Effect on Osteogenesis.

Alternative therapies associating natural products and nanobiotechnology show new perspectives on controlled drug release. In this context, nanoemulsions (NEs) present promising results for their structural design and properties. Hesperetin (HT), a flavonoid mainly found in citrus fruits, presents highlighted bone benefits. In this context, we developed a hesperetin-loaded nanoemulsion (HT-NE) by sonication method and characterized it by dynamic light scattering, analyzing its encapsulation efficiency, and cumulative release. The biocompatibility in human osteoblasts Saos-2-like was evaluated by the cytotoxicity assay and IC50. Then, the effects of the HT-NE on osteogenesis were evaluated by the cellular proliferation, calcium nodule formation, bone regulators gene expression, collagen quantification, and alkaline phosphatase activity. The results showed that the formulation presented ideal values of droplet size, polydispersity index, and zeta potential, and the encapsulation efficiency was 74.07 ± 5.33%, showing a gradual and controlled release. Finally, HT-NE was shown to be biocompatible and increased cellular proliferation, and calcium nodule formation, regulated the expression of Runx2, ALPL, and TGF-ß genes, and increased the collagen formation and alkaline phosphatase activity. Therefore, the formulation of this NE encapsulated the HT appropriately, allowing the increasing of its effects on mechanisms to improve or accelerate the osteogenesis process.

Larvicidal properties of terpenoid-based nanoemulsions against the dengue vector Aedes aegypti L. and their potential toxicity against non-target organism.

The development of insecticide resistance in mosquitoes of public health importance has encouraged extensive research into innovative vector control methods. Terpenes are the largest among Plants Secondary Metabolites and have been increasingly studied for their potential as insecticidal control agents. Although promising, terpenes are insoluble in water, and they show low residual life which limits their application for vector control. In this study, we developed and evaluated the performances of terpenoid-based nanoemulsions (TNEs) containing myrcene and p-cymene against the dengue vector Aedes aegypti and investigated their potential toxicity against non-target organisms. Our results showed that myrcene and p-cymene showed moderate larvicidal activity against mosquito larvae compared to temephos an organophosphate widely used for mosquito control. However, we showed similar efficacy of TNEs against both susceptible and highly insecticide-resistant mosquitoes from French Guyana, hence suggesting an absence of cross-resistance with conventional insecticides. We also showed that TNEs remained effective for up to 45 days in laboratory conditions. The exposure of zebrafish to TNEs triggered behavioral changes in the fish at high doses but they did not alter the normal functioning of zebrafish organs, suggesting a good tolerability of non-target organisms to these molecules. Overall, this study provides new insights into the insecticidal properties and toxicity of terpenes and terpenoid-based formulations and confirms that TNE may offer interesting prospects for mosquito control as part of integrated vector management.

Development and characterization of potential larvicidal nanoemulsions against Aedes aegypti.

Plant-based insecticides offer advantages such as negligible residual effects, reduced risks to both humans and the environment, and immunity to resistance issues that plague conventional chemicals. However, the practical use of monoterpenes in insect control has been hampered by challenges including their poor solubility and stability in aqueous environments. In recent years, the application of nanotechnology-based formulations, specifically nanoemulsions, has emerged as a prospective strategy to surmount these obstacles. In this study, we developed and characterized nanoemulsions based on cymene and myrcene and assessed their toxicity both in vitro using human keratinocytes (HaCAT) cells and in an in vivo model involving Galleria mellonella larvae. Additionally, we investigated the insecticidal efficacy of monoterpenes against the mosquito Aedes aegypti, the primary dengue vector, via larval bioassay. Employing a low-energy approach, we successfully generated nanoemulsions. The cymene-based nanoemulsion exhibited a hydrodynamic diameter of approximately 98 nm and a zeta potential of -25 mV. The myrcene-based nanoemulsion displayed a hydrodynamic diameter of 118 nm and a zeta potential of -20 mV. Notably, both nanoemulsions demonstrated stability over 60 days, accompanied by controlled release properties and low toxicity towards HaCAT cells and Galleria mellonella larvae. Moreover, the nanoemulsions exhibited significant lethality against third-instar Aedes aegypti larvae at a concentration of 50 mg/L. In conclusion, the utilization of nanoemulsions encapsulating cymene and myrcene presents a promising avenue for overcoming the limitations associated with poor solubility and stability of monoterpenes. This study sheds light on the potential of the nanoemulsions as effective and environmentally friendly insecticides in the ongoing battle against mosquito-borne diseases.

Delivery Strategies of Probiotics from Nano- and Microparticles: Trends in the Treatment of Inflammatory Bowel Disease-An Overview.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, most known as ulcerative colitis (UC) and Crohn's disease (CD), that affects the gastrointestinal tract (GIT), causing considerable symptoms to millions of people around the world. Conventional therapeutic strategies have limitations and side effects, prompting the exploration of innovative approaches. Probiotics, known for their potential to restore gut homeostasis, have emerged as promising candidates for IBD management. Probiotics have been shown to minimize disease symptoms, particularly in patients affected by UC, opening important opportunities to better treat this disease. However, they exhibit limitations in terms of stability and targeted delivery. As several studies demonstrate, the encapsulation of the probiotics, as well as the synthetic drug, into micro- and nanoparticles of organic materials offers great potential to solve this problem. They resist the harsh conditions of the upper GIT portions and, thus, protect the probiotic and drug inside, allowing for the delivery of adequate amounts directly into the colon. An overview of UC and CD, the benefits of the use of probiotics, and the potential of micro- and nanoencapsulation technologies to improve IBD treatment are presented. This review sheds light on the remarkable potential of nano- and microparticles loaded with probiotics as a novel and efficient strategy for managing IBD. Nonetheless, further investigations and clinical trials are warranted to validate their long-term safety and efficacy, paving the way for a new era in IBD therapeutics.

Targeted Polymeric Nanoparticles as a Strategy for the Treatment of Glioblastoma: A Review.

Glioblastoma multiforme is the most common and aggressive malignant tumor that affects the central nervous system, with high mortality and low survival. Glioblastoma multiforme treatment includes resection tumor surgery, followed by radiotherapy and chemotherapy adjuvants. However, the drugs used in chemotherapy present some limitations, such as the difficulty of crossing the bloodbrain barrier and resisting the cellular mechanisms of drug efflux. The use of polymeric nanoparticles has proven to be an effective alternative to circumvent such limitations, as it allows the exploration of a range of polymeric structures that can be modified in order to control the biodistribution and cytotoxic effect of the drug delivery systems. Nanoparticles are nanometric in size and allow the incorporation of targeting ligands on their surface, favoring the transposition of the blood-brain barrier and the delivery of the drug to specific sites, increasing the selectivity and safety of chemotherapy. The present review has described the characteristics of chitosan, poly(vinyl alcohol), poly(lactic-coglycolic acid), poly(ethylene glycol), poly(ß-amino ester), and poly(ε-caprolactone), which are some of the most commonly used polymers in the manufacture of nanoparticles for the treatment of glioblastoma multiforme. In addition, some of the main targeting ligands used in these nanosystems are presented, such as transferrin, chlorotoxin, albumin, epidermal growth factor, and epidermal growth factor receptor blockers, explored for the active targeting of antiglioblastoma agents.

Advances in Diagnostics and Drug Discovery against Resistant and Latent Tuberculosis Infection.

Latent tuberculosis infection (LTBI) represents a subclinical, asymptomatic mycobacterial state affecting approximately 25% of the global population. The substantial prevalence of LTBI, combined with the risk of progressing to active tuberculosis, underscores its central role in the increasing incidence of tuberculosis (TB). Accurate identification and timely treatment are vital to contain and reduce the spread of the disease, forming a critical component of the global strategy known as "End TB." This review aims to examine and highlight the most recent scientific evidence related to new diagnostic approaches and emerging therapeutic treatments for LTBI. While prevalent diagnostic methods include the tuberculin skin test (TST) and interferon gamma release assay (IGRA), WHO's approval of two specific IGRAs for Mycobacterium tuberculosis (MTB) marked a significant advancement. However, the need for a specific test with global application viability has propelled research into diagnostic tests based on molecular diagnostics, pulmonary immunity, epigenetics, metabolomics, and a current focus on next-generation MTB antigen-based skin test (TBST). It is within these emerging methods that the potential for accurate distinction between LTBI and active TB has been demonstrated. Therapeutically, in addition to traditional first-line therapies, anti-LTBI drugs, anti-resistant TB drugs, and innovative candidates in preclinical and clinical stages are being explored. Although the advancements are promising, it is crucial to recognize that further research and clinical evidence are needed to solidify the effectiveness and safety of these new approaches, in addition to ensuring access to new drugs and diagnostic methods across all health centers. The fight against TB is evolving with the development of more precise diagnostic tools that differentiate the various stages of the infection and with more effective and targeted treatments. Once consolidated, current advancements have the potential to transform the prevention and treatment landscape of TB, reinforcing the global mission to eradicate this disease.

A receptor-mediated landscape of druggable and targeted nanomaterials for gliomas.

Gliomas are the most common type of brain cancer, and among them, glioblastoma multiforme (GBM) is the most prevalent (about 60% of cases) and the most aggressive type of primary brain tumor. The treatment of GBM is a major challenge due to the pathophysiological characteristics of the disease, such as the presence of the blood-brain barrier (BBB), which prevents and regulates the passage of substances from the bloodstream to the brain parenchyma, making many of the chemotherapeutics currently available not able to reach the brain in therapeutic concentrations, accumulating in non-target organs, and causing considerable adverse effects for the patient. In this scenario, nanocarriers emerge as tools capable of improving the brain bioavailability of chemotherapeutics, in addition to improving their biodistribution and enhancing their uptake in GBM cells. This is possible due to its nanometric size and surface modification strategies, which can actively target nanocarriers to elements overexpressed by GBM cells (such as transmembrane receptors) related to aggressive development, drug resistance, and poor prognosis. In this review, an overview of the most frequently overexpressed receptors in GBM cells and possible approaches to chemotherapeutic delivery and active targeting using nanocarriers will be presented.

Nanocarrier functionalization strategies for targeted drug delivery in skin cancer therapy: current progress and upcoming challenges.

INTRODUCTION: Skin cancer is the most common form of cancer worldwide, with increasing incidence rates in recent years. Although conventional chemotherapy and radiation therapy have been used for its treatment, these therapies have several limitations such as lack of selectivity and significant side effects. Targeted nanocarriers have emerged as a promising approach for the treatment of skin cancer. AREAS COVERED: This review article provides an overview of targeted nanocarriers for skin cancer treatment. It covers the various types of targeted nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles. EXPERT OPINION: There are still several challenges that need to be addressed before the clinical translation of targeted nanoparticles, such as optimization of their properties, development of reliable and robust characterization methods, and evaluation of their safety and efficacy in clinical trials. Another key aspect for the advancement of these studies is the need to improve regulatory aspects related to the toxicity and regulation of nanomedicines targeting skin cancer. Overall, targeted nanocarriers hold great potential for the development of safe and effective treatments for skin cancer, which can contribute to a better prognosis and overall patients' life quality.

Design of rapamycin and resveratrol coloaded liposomal formulation for breast cancer therapy.

Aims: The development of rapamycin (RAP) and resveratrol (RSV) coloaded liposomes (RAP-RSV-LIP) for breast cancer therapy. Materials & methods: Liposomes were prepared using a high-pressure homogenization technique and evaluated according to their physicochemical characteristics, cellular uptake and cytotoxicity against tumoral and normal cells. Results & conclusion: The RAP-RSV-LIP showed negative surface charge, size around 100 nm, low polydispersity and high encapsulation efficiency for RAP and RSV (58.87 and 63.22%, respectively). RAP-RSV-LIP showed great stability over 60 days and a prolonged drug-release profile. In vitro studies indicated that RAP-RSV-LIP were internalized in an estrogen receptor-positive human breast cancer cell line (MCF-7, 34.2%) and improved cytotoxicity when compared with free drugs. Therefore RAP-RSV-LIP showed great antitumoral potential against breast cancer cells.

Development, characterization and in vitro cytotoxicity of kaempferol-loaded nanostructured lipid carriers in glioblastoma multiforme cells.

Glioblastoma multiforme is the most common and most aggressive human brain cancer. GBM treatment is still a challenge because many drugs are not able to cross the blood-brain barrier, in addition to the increasing resistance to currently available chemotherapy. New therapeutic alternatives are emerging, and, in this context, we highlight kaempferol, a flavonoid with remarkable anti-tumor activity but with limited bioavailability due to its strong lipophilic property. A promising tool to improve the biopharmaceutical properties of molecules such as kaempferol is the use of drug-delivery nanosystems, such as nanostructured lipid carriers (NLC), which can facilitate the dispersion and delivery of highly lipophilic molecules. The present work aimed at the development and characterization of kaempferol-loaded NLC (K-NLC) and the evaluation of its biological properties using in vitro models. The K-NLC showed an average size of 120 nm, zeta potential of - 21 mV, and polydispersity index of 0.099. The K-NLC presented high kaempferol encapsulation efficiency (93%), a drug loading of 3.58%, and a sustained kaempferol release profile for up to 48 h. In addition to presenting a 7-fold increase in kaempferol cytotoxicity, its encapsulation in NLC promoted a cellular uptake of 75%, which corroborates with increased cytotoxicity in U-87MG cells, as observed. Together, these data reinforce the promising antineoplastic properties of kaempferol in addition to the key role of NLC as a platform for the efficient delivery of lipophilic drugs to neoplastic cells, which improved their uptake and therapeutic efficacy in glioblastoma multiforme cells.

New Technological Approaches for Dental Caries Treatment: From Liquid Crystalline Systems to Nanocarriers.

Dental caries is the most common oral disease, with high prevalence rates in adolescents and low-income and lower-middle-income countries. This disease originates from acid production by bacteria, leading to demineralization of the dental enamel and the formation of cavities. The treatment of caries remains a global challenge and the development of effective drug delivery systems is a potential strategy. In this context, different drug delivery systems have been investigated to remove oral biofilms and remineralize dental enamel. For a successful application of these systems, it is necessary that they remain adhered to the surfaces of the teeth to allow enough time for the removal of biofilms and enamel remineralization, thus, the use of mucoadhesive systems is highly encouraged. Among the systems used for this purpose, liquid crystalline systems, polymer-based nanoparticles, lipid-based nanoparticles, and inorganic nanoparticles have demonstrated great potential for preventing and treating dental caries through their own antimicrobial and remineralization properties or through delivering drugs. Therefore, the present review addresses the main drug delivery systems investigated in the treatment and prevention of dental caries.

Polymeric Systems for Colon-specific Mesalazine Delivery in the Intestinal Bowel Diseases Management.

The anti-inflammatory 5-aminosalicylic acid (5-ASA) is the main therapeutic option used to prevent and treat inflammatory bowel diseases. The upper intestinal tract performs rapid and almost complete absorption of this drug when administered orally, making local therapeutic levels of the molecule in the inflamed colonic mucosa difficult to achieve. Micro and nanoparticle systems are promising for 5-ASA incorporation because the reduced dimensions of these structures can improve the drug's pharmacodynamics and contribute to more efficient and localized therapy. Together, the association of these systems with polymers will allow the release of 5-ASA through specific targeting mechanisms to the colon, as demonstrated in the mesalazine modified-release dosage form. This review will summarize and discuss the challenges for the oral administration of 5-ASA and the different colon-specific delivery strategies using polymers.

Epirubicin: Biological Properties, Analytical Methods, and Drug Delivery Nanosystems.

Epirubicin (EPI) is a chemotherapeutic agent belonging to the anthracycline drug class indicated for treating several tumors. It acts by suppressing the DNA and RNA synthesis by intercalating between their base pair. However, several side effects are associated with this therapy, including cardiotoxicity and myelosuppression. Therefore, EPI delivery in nanosystems has been an interesting strategy to overcome these limitations and improve the safety and efficacy of EPI. Thus, analytical methods have been used to understand and characterize these nanosystems, including spectrophotometric, spectrofluorimetric, and chromatography. Spectrophotometric and spectrofluorimetric methods have been used to quantify EPI in less complex matrices due to their efficiency, low cost, and green chemistry character. By contrast, high-performance liquid chromatography is a suitable method for detecting EPI in more complex matrices (e.g., plasm and urine) owing to its high sensitivity. This review summarizes physicochemical and pharmacokinetic properties of EPI, its application in drug delivery nanosystems, and the analytical methods employed in its quantification in different matrices, including blood, plasm, urine, and drug delivery nanosystems.

Pharmaceutical nanotechnology: Antimicrobial peptides as potential new drugs against WHO list of critical, high, and medium priority bacteria.

Nanobiotechnology is a relatively unexplored area that has, nevertheless, shown relevant results in the fight against some diseases. Antimicrobial peptides (AMPs) are biomacromolecules with potential activity against multi/extensively drug-resistant bacteria, with a lower risk of generating bacterial resistance. They can be considered an excellent biotechnological alternative to conventional drugs. However, the application of several AMPs to biological systems is hampered by their poor stability and lifetime, inactivating them completely. Therefore, nanotechnology plays an important role in the development of new AMP-based drugs, protecting and carrying the bioactive to the target. This is the first review article on the different reported nanosystems using AMPs against bacteria listed on the WHO priority list. The current shortage of information implies a nanobiotechnological potential to obtain new drugs or repurpose drugs based on the AMP-drug synergistic effect.

In Vitro Skin Co-Delivery and Antibacterial Properties of Chitosan-Based Microparticles Containing Ascorbic Acid and Nicotinamide.

Vitamins are widely found in nature, for example, in plants and fruits. Ascorbic acid and nicotinamide are examples of these compounds that have potent antioxidant properties, besides stimulating collagen production and depigmenting properties that protect the skin from premature aging. To overcome the skin barrier and reduce the instability of antioxidant compounds, alternative systems have been developed to facilitate the delivery of antioxidants, making them efficiently available to the tissue for an extended time without causing damage or toxicity. The objective of this study was to obtain chitosan biodegradable microparticles containing ascorbic acid and nicotinamide for topical delivery. The microparticles were obtained by spray drying and characterized chemically by means of scanning electron microscopy, infrared spectroscopy, X-ray diffraction, and differential exploratory calorimetry. The drugs were successfully encapsulated and the microparticles showed positive zeta potential. In vitro release assays showed a sustained release profile. The evaluation of ex vivo skin permeation and retention demonstrated low permeation and adequate retention of the compounds in the epidermis/dermis, suggesting the efficient delivery from the obtained microparticles. Antibacterial assays have shown that microparticles can inhibit the growth of microorganisms in a time- and dose-dependent manner, corroborating their use in cosmetic products for application on the skin.

Temozolomide: An Overview of Biological Properties, Drug Delivery Nanosystems, and Analytical Methods.

Temozolomide (TMZ) is an imidazotetrazine prodrug used to treat glioblastoma multiforme. Its physicochemical properties and small size confer the ability to cross the blood-brain barrier. The antitumor activity depends on pH-dependent hydrolysis of the methyldiazonium cation, which is capable of methylating purine bases (O6-guanine; N7-guanine, and N3-adenine) and causing DNA damage and cell death. TMZ is more stable in acidic media (pH ≤ 5.0) than in basic media (pH ≥ 7.0) due to the protonated form that minimizes the catalytic process. Due to this, TMZ has high oral bioavailability, but it has a half-life of 1.8 h and low brain distribution (17.8%), requiring a repeated dosing regimen that limits its efficacy and increases adverse events. Drug delivery Nanosystems (DDNs) improve the physicochemical properties of TMZ and may provide controlled and targeted delivery. Therefore, DDNs can increase the efficacy and safety of TMZ. In this context, to ensure the efficiency of DDNs, analytical methods are used to evaluate TMZ pharmacokinetic parameters, encapsulation efficiency, and the release profile of DDNs. Among the methods, high-performance liquid chromatography is the most used due to its detection sensitivity in complex matrices such as tissues and plasma. Micellar electrokinetic chromatography features fast analysis and no sample pretreatment. Spectrophotometric methods are still used to determine encapsulation efficiency due to their low cost, despite their low sensitivity. This review summarizes the physicochemical and pharmacological properties of free TMZ and TMZ-loaded DDNs. In addition, this review addresses the main analytical methods employed to characterize TMZ in different matrices.

Targeted Liposomes: A Nonviral Gene Delivery System for Cancer Therapy.

Cancer is the second most frequent cause of death worldwide, with 28.4 million new cases expected for 2040. Despite de advances in the treatment, it remains a challenge because of the tumor heterogenicity and the increase in multidrug resistance mechanisms. Thus, gene therapy has been a potential therapeutic approach owing to its ability to introduce, silence, or change the content of the human genetic code for inhibiting tumor progression, angiogenesis, and metastasis. For the proper delivery of genes to tumor cells, it requires the use of gene vectors for protecting the therapeutic gene and transporting it into cells. Among these vectors, liposomes have been the nonviral vector most used because of their low immunogenicity and low toxicity. Furthermore, this nanosystem can have its surface modified with ligands (e.g., antibodies, peptides, aptamers, folic acid, carbohydrates, and others) that can be recognized with high specificity and affinity by receptor overexpressed in tumor cells, increasing the selective delivery of genes to tumors. In this context, the present review address and discuss the main targeting ligands used to functionalize liposomes for improving gene delivery with potential application in cancer treatment.

Glioblastoma multiforme targeted delivery of docetaxel using bevacizumab-modified nanostructured lipid carriers impair in vitro cell growth and in vivo tumor progression.

Glioblastoma multiforme (GBM) is the most common malignant brain cancer, characterized by high invasiveness and poor prognosis. Docetaxel (DTX) is a chemotherapeutic drug with promising anti-tumor properties. However, conventional intravenous formulations exhibit side effects of systemic biodistribution and low brain bioavailability, limiting their clinical use. The current work aimed to evaluate the effect of DTX-loaded nanostructured lipid carriers (NLC) functionalized with bevacizumab (BVZ-NLC-DTX) against GBM using in vitro and in vivo models. The NLC was obtained by the fusion-emulsification method followed by sonication, with narrow size distribution, negative zeta potential, and low polydispersity index. NLC showed DTX entrapment efficiency above 90%. BVZ coupling efficiency was 62% and BVZ integrity after functionalization was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Calorimetry studies confirmed thermal stability and molecular dispersion of DTX in the lipid matrix. NLC showed a sustained DTX release over 84 h. In vitro anti-tumor assays shown that BVZ-NLC-DTX selectively increased the cytotoxic of DTX in cells overexpressing VEGF (U87MG and A172), but not in peripheral blood mononuclear cells (PMBCs), promoting cell death by apoptosis. BVZ functionalization did not impair cellular uptake. An in vivo orthotopic rat model demonstrated that free-DTX was not capable of reducing tumor growth whereas BVZ-NLC-DTX reduced up to 70% tumor volume after 15-days of treatment. Therefore, this study contributes to understanding new nanotechnology-based vehicles capable of reaching the brain more efficiently and repurposing the use of anti-cancer drugs in GBM treatment.