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.

Hybrid Magnetic Lipid-Based Nanoparticles for Cancer Therapy.

Cancer is one of the major public health problems worldwide. Despite the advances in cancer therapy, it remains a challenge due to the low specificity of treatment and the development of multidrug resistance mechanisms. To overcome these drawbacks, several drug delivery nanosystems have been investigated, among them, magnetic nanoparticles (MNP), especially superparamagnetic iron oxide nanoparticles (SPION), which have been applied for treating cancer. MNPs have the ability to be guided to the tumor microenvironment through an external applied magnetic field. Furthermore, in the presence of an alternating magnetic field (AMF) this nanocarrier can transform electromagnetic energy in heat (above 42 °C) through Néel and Brown relaxation, which makes it applicable for hyperthermia treatment. However, the low chemical and physical stability of MNPs makes their coating necessary. Thus, lipid-based nanoparticles, especially liposomes, have been used to encapsulate MNPs to improve their stability and enable their use as a cancer treatment. This review addresses the main features that make MNPs applicable for treating cancer and the most recent research in the nanomedicine field using hybrid magnetic lipid-based nanoparticles for this purpose.

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.

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.

Anti-Candida, docking studies, and in vitro metabolism-mediated cytotoxicity evaluation of Eugenol derivatives.

The high morbidity and mortality rates of Candida infections, especially among immunocompromised patients, are related to the increased resistance rate of these species and the limited therapeutic arsenal. In this context, we evaluated the anti-Candida potential and the cytotoxic profile of eugenol derivatives. Anti-Candida activity was evaluated on C. albicans and C. parapsilosis strains by minimum inhibitory concentration (MIC), scanning electron microscopy (SEM), and molecular docking calculations at the site of the enzyme lanosterol-14-α-demethylase active site, responsible for ergosterol formation. The cytotoxic profile was evaluated in HepG2 cells, in the presence and absence of the metabolizing system (S9 system). The results indicated compounds 1b and 1d as the most active ones. The compounds have anti-Candida activity against both strains with MIC ranging from 50 to 100 µg ml-1 . SEM analyses of 1b and 1d indicated changes in the envelope architecture of both C. albicans and C. parapsilosis like the ones of eugenol and fluconazole, respectively. Docking results of the evaluated compounds indicated a similar binding pattern of fluconazole and posaconazole at the lanosterol-14-α-demethylase binding site. In the presence of the S9 system, compound 1b showed the same cytotoxicity profile as fluconazole (1.08 times) and compound 1d had 1.23 times increase in cytotoxicity. Eugenol and other evaluated compounds showed a significant increase in cytotoxicity. Our results suggest compound 1b as a promising starting point candidate to be used in the design of new anti-Candida agent prototypes.

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.

Highlights in targeted nanoparticles as a delivery strategy for glioma treatment.

Glioma is the most common type of Central Nervous System (CNS) neoplasia and it arises from glial cells. As glial cells are formed by different types of cells, glioma can be classified according to the cells that originate it or the malignancy grade. Glioblastoma multiforme is the most common and aggressive glioma. The high lethality of this tumor is related to the difficulty in performing surgical removal, chemotherapy, and radiotherapy in the CNS. To improve glioma treatment, a wide range of chemotherapeutics have been encapsulated in nanosystems to increase their ability to overcome the blood-brain barrier (BBB) and specifically reach the tumoral cells, reducing side effects and improving drug concentration in the tumor microenvironment. Several studies have investigated nanosystems covered with targeting ligands (e.g., proteins, peptides, aptamers, folate, and glucose) to increase the ability of drugs to cross the BBB and enhance their specificity to glioma through specific recognition by receptors on BBB and glioma cells. This review addresses the main targeting ligands used in nanosystems to overcome the BBB and promote the active targeting of drugs for glioma. Furthermore, the advantages of using these molecules in glioma treatment are discussed.

Electrospun poly(ε-caprolactone) matrices containing silver sulfadiazine complexed with ß-cyclodextrin as a new pharmaceutical dosage form to wound healing: preliminary physicochemical and biological evaluation.

Cooperation between researchers in the areas of medical, pharmaceutical and materials science has facilitated the development of pharmaceutical dosage forms that elicit therapeutic effects and protective action with a single product. In addition to optimizing pharmacologic action, such dosage forms provide greater patient comfort and increase success and treatment compliance. In the present work, we prepared semipermeable bioactive electrospun fibers for use as wound dressings containing silver sulfadiazine complexed with ß-cyclodextrin in a poly(Ɛ-caprolactone) nanofiber matrix aiming to reduce the direct contact between silver and skin and to modulate the drug release. Wound dressings were prepared by electrospinning, and were subjected to ATR-FT-IR and TG/DTG assays to evaluate drug stability. The hydrophilicity of the fibrous nanostructure in water and PBS buffer was studied by goniometry. Electrospun fibers permeability and swelling capacity were assessed, and a dissolution test was performed. In vitro biological tests were realized to investigate the biological compatibility and antimicrobial activity. We obtained flexible matrices that were each approximately 1.0 g in weight. The electrospun fibers were shown to be semipermeable, with water vapor transmission and swelling indexes compatible with the proposed objective. The hydrophilicity was moderate. Matrices containing pure drug modulated drug release adequately during 24 h but presented a high hemolytic index. Complexation promoted a decrease in the hemolytic index and in the drug release but did not negatively impact antimicrobial activity. The drug was released predominantly by diffusion. These results indicate that electrospun PCL matrices containing ß-cyclodextrin/silver sulfadiazine inclusion complexes are a promising pharmaceutical dosage form for wound healing.