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Tatiana Zanela da Silva Marques,1 Ralph Santos-Oliveira,2 Luciana Betzler de Oliveira de Siqueira,1 Verônica da Silva Cardoso,3 Zaida Maria Faria de Freitas,1 Rita de Cássia da Silva Ascenção Barros,1 Ana Lúcia Vazquez Villa,1 Mariana Sato de Souza de Bustamante Monteiro,1 Elisabete Pereira dos Santos,1 Eduardo Ricci-Junior1 1Department of Drugs and Medicines, Faculty of Pharmacy, 2Institute of Nuclear Energy, 3Unit of Biocatalysis, Bioproducts and Bioenergy (Bioinivar), Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil Background: Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo.Methods: The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m.Results: NE1 exhibited droplet size of 26 nm, PDI

Fagner Santos do Carmo,1,2 Eduardo Ricci-Junior,3 Cristal Cerqueira-Coutinho,4 Marta de Souza Albernaz,1,5 Emerson Soares Bernardes,6 Sotiris Missailidis,7 Ralph Santos-Oliveira2 1Rio de Janeiro State University, Biology Institute Roberto Alcantara Gomes, 2Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, 3Federal University of Rio de Janeiro, Faculty of Pharmacy, 4Federal University of Rio de Janeiro, Institute of Macromolecules Eloisa Mano, 5University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, 6Instituto de Pesquisas Energéticas e Nucleares, Centro de Radiofarmácia, São Paulo, 7Institute of Technology in Immunobiologics Bio-Manguinhos, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil Abstract: The early and specific detection of tumors remains a barrier in oncology, especially in cases such as the triple-negative breast cancer (TNBC). To address this gap, aptamers have found an important application in the recognition of tumor biomarkers such as mucin 1 (MUC1). However, there are still some difficulties in the use of aptamer, as their rapid biological clearance makes their use as drugs limited. In this study, the anti-MUC1 aptamer was used as a drug delivery system (DDS) for a radioactive polymeric nanoparticle (NP) in the imaging of TNBCs. Thus, poly(lactic-co-glycolic acid) NPs loaded with the anti-MUC1 aptamer and labeled with technetium-99m were used for a biodistribution study and imaging of TNBC. The results confirmed that the NP was successfully obtained, with a mean size of 262 nm, according to the dynamic light scattering data. The biodistribution assay in induced animal models with TNBC showed that although there was a high capture by intestine (>30%), the DDS developed had a high tumor uptake (5%) and with great in vivo imaging properties, corroborating the possibility of use of this DDS as an imaging drug for TNBC. Keywords: aptamer, cancer control, imaging, nuclear medicine, radiopharmacy

Camila Faria de Amorim Pereira,1,* Michelle Nonato de Oliveira Melo,1,* Vania Emerich Bucco de Campos,2 Ivania Paiva Pereira,1 Adriana Passos Oliveira,1 Mariana Souza Rocha,1 João Vitor da Costa Batista,3,4 Valter Paes de Almeida,5 Irailson Thierry Monchak,5 Eduardo Ricci-Júnior,6 Rafael Garrett,7 Aline Gabrielle Alves Carvalho,7 Jane Manfron,5 Stephan Baumgartner,3,8,9 Carla Holandino1,3 1Multidisciplinary Laboratory of Pharmaceutical Sciences, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2Department of Pharmacy, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil; 3Society for Cancer Research, Hiscia Institute, Arlesheim, Switzerland; 4Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland; 5Postgraduate Program in Pharmaceutical Sciences, Universidade Estadual de Ponta Grossa, Ponta Grossa, Paraná, Brazil; 6Galenic Development Laboratory (LADEG), Department of Drugs and Medicines, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 7Metabolomics Laboratory, Chemistry Institute, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 8Institute of Integrative Medicine, University of Witten/Herdecke, Herdecke, Germany; 9Institute of Complementary and Integrative Medicine, University of Bern, Bern, Switzerland*These authors contributed equally to this workCorrespondence: Carla Holandino, Multidisciplinary Laboratory of Pharmaceutical Sciences, Universidade Federal do Rio de Janeiro, Faculty of Pharmacy, Block B basement, Room 34, 373, Carlos Chagas Filho Avenue, Cidade Universitária, Rio de Janeiro, RJ, 21941-902, Brazil, Email cholandino@gmail.com Stephan Baumgartner, Institute of Complementary and Integrative Medicine, University of Bern, Bern, Switzerland, Email St.Baumgartner@vfk.chBackground and Purpose: Natural products are potential sources of anticancer components. Among various species, the lipophilic extract of the Viscum album subsp. austriacum (Wiesb.) Vollm. (VALE) has shown promising therapeutic potential. The present work aimed to qualify the plant source and characterize the extract’s chemical profile. In addition, a self-nanoemulsifying drug delivery system (SNEDDS) containing VALE (SNEDDS-VALE) was developed.Methods: V. album subsp. austriacum histochemistry was performed, and the chemical profile of VALE was analyzed by GC-MS. After the SNEEDS-VALE development, its morphology was visualized by transmission electron microscopy (TEM), while its stability was evaluated by the average droplet size, polydispersity index (PdI) and pH. Lastly, SNEDDS-VALE chemical stability was evaluated by LC-DAD-MS.Results: The histochemical analysis showed the presence of lipophilic compounds in the leaves and stems. The major compound in the VALE was oleanolic acid, followed by lupeol acetate and ursolic acid. SNEDDS was composed of medium chain triglyceride and Kolliphor® RH 40 (PEG-40 hydrogenated castor oil). A homogeneous, isotropic and stable nanoemulsion was obtained, with an average size of 36.87 ± 1.04 nm and PdI of 0.14 ± 0.02, for 14 weeks.Conclusion: This is the first histochemistry analysis of V. album subsp. austriacum growing on Pinus sylvestris L. which provided detailed information regarding its lipophilic compounds. A homogeneous, isotropic and stable SNEDDS-VALE was obtained to improve the low water solubility of VALE. Further, in vitro and in vivo experiments should be performed, in order to evaluate the antitumoral potential of SNEDDS-VALE. Keywords: Viscum album subsp. austriacum, mistletoe, lipophilic extract, oleanolic acid, SNEDDS

Mariana Sato de Souza de Bustamante Monteiro,1 Rafael Antonio Ozzetti,2 André Luiz Vergnanini,2 Lycia de Brito-Gitirana,3 Nadia Maria Volpato,4 Zaida Maria Faria de Freitas,1 Eduardo Ricci-Júnior,1 Elisabete Pereira dos Santos11Medicines Department, Federal University of Rio de Janeiro, Rio de Janeiro, 2University of Campinas, São Paulo, 3Laboratory of Animal and Comparative Histology, Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, 4Department of Production and Medicine Control, Federal University of Rio Grande do Sul, Rio Grande do Sul, BrazilPurpose: Awareness of the harmful effects of ultraviolet radiation has led to the increasing use of sunscreens, thus, the development of safe and effective antisolar preparations is important. The inclusion of sunscreen molecules in different release systems, like liposomes (lipo) and cyclodextrins (CD) is therefore required.Methods: The in vivo sun protection factor (SPF), water resistance, and in vitro transdermal penetration test of octyl p-methoxycinnamate (OMC) in different dispersions, such as OMC encapsulated in liposomes (lipo/OMC), OMC encapsulated in β-cyclodextrins (β-CD/OMC), OMC encapsulated in both release systems (lipo/OMC and β-CD/OMC), and an OMC-free formulation were determined.Results: Although the formulation containing only the lipo/OMC system revealed high value of in vivo SPF (11.0 ± 1.3) and water resistance (SPF = 10.3 ± 2.2), the formulation containing both release systems (lipo/OMC + β-cyclodextrin/OMC) showed the best result in the in vivo SPF test (11.6 ± 1.6). In the penetration test, the formulation containing the lipo/OMC system had better performance, since a high amount of OMC in the epidermis (18.04 ± 1.17 µg) and a low amount of OMC in the dermis (9.4 ± 2.36 µg) were observed. These results suggest that liposomes interact with the cells of the stratum corneum, promoting retention of OMC in this layer.Conclusion: According to our study, the lipo/OMC system is the most advantageous release system, due to its ability to both increase the amount of OMC in the epidermis and decrease the risk of percutaneous absorption.Keywords: octyl p-methoxycinnamate, sunscreen, liposomes, β-cyclodextrin, penetration

Solid lipid nanoparticles (SLNs) represent promising nanostructures for drug delivery systems. This study successfully synthesized SLNs containing different proportions of babassu oil (BBS) and copaiba oleoresin (COPA) via the emulsification-ultrasonication method. Before SLN synthesis, the identification and quantification of methyl esters, such as lauric acid and β-caryophyllene, were performed via GC-MS analysis. These methyl esters were used as chemical markers and assisted in encapsulation efficiency experiments. A 2 2 factorial design with a center point was employed to assess the impact of stearic acid and Tween 80 on particle hydrodynamic diameter (HD) and polydispersity index (PDI). Additionally, the effects of temperature (8 ± 0.5 °C and 25 ± 1.0 °C) and time (0, 7, 15, 30, 40, and 60 days) on HD and PDI values were investigated. Zeta potential (ZP) measurements were utilized to evaluate nanoparticle stability, while transmission electron microscopy provided insights into the morphology and nanometric dimensions of the SLNs. The in vitro cytotoxic activity of the SLNs (10 µg/mL, 30 µg/mL, 40 µg/mL, and 80 µg/mL) was evaluated using the MTT assay with PC-3 and DU-145 prostate cancer cell lines. Results demonstrated that SLNs containing BBS and COPA in a 1:1 ratio exhibited a promising cytotoxic effect against prostate cancer cells, with a percentage of viable cells of 68.5% for PC-3 at a concentration of 30 µg/mL and 48% for DU-145 at a concentration of 80 µg/mL. These findings underscore the potential therapeutic applications of SLNs loaded with BBS and COPA for prostate cancer treatment.

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([ 223 Ra]RaCl 2 ) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [ 223 Ra]RaCl 2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [ 223 Ra]RaCl 2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [ 223 Ra]RaCl 2 . Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [ 223 Ra]RaCl 2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [ 223 Ra]RaCl 2 . The micellar [ 223 Ra]RaCl 2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [ 223 Ra]RaCl 2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [ 223 Ra]RaCl 2 , in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Nanoceria is a well-known nanomaterial with various properties, including antioxidant, proangiogenic, and therapeutic effects. Despite its potential, there are still aspects that require further exploration, particularly its anti-inflammatory and antimicrobial activities., Method: The global demand for novel anti-inflammatory and antimicrobial drugs underscores the significance of understanding nanoceria in both contexts. In this study, we evaluated the effect of nanoceria on macrophage polarization to better understand its anti-inflammatory effects. Additionally, we investigated the mechanism of action of nanoceria against Cryptococcus neoformans (ATCC 32045), Candida parapsilosis (ATCC 22019), Candida krusei (ATCC 6258), and Candida albicans., Result: The results demonstrated that nanoceria can polarize macrophages toward an anti-inflammatory profile, revealing the cellular mechanisms involved in the anti-inflammatory response. Concerning the antimicrobial effect, it was observed that nanoceria have a more pronounced impact on Candida parapsilosis, leading to the formation of pronounced pores on the surface of this species., Conclusion: Finally, biochemical analysis revealed transitory alterations, mainly in liver enzymes. The data support the use of nanoceria as a potential anti-inflammatory and antimicrobial drug and elucidate some of the mechanisms involved, shedding light on the properties of this nanodrug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nanoparticles has surrounded the population by their use in electronics, medicine and cosmetics. The exposure to nanoparticles coming from different sources is uncountable as the amount of nanoparticles in which a person is exposed daily. In this direction and considering that microcirculation is the main and most affected system by nanoparticles in the first moment, responsible to transport and deal with nanoparticles internally, we evaluated a massive exposure (1 g/Kg) of a well-known nanoparticle (hydroxyapatite) and the impact on the microvessels. The results showed a massive destruction of venules, arterioles, and capillaries when nHAPs were administered topically. However, systemic administration of high doses of nHAP did not affect microcirculation but altered biochemical parameters of blood samples from treated animals. The data demonstrated that even well documented nanoparticles at high doses might affect the whole-body homeostasis. Finally, the results raise the necessity for further investigation of the effect of nanoparticles in microcirculation and the impact in the whole-body homeostasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Radiopharmaceuticals are increasingly playing a leading role in diagnosing, monitoring, and treating disease. In comparison with conventional pharmaceuticals, the development of radiopharmaceuticals does follow the principles of medicinal chemistry in the context of imaging-altered physiological processes. The design of a novel radiopharmaceutical has several steps similar to conventional drug discovery and some particularity. In the present work, we revisited the insights of medicinal chemistry in the current radiopharmaceutical development giving examples in oncology, neurology, and cardiology. In this regard, we overviewed the literature on radiopharmaceutical development to study overexpressed targets such as prostate-specific membrane antigen and fibroblast activation protein in cancer; β-amyloid plaques and tau protein in brain disorders; and angiotensin II type 1 receptor in cardiac disease. The work addresses concepts in the field of radiopharmacy with a special focus on the potential use of radiopharmaceuticals for nuclear imaging and theranostics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Chagas disease, caused by the Trypanosoma cruzi parasitic protozoan, is a neglected tropical disease (NTD) of significant incidence in Latin America. Transmission to humans and other mammals is mainly via the vector insect from the Reduviidae family, popularly known as the kissing bug. There are other transmission means, such as through congenital transmission, blood transfusions, organ transplantations, and the consumption of contaminated food. For more than 50 years, the disease has been treated with benznidazole and nifurtimox, which are only effective during the acute phase of the disease. In addition to their low efficacy in the chronic phase, they cause many adverse effects and are somewhat selective. The use of nanocarriers has received significant attention due to their ability to encapsulate and release therapeutic agents in a controlled manner. Generally, their diameter ranges from 100 to 300 nanometers. The objective of this scoping review was to perform a search of the literature for the use of nanocarriers as an alternative for improving the treatment of Chagas disease and to suggest future research. Bibliographic searches were carried out in the Web of Science and PubMed scientific databases from January 2012 to May 2023, using the "Chagas disease and Trypanosoma cruzi and nanoparticles" keywords, seeking to gather the largest number of articles, which were evaluated using the inclusion and exclusion criteria. After analyzing the papers, the results showed that nanocarriers offer physiological stability and safety for the transport and controlled release of drugs. They can increase solubility and selectivity against the parasite. The in vitro assays showed that the trypanocidal activity of the drug was not impaired after encapsulation. In the in vivo assays, parasitemia reduction and high survival and cure rates in animals were obtained during both phases of the disease using lower doses when compared to the standard treatment. The scoping review showed that nanocarriers are a promising alternative for the treatment of Chagas disease.

Schistosomiasis is a tropical disease transmitted in an aqueous environment by cercariae from the Schistosoma genus. This disease affects 200 million people living in risk areas around the world. The control of schistosomiasis is realized by chemotherapy, wastewater sanitation, health education, and mollusk control using molluscicidal agents. This work evaluates the effects of a nanoemulsion containing essential oil from Myrciaria floribunda leaves as a molluscicidal and cercaricidal agent against Biomphalaria glabrata mollusks and Schistosoma mansoni cercariae. The Myrciaria floribunda essential oil from leaves showed nerolidol, β-selinene, 1,8 cineol, and zonarene as major constituents. The formulation study suggested the F3 formulation as the most promising nanoemulsion with polysorbate 20 and sorbitan monooleate 80 (4:1) with 5% ( w / w ) essential oil as it showed a smaller droplet size of approximately 100 nm with a PDI lower than 0.3 and prominent bluish reflection. Furthermore, this nanoemulsion showed stability after 200 days under refrigeration. The Myrciaria floribunda nanoemulsion showed LC 50 values of 48.11 µg/mL, 29.66 µg/mL, and 47.02 µg/mL in Biomphalaria glabrata embryos, juveniles, and adult mollusks, respectively, after 48 h and 83.88 µg/mL for Schistosoma mansoni cercariae after 2 h. In addition, a survival of 80% was observed in Danio rerio, and the in silico toxicity assay showed lower overall human toxicity potential to the major compounds in the essential oil compared to the reference molluscicide niclosamide. These results suggest that the nanoemulsion of Myrciaria floribunda leaves may be a promising alternative for schistosomiasis control.

Background: Melanoma is a malignant skin cancer type with a high lethality rate due to active metastasis. Among the risk factors for its development is exposure to ultraviolet radiation (UV) and phenotypical characteristics such as clear skin and eyes. Given the difficulties of the conventional therapy, the high cost of the treatment and the low bioavailability of drugs, it is important to develop new therapeutic methods to circumvent this situation. Nanosystems such as micelles, liposomes and nanoparticles present advantages when compared to conventional treatments., Objective: The objective of this paper is to carry out a literature review based on articles that dealt with the use of siRNA-loaded nanosystems for the treatment of melanoma, with trials carried out in vivo to assess tumor size., Methods: The search was conducted in the Web of Science and PubMed databases considering the last 5 years, that is, the period between January 2017 to December 2021. The "SiRNA and Drug Delivery Systems and Melanoma" keywords were used in both databases, and the articles were analyzed using the inclusion and exclusion criteria established for this paper., Results: The results obtained indicated that using siRNA transported via nanosystems was capable of silencing the BRAF tumor genes and of reducing tumor size and weight, not presenting in vitro and/or in vivo toxicity., Conclusion: Such being the case, the development of these systems becomes a non-invasive and promising option for the treatment of melanoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The Aspergillus genus, the etiological agent of aspergillosis, is an important food contaminant and mycotoxin producer. Plant extracts and essential oils are a source of bioactive substances with antimicrobial potential that can be used instead of synthetic food preservatives. Species from the Lauraceae family and the Ocotea genus have been used as traditional medicinal herbs. Their essential oils can be nanoemulsified to enhance their stability and bioavailability and increase their use. Therefore, this study sought to prepare and characterize both nanoemulsion and essential oil from the Ocotea indecora 's leaves, a native and endemic species from the Mata Atlântica forest in Brazil, and evaluate the activity against Aspergillus flavus RC 2054, Aspergillus parasiticus NRRL 2999, and Aspergillus westerdjikiae NRRL 3174. The products were added to Sabouraud Dextrose Agar at concentrations of 256, 512, 1024, 2048, and 4096 µg/mL. The strains were inoculated and incubated for up to 96 h with two daily measurements. The results did not show fungicidal activity under these conditions. A fungistatic effect, however, was observed. The nanoemulsion decreased the fungistatic concentration of the essential oil more than ten times, mainly in A. westerdjikiae . There were no significant changes in aflatoxin production.

The use of targeted alpha therapy (TAT) for bone cancer is increasing each year. Among the alpha radionuclides, radium [ 223 Ra]Ra +2 is the first one approved for bone cancer metastasis therapy. The development of novel radiopharmaceutical based on [ 223 Ra]Ra +2 is essential to continuously increase the arsenal of new TAT drugs. In this study we have developed, characterized, and in vitro evaluated [ 223 Ra] Ra-nano-hydroxyapatite. The results showed that [ 223 Ra] Ra-nano-hydroxyapatite has a dose-response relationship for osteosarcoma cells and a safety profile for human fibroblast cells, corroborating the application as a radiopharmaceutical., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A global need exists for new and more effective contrast agents for computed tomography and traditional X-ray modalities. Among the few options available nowadays, limitations imposed by industrial production, performance, and efficacy restrict the use and reduce the potential of both imaging techniques. The use of nanomaterials as new contrast agents for X-ray and computed tomography is an innovative and viable way to increase the options and enhance performance. In this study, we evaluated eight nanomaterials: hydroxyapatite doped with zinc (Zn-HA 10%); hydroxyapatite doped with strontium (Sr-HA 10%); hydroxyapatite without thermal treatment (HA 282 STT); thermally treated hydroxyapatite (HA 212 500 °C and HA 01.256 CTT 1000 °C); hydroxyapatite microspheres (HA microspheres); gold nanoparticles (AuNP); and graphene oxide doped with copper (Cu-GO). The results showed that for both imaging modalities; HA microspheres were the best option, followed by hydroxyapatite thermally treated at 1000 °C. The nanomaterials with the worst results were hydroxyapatite doped with zinc (Zn-HA 10%), and hydroxyapatite doped with strontium (Sr-HA 10%). Our data demonstrated the potential of using nanomaterials, especially HA microspheres, and hydroxyapatite with thermal treatment (HA 01.256 CTT 1000 °C) as contrast agents for X-ray and computed tomography.

Graphene quantum dots (GQDs), are biocompatible materials, with mechanical strength and stability. Chitosan, has antibacterial and anti-inflammatory properties, and biocompatibility. Wound healing is a challenging process especially in chronic diseases and infection. In this study, films consisting of chitosan and graphene quantum dots were developed for application in infected wounds. The chitosan-graphene films were prepared in the acidic solution followed by slow solvent evaporation and drying. The chitosan-graphene films were characterized by the scanning electron microscopy, x-ray diffraction, atomic force microscopy, Raman spectroscopy and thermogravimetric analysis. The films' was evaluated by the wound healing assays, hemolytic potential, and nitrite production, cytokine production and swelling potential. The obtained films were flexible and well-structured, promoting cell migration, greater antibacterial activity, lower hemolytic activity, and maintaining wound moisture. Our data suggested that the use of graphene quantum dot-containing chitosan films would be an efficient and promising way in combating wounds., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest.

The use of alpha-particle (α-particle) radionuclides, especially [ 223 Ra]RaCl 2 (radium dichloride), for targeted alpha therapy is steadily increasing. Despite the positive clinical outcomes of this therapy, very little data are available about the effect on the ultrastructure of cells. The purpose of this study was to evaluate the nanomechanical and ultrastructure effect of [ 223 Ra] RaCl 2 on cancer cells. To analyze the effect of [ 223 Ra]RaCl 2 on tumor cells, human breast cancer cells (lineage MDA-MB-231) were cultured and treated with the radiopharmaceutical at doses of 2 µCi and 0.9 µCi. The effect was evaluated using atomic force microscopy (AFM) and transmission electron microscopy (TEM) combined with Raman spectroscopy. The results showed massive destruction of the cell membrane but preservation of the nucleus membrane. No evidence of DNA alteration was observed. The data demonstrated the formation of lysosomes and phagosomes. These findings help elucidate the main mechanism involved in cell death during α-particle therapy.

Nanotechnology has changed the world, with a great impact on industry and medicine. In this commentary, we discuss the importance of radiolabeled nanomaterials for the construction of theranostic, imaging and therapeutic agents in order to pave the future of medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The outbreak of coronavirus (COVID-19) has put the world in an unprecedented scenario. To reestablish the world routine as promote the effective treatment of this disease, the world is looking for new (and old) drug that can efficiently kill the virus. In this study, we have developed two nanosystems: polymeric nanoparticles and nanomicelles-based on hydroxychloroquine and azithromycin. The nanosystem was fully characterized by AFM and DLS techniques. Also, the nanosystems were radiolabeled with 99m Tc and pulmonary applied (installation) in vivo to evaluate the biological behavior. The toxicity of both nanosystem were evaluated in primary cells (FGH). Finally, both nanosystems were evaluated in vitro against the SARS-CoV-2. The results demonstrated that the methodology used to produce the nanomicelles and the nanoparticle was efficient, the characterization showed a nanoparticle with a spherical shape and a medium size of 390 nm and a nanomicelle also with a spherical shape and a medium size of 602 nm. The nanomicelles were more efficient (~ 70%) against SARS-CoV-2 than the nanoparticles. The radiolabeling process with 99m Tc was efficient (> 95%) in both nanosystems and the pulmonary application demonstrated to be a viable route for both nanosystems with a local retention time of approximately, 24 h. None of the nanosystems showed cytotoxic effect on FGH cells, even in high doses, corroborating the safety of both nanosystems. Thus, claiming the benefits of the nanotechnology, especially with regard the reduced adverse we believe that the use of nanosystems for COVID-19 treatment can be an optimized choice., Supplementary Information: The online version contains supplementary material available at 10.1007/s40097-022-00476-3., (© The Author(s), under exclusive licence to Islamic Azad University 2022.)

Ionizing radiation has been used for decades and expanded to several applications in multivariate sectors, becoming an important tool to promote controlled chemical reactions in polymeric structures, according to their chemical properties for developing new materials. In addition, the use of radiation can also be applied in order to reduce or eliminate compounds from solutions that may be harmful or of low interest. In this review, we overviewed the chemistry behind material irradiation and the attractive use of ionizing radiation in scientific and industrial development. In this regard, the review was divided into three main sections titled (1) chemical kinetics intermediated by radiation, (2) chemical bonds intermediated by radiation, and (3) radiation chemistry on polymers. We concluded that graft polymerization, crosslinking and chain scission reactions induced by ionizing radiation are very efficient and green strategies for developing new materials with improved properties. Furthermore, water radiolysis plays a key role in the degradation of several contaminants, including pharmaceuticals and microplastics, in aqueous solutions. However, more studies must be conducted to complement the existing theory about the proposed mechanisms responsible for modifying the chemical, mechanical, thermal, optical, and so forth properties of irradiated materials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The use of nanotechnological products is increasing steadily. In this scenario, the application of nanotechnology in food science and as a technological platform is a reality. Among the several applications, the main use of this technology is for the development of foods and nutraceuticals with higher bioavailability, lower toxicity, and better sustainability. In the health field, nano-nutraceuticals are being used as supplementary products to treat an increasing number of diseases. This review summarizes the main concepts and applications of nano-nutraceuticals for health, with special focus on treating cancer and inflammation., Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-022-00338-7., (© The Author(s) under exclusive licence to Sociedade Brasileira de Farmacognosia 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Radiopharmaceuticals are radioactive drugs, with a very short shelf life, in most of the cases. The number of proceedings using radiopharmaceuticals increases each day worldwide and for many countries the price of radiopharmaceuticals can represent a limitation in the offer of this drug for more patients. Nonetheless, the shortage of important radionuclides is a serious issue and may also affect the use and distribution of these drugs for more patients globally, especially in low and middle income countries. In this direction, the need to avoid waste of these drugs is crucial. In this study we have evaluated the stability of two radiopharmaceuticals (MDP and DTPA) under different conditions in order to propose the extension of shelf life. The results showed that is possible to have stable radiopharmaceuticals (both MDP and DTPA) even 24hs post labeling process when storage properly. The data may represent an advance in the field of Radiopharmacy, providing news perspectives for radiopharmaceuticals shelf life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The use of graphene quantum dots as biomedical devices and drug delivery systems has been increasing. The nano-platform of pure carbon has shown unique properties and is approved to be safe for human use. In this study, we successfully produced and characterized folic acid-functionalized graphene quantum dots (GQD-FA) to evaluate their antiviral activity against Zika virus (ZIKV) infection in vitro, and for radiolabeling with the alpha-particle emitting radionuclide radium-223. The in vitro results exhibited the low cytotoxicity of the nanoprobe GQD-FA in Vero E6 cells and the antiviral effect against replication of the ZIKV infection. In addition, our findings demonstrated that functionalization with folic acid doesn't improve the antiviral effect of graphene quantum dots against ZIVK replication in vitro. On the other hand, the radiolabeled nanoprobe 223 Ra@GQD-FA was also produced as confirmed by the Energy Dispersive X-Ray Spectroscopy analysis. 223 Ra@GQD-FA might expand the application of alpha targeted therapy using radium-223 in folate receptor-overexpressing tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The urgency of new contrast agents, especially for X-ray and Computed Tomography (CT) is increasing each day. Although both imaging modalities are the most routinely used imaging techniques, the availability of contrast agent is very limited. In this scenario, the use of graphene quantum dots (GQDs), a member of the graphene family, which has several characteristics, including low toxicity, good biocompatibility and physical-chemical properties, may represent an important application of this material. Thus, using X-ray (conventional) and CT analysis was evaluated the applicability of GQDs as contrast agent for both imaging modalities. The results demonstrated that GQDs are able to attenuate X-ray forming sharp imaging in both modalities. The data broaden the spectrum of GQDs use., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

DEET is considered the gold standard for insect repellent products. However, it behaves as a strong skin permeant. DEET was encapsulated in Solid Lipid Microparticles (SLM) and characterized in terms of morphology, particle size, cytotoxicity and ex vivo permeation. The particles exhibited micrometric size with a spherical shape. In addition, we developed and validated an analytical method for DEET quantification by high performance liquid chromatography (HPLC), which was selective, linear, precise, accurate and robust. The toxicity test in cell culture of keratinocytes, fibroblasts and macrophages showed that the formulation did not present cytotoxicity. The SLM were able to decrease the skin permeation of DEET in relation to the free active in ethanol with gain in the safe. Microparticles were able to increase the skin retention of DEET, which can contribute to extend the time of repellent action. The results showed that Solid Lipid Microparticles are safe and promising topical formulation to insect bite prevention.

Graphene and its derivatives are in the edge of technology with a wide and diverse range of applications. In the last years, especially graphene quantum dots (GQDs) have had their biomedical application expanded in scope, mainly focused on cancer therapy, drug delivery and imaging. Although many studies have evaluated the application of this nanomaterial in biomedical field, only a few studies aimed to understand their biological impact in human health. In this regard, here we evaluated the impact of high doses of GQDs on the microcirculation of a healthy animal model to better assess risks of its use in humans. Our data show that successive applications of GQDs cause irreversible damage to the microcirculation. After seven days, a complete destruction of the microcirculation has been observed. In addition, GQDs showed substantial activity in human erythrocytes. Our findings suggest that risks associated with the use of GQDs, as well as all graphene derivatives, must be better understood, especially concerning biomedical application. A greater understanding of how GQDs impact body circulation, including the context of environmental and engineered nanosystems, is of paramount importance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. Nanomedicine, a term for the application of nanotechnology in medical and health fields, uses nanoparticles for several applications such as imaging, diagnostic, targeted cancer therapy, drug and gene delivery, tissue engineering, and theranostics., Results: Here, we overview the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and radionuclide therapy. Nanostructured radiopharmaceuticals of technetium-99m, copper-64, lutetium-177, and radium-223 are discussed within the scope of this review article., Conclusion: Nanoradiopharmaceuticals may lead to better development of theranostics inspired by ingenious delivery and imaging systems. Cancer nano-theranostics have the potential to lead the way to more specific and individualized cancer treatment., (© 2022. The Author(s).)

Alpha and beta particulate radiation are used for non-treated neoplasia, due to their ability to reach and remain in tumor sites. Radium-223 ( 223 Ra), an alpha emitter, promotes localized cytotoxic effects, while radioactive gold ( 198 Au), beta-type energy, reduces radiation in the surrounding tissues. Nanotechnology, including several radioactive nanoparticles, can be safely and effectively used in cancer treatment. In this context, this study aims to analyze the antitumoral effects of [ 223 Ra]Ra nanomicelles co-loaded with radioactive gold nanoparticles ([ 198 Au]AuNPs). For this, we synthesize and characterize nanomicelles, as well as analyze some parameters, such as particle size, radioactivity emission, dynamic light scattering, and microscopic atomic force. [ 223 Ra]Ra nanomicelles co-loaded with [ 198 Au]AuNPs, with simultaneous alpha and beta emission, showed no instability, a mean particle size of 296 nm, and a PDI of 0.201 (±0.096). Furthermore, nanomicelles were tested in an in vitro cytotoxicity assay. We observed a significant increase in tumor cell death using combined alpha and beta therapy in the same formulation, compared with these components used alone. Together, these results show, for the first time, an efficient association between alpha and beta therapies, which could become a promising tool in the control of tumor progression.

Background: Infectious diseases have the highest mortality rate in the world and these numbers are associated with scarce and/or ineffective diagnosis and bacterial resistance. Currently, with the development of new pharmaceutical formulations, nanotechnology is gaining prominence., Methods: Nanomicelles were produced by ultrasonication. The particle size and shape were evaluated by scanning electron microscopy and confirmed by dynamic light scattering, also thermogravimetric analysis was performed to evaluate the thermal stability. Finally, antibacterial activity has been performed., Results: The results showed that a rod-shaped nanosystem, with 316.1 nm and PDI of 0.243 was formed. The nanosystem was efficient against Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis subsp. spizizenii with MIC inferior to 0.98 and a synergistic effect between silver graphene quantum dots and levofloxacin was observed., Conclusion: The nanosystem produced may rise as a promising agent against the bacterial threat, especially regarding bacterial resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Nanoparticles (NPs) have gained great importance during the last decades for developing new therapeutics with improved outcomes for biomedical applications due to their nanoscale size, surface properties, loading capacity, controlled drug release, and distribution. Among the carbon-based nanomaterials, one of the most biocompatible forms of graphene is graphene quantum dots (GQDs). GQDs are obtained by converting 2D graphene into zero-dimensional graphene nanosheets. Moreover, very few reports in the literature reported the pharmacokinetic studies proving the safety and effectiveness of GQDs for in vivo applications., Objectives: This study evaluated the pharmacokinetics of GQDs radiolabeled with 99m Tc, administered intravenously, in rodents (Wistar rats) in two conditions: short and long periods, to compare and understand the biological behavior., Methods: The graphene quantum dots were produced and characterized by RX diffractometry, Raman spectroscopy, and atomic force microscopy. The pharmacokinetic analysis was performed following the radiopharmacokinetics concepts, using radiolabeled graphene quantum dots with technetium 99 metastable (99mTc). The radiolabeling process of the graphene quantum dots with 99mTc was performed by the direct via., Results: The results indicate that the pharmacokinetic analyses with GQDs over a longer period were more accurate. Following a bicompartmental model, the long-time analysis considers each pharmacokinetic phase of drugs into the body. Furthermore, the data demonstrated that short-time analysis could lead to distortions in pharmacokinetic parameters, leading to misinterpretations., Conclusion: The evaluation of the pharmacokinetics of GQDs over long periods is more meaningful than the evaluation over short periods., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. It is a long-lasting autoimmune disease, which mainly affects the joints causing inflammation and swelling of the synovial joint. RA has a significant impact on the ability to perform daily activities including simple work and household chores. Nonetheless, due to the long periods of pain and the continuous use of anti-inflammatory drugs, RA can debilitate the quality of life and increases mortality. Current therapeutic approaches to treat RA aim to achieve prolonged activity and early and persistent remission of the disease, with the gradual adoption of different drugs available. In this study, we developed a novel hydroxychloroquine and methotrexate co-loaded Pluronic® F-127 nanomicelle and evaluated its therapeutic effects against RA. Our results showed that drug-loaded nanomicelles were capable of modulating the inflammatory process of RA and reducing osteoclastogenesis, edema, and cell migration to the joint. Overall, compared to the free drugs, the drug-loaded nanomicelles showed a 2-fold higher therapeutic effect., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Malaria is the most common parasitic disease around the world, especially in tropical and sub-tropical regions. This parasitic disease can have a rapid and severe evolution. It is transmitted by female anopheline mosquitoes. There is no reliable vaccine or diagnostic test against malaria; instead, Artesunate is used for the treatment of severe malaria and Artemisinin is used for uncomplicated falciparum malaria. However, these treatments are not efficient against severe malaria and improvements are needed. Primaquine (PQ) is one of the most widely used antimalarial drugs. It is the only available drug to date for combating the relapsing form of malaria. Nevertheless, it has severe side effects. Particle drug-delivery systems present the ability to enhance the therapeutic properties of drugs and decrease their side effects. Here, we report the development of Polymeric Primaquine Microparticles (PPM) labeled with 99mTc for therapeutic strategy against malaria infection. The amount of primaquine encapsulated into the PPM was 79.54%. PPM presented a mean size of 929.47 ± 37.72 nm, with a PDI of 0.228 ± 0.05 showing a homogeneous size for the microparticles and a monodispersive behavior. Furthermore, the biodistribution test showed that primaquine microparticles have a high liver accumulation. In vivo experiments using mice show that the PPM treatments resulted in partial efficacy and protection against the development of the parasite compared to free Primaquine. These results suggest that microparticles drug delivery systems of primaquine could be a possible approach for malaria prevention and treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nanotechnology has gained significant importance in different fields of medical, electronic, and environmental science. This technology is founded on the use of materials at the nanoscale scale (1-100 nanometers) for various purposes, particularly in the biomedical area, where its application is growing daily due to the need of materials with advanced properties. Over the past few years, there has been a growing use for graphene and its derivative composite materials. However, different physico-chemical properties influence its biological response; therefore, further studies to explain the interactions of these nanomaterials with biological systems are critical. This review presents the current advances in the applications of graphene in biomedicine with a focus on the physico-chemical characteristics of the graphene family and their influences on biological interactions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Melanoma is an invasive and very aggressive skin cancer due to its multi-drug resistance that results in poor patient survival. There is a need to test new treatment approaches to improve therapeutic efficacy and reduce side effects of conventional treatments., Methods: PLA/PVA nanoparticles carrying both Dacarbazine and zinc phthalocyanine was produced by double emulsion technique. The characterization was performed by dynamic light scattering and atomic force microscopy. In vitro photodynamic therapy test assay using MV3 melanoma cells as a model has been performed. In vitro cell viability (MTT) was performed to measure cell toxicity of of nanoparticles with and without drugs using human endothelial cells as a model. The in vivo assay (biodistribution/tissue deposition) has been performed using radiolabeled PLA/PVA NPs., Results: The nanoparticles produced showed a mean diameter of about 259 nm with a spherical shape. The in-vitro photodynamic therapy tests demonstrated that the combination is critical to enhance the therapeutic efficacy and it is dose dependent. The in vitro cell toxicity assay using endothelial cells demonstrated that the drug encapsulated into nanoparticles had no significant toxicity compared to control samples. In-vivo results demonstrated that the drug loading affects the biodistribution of the nanoparticle formulations (NPs). Low accumulation of the NPs into the stomach, heart, brain, and kidneys suggested that common side effects of Dacarbazine could be reduced., Conclusion: This work reports a robust nanoparticle formulation with the objective to leveraging the synergistic effects of chemo and photodynamic therapies to potentially suppressing the drug resistance and reducing side effects associated with Dacarbazine. The data corroborates that the dual encapsulated NPs showed better in-vitro efficacy when compared with the both compounds alone. The results support the need to have a dual modality NP formulation for melanoma therapy by combining chemotherapy and photodynamic therapy.

The use of graphene quantum dots as biomedical device and drug delivery system has been increasing. This nanoplatform of pure carbon has showed unique properties and showed to be safe for human use. The imatinib is a molecule designed to specifically inhibit the tyrosine kinase, used for leukemia treatment. In this study, we successfully decorated the graphene quantum dots (GQDs@imatinb) by a carbodiimide crosslinking reaction. The GQDs@imatinb were characterized by FTIR and AFM. The nanoparticles' in vitro behaviors were evaluated by cellular trafficking (internalization) assay and cell viability and apoptosis assays in various cancer cell lines, including suspension (leukemia) cells and adherent cancer cells. The results showed that the incorporation of the imatinib on the surface of the graphene quantum dots did not change the nanoparticles' morphology and properties. The GQDs@imatinb could be efficiently internalized and kill cancer cells via the induction of apoptosis. The data indicated that the prepared GQDs@imatinb might be a great drug nano-platform for cancer, particularly leukemia treatments., Competing Interests: Declaration of competing interest The authors state that do not have any conflicts of interest.

Graphene, including graphene quantum dots, its oxide and unoxidized forms (pure graphene) have several properties, like fluorescence, electrical conductivity, theoretical surface area, low toxicity, and high biocompatibility. In this study, we evaluated genotoxicity ( in silico analysis using the functional density theory-FDT), cytotoxicity (human glioblastoma cell line), in vivo pharmacokinetics, in vivo impact on microcirculation and cell internalization assay. It was also radiolabeled with lutetium 177 (177Lu), a beta emitter radioisotope to explore its therapeutic use as nanodrug. Finally, the impact of its disposal in the environment was analyzed using ecotoxicological evaluation. FDT analysis demonstrated that graphene can construct covalent and non-covalent bonds with different nucleobases, and graphene oxide is responsible for generation of reactive oxygen species (ROS), corroborating its genotoxicity. On the other hand, non-cytotoxic effect on glioblastoma cells could be demonstrated. The pharmacokinetics analysis showed high plasmatic concentration and clearance. Topical application of 0.1 and 1 mg/kg of graphene nanoparticles on the hamster skinfold preparation did not show inflammatory effect. The cell internalization assay showed that 1-hour post contact with cells, graphene can cross the plasmatic membrane and accumulate in the cytoplasm. Radio labeling with 177Lu is possible and its use as therapeutic nanosystem is viable. Finally, the ecotoxicity analysis showed that A. silina exposed to graphene showed pronounced uptake and absorption in the nauplii gut and formation of ROS. The data obtained showed that although being formed exclusively of carbon and carbon-oxygen, graphene and graphene oxide respectively generate somewhat contradictory results and more studies should be performed to certify the safety use of this nanoplatform.

Nowadays, emerging radiolabeled nanosystems are revolutionizing medicine in terms of diagnostics, treatment, and theranostics. These radionuclides include polymeric nanoparticles (NPs), liposomal carriers, dendrimers, magnetic iron oxide NPs, silica NPs, carbon nanotubes, and inorganic metal-based nanoformulations. Between these nano-platforms, polymeric NPs have gained attention in the biomedical field due to their excellent properties, such as their surface to mass ratio, quantum properties, biodegradability, low toxicity, and ability to absorb and carry other molecules. In addition, NPs are capable of carrying high payloads of radionuclides which can be used for diagnostic, treatment, and theranostics depending on the radioactive material linked. The radiolabeling process of nanoparticles can be performed by direct or indirect labeling process. In both cases, the most appropriate must be selected in order to keep the targeting properties as preserved as possible. In addition, radionuclide therapy has the advantage of delivering a highly concentrated absorbed dose to the targeted tissue while sparing the surrounding healthy tissues. Said another way, radioactive polymeric NPs represent a promising prospect in the treatment and diagnostics of cardiovascular diseases such as cardiac ischemia, infectious diseases such as tuberculosis, and other type of cancer cells or tumors.

Cancer is a global epidemic disease responsible for over ten millions death worldwide. The early diagnosis and the precise treatment with reduced adverse reactions are the main goal worldwide. In this study, we produced, characterized and evaluated ( in vitro) in three different cancer cell lines (protaste, breast and melanoma) a radioactive gold nanocluster (R-AuNC) ( 198 Au25(Capt)18). The pharmacokinetics as the influence in the ABC transporter (MRP1 Efflux Transporter Protein) was also evaluated. The results showed that R-AuNC ( 198 Au25(Capt)18) are capable to kill the cancer cells lines of protaste, breast and melanoma. The pharmacokinetics showed a fast clearance and great volume of distribution, confirming the use of R-AuNC as nanomedicine for cancer treatment. Finally, the ABC transporter assay corroborated that the R-AuNC ( 198 Au25(Capt)18) has no risk of being pumped out of cells by this efflux transporter. The results validate the use of gold nanoparticles as therapeutic nanomedicine for cancer treatment.

Lycopene is a carotenoid drug that has demonstrated several properties, including antioxidant and anti-inflammatory activity. The absorption in human body is very low (10-30 % only). In order to increase the bioavailability, lycopene nanoemulsion was formulated and characterized (atomic force microscopy, thermogravimetric analysis dynamic light scattering and differential scanning calorimetry). Also in vitro assay to evaluate the at-binding with MPR1 was performed. Finally, in vivo assay in animals inducted with rheumathoid arthritis were performed. The results showed that the formulated nanolycopene had superior efficacy when compared with the conventional lycopene (not nano-formulated) in inducted animals (rheumatoid arthritis). The results support the use of nanolycopene as an anti-inflammatory agent for rheumatoid arthritis therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purposes: Senescence is an inevitable and irreversible process, which may lead to loss in muscle and bone density, decline in brain volume and loss in renal clearance. Although aging is a well-known process, few studies on the consumption of nanodrugs by elderly people were performed., Methods: We evaluated three different nanosystems: i) carbon based nanosystem (Graphene Quantum Dots, GQD), ii) polymeric nanoparticles and mesoporous silica (magnetic core mesoporous silica, MMSN). In previous studies, our group has already characterized GQD and MMSN nanoparticles by dynamic light scattering analysis, atomic force microscopy, transmission electron microscopy, X-ray diffraction, Raman analysis, fluorescence and absorbance. The polymeric nanoparticle has been characterized by AFM and DLS. All the nanosystems were radiolabeled with 99 m-Tc by. The in vivo biodistribution/tissue deposition analysis evaluation was done using elder (PN270) and young (PN90) mice injected with radioactive nanosystems., Results: The nanosystems used in this study were well-formed as the radiolabeling processes were stable. Biodistribution analysis showed that there is a decrease in the uptake of the nanoparticles in elder mice when compared to young mice, showing that is necessary to increase the initial dose in elder people to achieve the same concentration when compared to young animals., Conclusion: The discrepancy on tissue distribution of nanosystems between young and elder individuals must be monitored, as the therapeutic effect will be different in the groups. Noteworthy, this data is an alarm that some specific conditions must be evaluated before commercialization of nano-drugs. Graphical Abstract Changes between younger and elderly individuals are undoubtedly, especially in drug tissue deposition, biodistribution and pharmacokinetics. The same thought should be applied to nanoparticles. A comprehensive analysis on how age discrepancy change the biological behavior of nanoparticles has been performed.

: Nanodrugs have in recent years been a subject of great debate. In 2017 alone, almost 50 nanodrugs were approved for clinical use worldwide. Despite the advantages related to nanodrugs/nanomedicine, there is still a lack of information regarding the biological safety, as the real behavior of these nanodrugs in the body. In order to better understand these aspects, in this study, we evaluated the effect of polylactic acid (PLA) nanoparticles (NPs) and magnetic core mesoporous silica nanoparticles (MMSN ) , of 1000 nm and 50 nm, respectively, on human cells. In this direction we evaluated the cell cycle, cytochemistry, proliferation and tubulogenesis on tumor cells lines: from melanoma (MV3), breast cancer (MCF-7, MDA-MB-213), glioma (U373MG), prostate (PC3), gastric (AGS) and colon adenocarcinoma (HT-29) and non-tumor cell lines: from human melanocyte (NGM), fibroblast (FGH) and endothelial (HUVEC), respectively. The data showed that an acute exposure to both, polymeric nanoparticles or MMSN, did not show any relevant toxic effects on neither tumor cells nor non-tumor cells, suggesting that although nanodrugs may present unrevealed aspects, under acute exposition to human cells they are harmless.

Increasing resistance to current fungicides is a clinical problem that leads to the need for new treatment strategies. Clove oil (CO) has already been described as having antifungal action. However, it should not be applied directly to the skin as it may be irritating. One option for CO delivery and suitable topical application would be nanoemulsions (NEs). NEs have advantages such as decreased irritant effects and lower dose use. The purpose of this work was the development of NEs containing CO and in vitro evaluation against Candida albicans and Candida glabrata. The NEs were produced by an ultrasonic processor with different proportions of CO and Pluronic ® F-127. In order to determine the best composition and ultrasound amplitude, an experimental design was performed. For the evaluation, droplet size and polydispersity index (PdI) were used. After the stability study, in vitro activity against C. albicans and C. glabrata was evaluated. NEs selected for the stability study, with diameter <40 nm and PdI <0.2, remained stable for 420 d. Activity against Candida spp. was improved when the CO was nanoemulsified, for it possibly leads to a better interaction between the active and the microorganisms, mainly in C. albicans.