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Targeting drugs to the central nervous system (CNS) is challenging due to the presence of the blood-brain barrier (BBB). The cutting edge in nanotechnology generates optimism to overcome the growing challenges in biomedical sciences through the effective engineering of nanogels. The primary objective of the present report was to develop and characterize a biocompatible natural chitosan (CS)-based NG that can be tracked thanks to the tricarbocyanine (CNN) fluorescent probe addition on the biopolymer backbone. FTIR shed light on the chemical groups involved in the CS and CNN interactions and between CNN-CS and tripolyphosphate, the cross-linking agent. Both in vitro and in vivo experiments were carried out to determine if CS-NGs can be utilized as therapeutic delivery vehicles directed towards the brain. An ionic gelation method was chosen to generate cationic CNN-CS-NG. DLS and TEM confirmed that these entities' sizes fell into the nanoscale. CNN-CS-NG was found to be non-cytotoxic, as determined in the SH-SY5Y neuroblastoma cell line through biocompatibility assays. After cellular internalization, the occurrence of an endo-lysosomal escape (a crucial event for an efficient drug delivery) of CNN-CS-NG was detected. Furthermore, CNN-CS-NG administered intraperitoneally to female CF-1 mice were detected in different brain regions after 2 h of administration, using fluorescence microscopy. To conclude, the obtained findings in the present report can be useful in the field of neuro-nanomedicine when designing drug vehicles with the purpose of delivering drugs to the CNS.

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ABSTRACT Objective: To map the nanocomposites used in the treatment of skin lesions. Method: A scoping review, according to the Joanna Briggs Institute methodology, carried out on eight databases, a list of references and Google Scholar to answer the question: "Which nanocomposites are used as a cover for the treatment of skin lesions?". Two independent reviewers selected the final sample using inclusion/exclusion criteria using the EndNote® and Rayyan programs. Data was extracted using an adapted form and reported using the PRISMA checklist extension, and the protocol was registered in the Open Science Framework (OSF). Results: 21 articles were selected, with nanofibers, nanogels and nanomembranes as the nanocomposites described in wound healing, alone or in association with other therapies: negative pressure and elastic. Silver nanomaterials stand out in accelerating healing due to their antimicrobial and anti-inflammatory action, but caution should be exercised due to the risk of cytotoxicity and microbial resistance. Conclusion: Nanocomposites used in wound treatment are effective in accelerating healing and reducing costs, and the addition of bioactives to nanomaterials has added extra properties that contribute to healing.

RESUMEN Objetivo: Mapear los nanocompuestos utilizados en el tratamiento de lesiones cutáneas. Método: Revisión de alcance, según la metodología del Instituto Joanna Briggs, realizada sobre ocho bases de datos, una lista de referencias y Google Scholar para responder a la pregunta: "¿Qué nanocompuestos se utilizan como cobertura para el tratamiento de lesiones cutáneas?". Dos revisores independientes seleccionaron la muestra final mediante criterios de inclusión/exclusión utilizando los programas EndNote® y Rayyan. Los datos se extrajeron mediante un formulario adaptado y se notificaron utilizando la extensión de la lista de comprobación PRISMA, y el protocolo se registró en el Open Science Framework (OSF). Resultados: Se seleccionaron 21 artículos, con nanofibras, nanogeles y nanomembranas como los nanocompuestos descritos en la cicatrización de heridas, solos o en asociación con otras terapias: presión negativa y elástica. Los nanomateriales con plata destacan en la aceleración de la cicatrización por su acción antimicrobiana y antiinflamatoria, pero se recomienda precaución en su uso por el riesgo de citotoxicidad y resistencia microbiana. Conclusión: Los nanocompuestos utilizados en el tratamiento de heridas son eficaces para acelerar la cicatrización y reducir costes, y la adición de bioactivos a los nanomateriales ha añadido propiedades adicionales que contribuyen a la cicatrización.

RESUMO Objetivo: Mapear os nanocompostos utilizados no tratamento de lesões cutâneas. Método: Revisão de escopo, conforme metodologia Joanna Briggs Institute, realizada em oito bases de dados, lista de referências e Google Scholar para responder à pergunta: "Quais os nanocompostos utilizados como cobertura para o tratamento de lesões cutâneas?". Dois revisores independentes, selecionaram a amostra final mediante critérios de inclusão/exclusão usando os programas EndNote® e Rayyan. Os dados foram extraídos com formulário adaptado e reportados pela extensão do checklist PRISMA, o protocolo foi registrado na Open Science Framework (OSF). Resultados: 21 artigos selecionados, trouxeram nanofibras, nanogéis e nanomembranas como os nanocompostos descritos na cicatrização de feridas, isolados ou em associação a outras terapias: pressão negativa e elástica. Os nanomateriais com prata destacam-se em acelerar a cicatrização pela ação antimicrobiana e anti-inflamatória, recomenda-se cautela no uso pelo risco de citotoxicidade e resistência microbiana. Conclusão: Os nanocompostos utilizados no tratamento de feridas são eficientes em acelerar a cicatrização e reduzir custos, a adição de bioativos aos nanomateriais agregaram propriedades extras que contribuem com a cicatrização.

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"Smart" nanogels are an attractive tool for the development of new strategies of immunization in veterinary medicine. Here, we reported the synthesis and physicochemical characterization of thermoresponsive nanogels based on poly(N-isopropylacrylamide) (pNIPAM) and theirin vitro, ex vivoand in vivo (mice model) performance. Smart nanogels of ca. 250 nm, with a transition temperature of 32 °C were obtained by precipitation polymerization. Assays to evaluatepNIPAM nanogels cytotoxicity were performed in different cell lines showing high biocompatibility (>70 %). The efficient internalization of the system was studied by confocal microscopy as well as flow cytometry. The ability to protect and deliver antigens was analyzed using the outer membrane lipoprotein A (OmlA), an important virulence factor ofActinobacillus pleuropneumoniae(App)cause of porcine pleuropneumonia. This lipoprotein was synthesized by recombinant technology and its technique was also described. The biodistribution ofpNIPAM nanogels administered intranasally was performedinvivo and ex vivo through Pearl Imaging System, which showed that nanogels were kept mostly in the lungs during the evaluated time. Besides, the efficacy of the proposal nanogel-based vaccine was studiedin vivoby measuring the antibody titers of BALB/c mice inoculated with OmlA encapsulated intopNIPAM nanogels compared to OmlA plus aluminum hydroxide adjuvant. The results proved the ability of nanogels to stimulate a humoral immune response. Therefore, we have demonstrated thatpNIPAM nanogels can be used as an efficient platform for vaccine nanocarriers.

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Polymeric-inorganic hybrid nanomaterials have emerged as novel multifunctional platforms because they combine the intrinsic characteristics of both materials with unexpected properties that arise from synergistic effects. In this work, hybrid nanogels based on mesoporous silica nanoparticles, oligo (ethylene glycol) methacrylates, and acidic moieties were developed employing ultrasound-assisted free radical precipitation/dispersion polymerization. Chemical structure was characterized by infrared spectroscopy and nuclear magnetic resonance. Hydrodynamic diameters at different temperatures were determined by dynamic light scattering, and cloud point temperatures were determined by turbidimetry. Cell viability in fibroblast (NIH 3T3) and human prostate cancer (LNCaP) cell lines were studied by a standard colorimetric assay. The synthetic approach allows covalent bonding between the organic and inorganic components. The composition of the polymeric structure of hybrid nanogels was optimized to incorporate high percentages of acidic co-monomer, maintaining homogeneous nanosized distribution, achieving appropriate volume phase transition temperature values for biomedical applications, and remarkable pH response. The cytotoxicity assays show that cell viability was above 80% even at the highest nanogel concentration. Finally, we demonstrated the successful cell inhibition when they were treated with camptothecin-loaded hybrid nanogels.

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Preparations for topical application are highly important for therapeutic and cosmetic use since the skin has an extensive and accessible application area. Among the many advantages, this route avoids the systemic effects of the substances and, therefore, fewer adverse reactions are observed. However, the skin is an organ with a remarkable barrier effect, which can compromise the administration of pharmacologically / cosmetologically active molecules. Thus, the skin permeability of substances is a challenge that is only achieved through the preparation of formulations capable of overcoming that same barrier. Nanotechnology was introduced in the pharmaceutical and cosmetic areas to enable the development of systems for the delivery of substances and the optimization of already existing formulations. Among the several benefits and advantages of nanotechnology for topical application is the increased penetration of the drug in the skin, the improvement of the stability of the active, decrease in the active substances (reducing the possible toxic effects and allergic reactions caused by the high concentration of these compounds), and even the intensification of the drug action. This manuscript reviews the topical delivery technologies based on polymeric nanocarriers (PNC) as nanoparticles (NP) and nanogels (NG) and their benefits for better efficacy in most common cutaneous disorders. It starts with skin properties, the aspects for the penetration of active ingredients in the skin and cutaneous penetration challenges, followed by a summary of strategies for skin penetration/permeation of drugs. Then, the focus of the current research was to review NPs and NGs explored for skin disorders management published during the last years.

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Transcutaneous immunization (TCI) provides a valuable alternative approach to conventional vaccination because of the high accessibility and the exceptional immunological characteristics of the skin, but its application is limited by the low permeability of the stratum corneum. Although nanogels (NGs) have proven to enhance skin penetration of macromolecules with minimum damage, their use in TCI remains almost unexplored. In this context, this article evaluates the performance of novel film-forming NGs (FF-NGs) as TCI. This TCI platform consists of NGs with multilobular morphology that positively combines the properties of cross-linked poly(N-vinylcaprolactam), like thermoresponsiveness and the ability to load and release a cargo, with the film-forming capacity of low Tg lobes. FF-NGs and formed films are characterized at different levels. Formed films show to be able to uniformly load an antigenic protein and release it with a profile depending on the temperature and on their FF-NGs content. In vivo studies have demonstrated that FF-NGs promote the penetration of not only an antigenic protein, but also an adjuvant until the immunocompetent area of skin, generating an adjuvant-dependent specific immune response. Finally, this study provides a successful proof of concept that FF-NGs can be a powerful tool for the transcutaneous release of complex formulations.

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Dual-function nanogels (particle size from 98 to 224 nm) synthesized via surfactant-free emulsion polymerization (SFEP) were tested as smart carriers toward synergistic chemo- and photothermal therapy. Cisplatin (CDDP) or doxorubicin (DOX) and gold nanorods (GNRDs) were loaded into galacto-functionalized PNVCL-based nanogels, where the encapsulation efficiency for CDDP and DOX was around 64 and 52%, respectively. PNVCL-based nanogels were proven to be an efficient delivery vehicle under conditions that mimic the tumor site in vitro. The release of CDDP or DOX was slower at pH 7.4 and 37 °C than at tumor conditions of pH 6 and 40 °C. On the other hand, in the systems with GNRDs at pH 7.4 and 37 °C, the sample was irradiated with a 785 nm laser for 10 min every hour, obtaining that the release profiles were even higher than in the conditions that simulated a cancer tissue (without irradiation). Thus, the present study demonstrates the synergistic effect of chemo- and photothermal therapy as a promising dual function in the potential future use of PNVCL nanogels loaded with GNRDs and CDDP/DOX to achieve an enhanced chemo/phototherapy in vivo.

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Field experiments were carried out in the reclaimed land east of Cairo-Alexandria Desert Road, Village of Wardan, Giza Governorate, Egypt, to evaluate the impact of using nano-gels pheromone for the first time on the attraction of the RPW adults by pheromone traps compared to the control which is normal pheromone during two successive seasons in 2018 and 2019. Also, this study aimed to compare the efficacy of two types of trap, traditional trap (type 1) and dry funnel trap (type 2) in capturing of RPW adults. Results revealed that the nano gel pheromone traps attracted significantly more adults with an average of (4.26 and 3.56) adults/trap and total of (55.33 and 46.33) adults/trap compared to control with an average (2.69 and 2.46) and total of (35.00 and 32.00) adults/trap for the two seasons 2018 and 2019 respectively. Results indicated that the use of nano gel pheromone for the first time in field improved the trap catchability to RPW adults by 22.51 and 18.30% of total number of RPW adults captured throw out the two successive seasons respectively. In addition, there was no significant difference between the total numbers of RPW adults collected by the two tested type of traps over the two successive seasons. Furthermore, the sex ratio between males and females of total collected RPW adults found to be1: 1.43 and 1: 1.94 at 2018 and 2019 respectively.(AU)

Experimentos de campo foram realizados na terra recuperada a leste da estrada do deserto de Cairo-Alexandria, vila de Wardan, província de Giza, Egito, para avaliar o impacto do uso de feromônio de nano géis pela primeira vez na atração de adultos RPW por armadilhas de feromônio comparado ao controle que é o feromônio normal durante duas temporadas sucessivas em 2018 e 2019. Além disso, este estudo teve como objetivo comparar a eficácia de dois tipos de armadilha, armadilha tradicional (tipo 1) e armadilha de funil seco (tipo 2) na captura de RPW adultos. Os resultados revelaram que as armadilhas de nano gel de feromônio atraíram significativamente mais adultos, com uma média de (4,26 e 3,56) adultos/armadilha e total de (55,33 e 46,33) adultos/armadilha em comparação ao controle com uma média (2,69 e 2,46) e total de (35.00 e 32.00) adultos/armadilha para as duas temporadas 2018 e 2019, respectivamente. Os resultados indicaram que o uso de feromônio nano gel pela primeira vez em campo melhorou a capturabilidade de armadilhas para adultos com RPW em 22,51 e 18,30% do número total de adultos com RPW capturados durante as duas estações sucessivas, respectivamente. Além disso, não houve diferença significativa entre o número total de adultos RPW coletados pelos dois tipos de armadilhas testados ao longo das duas estações sucessivas. Além disso, a proporção sexual entre homens e mulheres do total de adultos coletados de RPW foi de 1: 1,43 e 1: 1,94 em 2018 e 2019, respectivamente.(AU)

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Although this is an era of pandemics and many devastating diseases, this is also a time when bionanotechnology flourishes, illuminating a multidisciplinary field where vaccines are quickly becoming a balsam and a prevention against insidious plagues. In this work, we tried to gain and also give a deeper understanding on nanovaccines and their way of acting to prevent or cure cancer, infectious diseases, and diseases caused by parasites. Major nanoadjuvants and nanovaccines are temptatively exemplified trying to contextualize our own work and its relative importance to the field. The main properties for novel adjuvants seem to be the nanosize, the cationic character, and the biocompatibility, even if it is achieved in a low dose-dependent manner.

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Topical administration to the eye for the treatment of glaucoma is a convenient route because it increases the patient comfort. Timolol can efficiently diminish the intraocular pressure (IOP) of the eye; however the topical application as a solution of timolol maleate (TM) has poor therapeutic index and presents severe side effects. The encapsulation of timolol in nanomaterials has appeared as a technology to increase its residence time in the eye thus achieving a sustained release and consequently diminishing the doses of this drug and their number. The preparation of nanogels (NGs) based on N-isopropylacrylamide (NIPA) and acrylic acid (AAc), easily synthesized by precipitation/dispersion free radical polymerization, is reported in this paper. Such NGs presented excellent dispersability in eye simulated fluid and ideal size for topical application. NGs can load efficiently timolol through ionic interaction, and the in vitro release showed that NGs deliver timolol in a sustained manner. In vivo sustained efficacy of the NGs-timolol nanoformulations was demonstrated in rabbit's glaucoma model, in which the IOP could be diminished and maintained constant for 48 h with only one application. Overall, the synthesized NGs in combination with timolol have potential as drug delivery system for glaucoma therapy.

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Field experiments were carried out in the reclaimed land east of Cairo-Alexandria Desert Road, Village of Wardan, Giza Governorate, Egypt, to evaluate the impact of using nano-gels pheromone for the first time on the attraction of the RPW adults by pheromone traps compared to the control which is normal pheromone during two successive seasons in 2018 and 2019. Also, this study aimed to compare the efficacy of two types of trap, traditional trap (type 1) and dry funnel trap (type 2) in capturing of RPW adults. Results revealed that the nano gel pheromone traps attracted significantly more adults with an average of (4.26 and 3.56) adults/trap and total of (55.33 and 46.33) adults/trap compared to control with an average (2.69 and 2.46) and total of (35.00 and 32.00) adults/trap for the two seasons 2018 and 2019 respectively. Results indicated that the use of nano gel pheromone for the first time in field improved the trap catchability to RPW adults by 22.51 and 18.30% of total number of RPW adults captured throw out the two successive seasons respectively. In addition, there was no significant difference between the total numbers of RPW adults collected by the two tested type of traps over the two successive seasons. Furthermore, the sex ratio between males and females of total collected RPW adults found to be1: 1.43 and 1: 1.94 at 2018 and 2019 respectively.

Experimentos de campo foram realizados na terra recuperada a leste da estrada do deserto de Cairo-Alexandria, vila de Wardan, província de Giza, Egito, para avaliar o impacto do uso de feromônio de nano géis pela primeira vez na atração de adultos RPW por armadilhas de feromônio comparado ao controle que é o feromônio normal durante duas temporadas sucessivas em 2018 e 2019. Além disso, este estudo teve como objetivo comparar a eficácia de dois tipos de armadilha, armadilha tradicional (tipo 1) e armadilha de funil seco (tipo 2) na captura de RPW adultos. Os resultados revelaram que as armadilhas de nano gel de feromônio atraíram significativamente mais adultos, com uma média de (4,26 e 3,56) adultos/armadilha e total de (55,33 e 46,33) adultos/armadilha em comparação ao controle com uma média (2,69 e 2,46) e total de (35.00 e 32.00) adultos/armadilha para as duas temporadas 2018 e 2019, respectivamente. Os resultados indicaram que o uso de feromônio nano gel pela primeira vez em campo melhorou a capturabilidade de armadilhas para adultos com RPW em 22,51 e 18,30% do número total de adultos com RPW capturados durante as duas estações sucessivas, respectivamente. Além disso, não houve diferença significativa entre o número total de adultos RPW coletados pelos dois tipos de armadilhas testados ao longo das duas estações sucessivas. Além disso, a proporção sexual entre homens e mulheres do total de adultos coletados de RPW foi de 1: 1,43 e 1: 1,94 em 2018 e 2019, respectivamente.

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Different synthetic strategies were tested for the incorporation of galactose molecules on thermoresponsive nanogels owing to their affinity for receptors expressed in cancer cells. Three families of galactose-functionalized poly(N-vinylcaprolactam) nanogels were prepared with the aim to control the introduction of galactose-moieties into the core, the core-shell interface and the shell. First and second of the above mentioned, were prepared via surfactant free emulsion polymerization (SFEP) by a free-radical mechanism and the third one, via SFEP/reversible addition-fragmentation chain transfer (RAFT) polymerization. Synthetic recipes for the SFEP/free radical method included besides N-vinylcaprolactam (NVCL), a shell forming poly(ethylene glycol) methyl ether methacrylate (PEGMA), while the galactose (GAL) moiety was introduced via 6-O-acryloyl-1,2,:3,4-bis-O-(1-methyl-ethylidene)-α-D-galactopiranose (6-ABG, protected GAL-monomer): nanogels I, or 2-lactobionamidoethyl methacrylate (LAMA, GAL-monomer): nanogels II. For the SFEP/RAFT methodology poly(2-lactobionamidoethyl methacrylate) as GAL macro-chain transfer agent (PLAMA macro-CTA) was first prepared and on a following stage, the macro-CTA was copolymerized with PEGMA and NVCL, nanogels III. The crosslinker ethylene glycol dimethacrylate (EGDMA) was added in both methodologies for the polymer network construction. Nanogel's sizes obtained resulted between 90 and 370 nm. With higher content of PLAMA macro-CTA or GAL monomer in nanogels, a higher the phase-transition temperature (TVPT) was observed with values ranging from 28 to 46 °C. The ρ-parameter, calculated by the ratio of gyration and hydrodynamic radii from static (SLS) and dynamic (DLS) light scattering measurements, and transmission electron microscopy (TEM) micrographs suggest that core-shell nanogels of flexible chains were obtained; in either spherical (nanogels II and III) or hyperbranched (nanogels I) form.

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Abstract Field experiments were carried out in the reclaimed land east of Cairo-Alexandria Desert Road, Village of Wardan, Giza Governorate, Egypt, to evaluate the impact of using nano-gels pheromone for the first time on the attraction of the RPW adults by pheromone traps compared to the control which is normal pheromone during two successive seasons in 2018 and 2019. Also, this study aimed to compare the efficacy of two types of trap, traditional trap (type 1) and dry funnel trap (type 2) in capturing of RPW adults. Results revealed that the nano gel pheromone traps attracted significantly more adults with an average of (4.26 and 3.56) adults/trap and total of (55.33 and 46.33) adults/trap compared to control with an average (2.69 and 2.46) and total of (35.00 and 32.00) adults/trap for the two seasons 2018 and 2019 respectively. Results indicated that the use of nano gel pheromone for the first time in field improved the trap catchability to RPW adults by 22.51 and 18.30% of total number of RPW adults captured throw out the two successive seasons respectively. In addition, there was no significant difference between the total numbers of RPW adults collected by the two tested type of traps over the two successive seasons. Furthermore, the sex ratio between males and females of total collected RPW adults found to be1: 1.43 and 1: 1.94 at 2018 and 2019 respectively.

Resumo Experimentos de campo foram realizados na terra recuperada a leste da estrada do deserto de Cairo-Alexandria, vila de Wardan, província de Giza, Egito, para avaliar o impacto do uso de feromônio de nano géis pela primeira vez na atração de adultos RPW por armadilhas de feromônio comparado ao controle que é o feromônio normal durante duas temporadas sucessivas em 2018 e 2019. Além disso, este estudo teve como objetivo comparar a eficácia de dois tipos de armadilha, armadilha tradicional (tipo 1) e armadilha de funil seco (tipo 2) na captura de RPW adultos. Os resultados revelaram que as armadilhas de nano gel de feromônio atraíram significativamente mais adultos, com uma média de (4,26 e 3,56) adultos/armadilha e total de (55,33 e 46,33) adultos/armadilha em comparação ao controle com uma média (2,69 e 2,46) e total de (35.00 e 32.00) adultos/armadilha para as duas temporadas 2018 e 2019, respectivamente. Os resultados indicaram que o uso de feromônio nano gel pela primeira vez em campo melhorou a capturabilidade de armadilhas para adultos com RPW em 22,51 e 18,30% do número total de adultos com RPW capturados durante as duas estações sucessivas, respectivamente. Além disso, não houve diferença significativa entre o número total de adultos RPW coletados pelos dois tipos de armadilhas testados ao longo das duas estações sucessivas. Além disso, a proporção sexual entre homens e mulheres do total de adultos coletados de RPW foi de 1: 1,43 e 1: 1,94 em 2018 e 2019, respectivamente.

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Introduction: The development of more efficacious vaccines, especially subunit vaccines administered via non-invasive routes, is a priority in vaccinology. Nanogels are materials that can meet the requirements to serve as efficient vaccine delivery vehicles (in terms of thermo-sensitivity, biocompatibility, and pH-responsiveness; among others); thus there is a growing interest in exploring the potential of nanogels for vaccine development. Areas covered: Herein, a critical analysis of nanogel synthesis methodologies is presented and nanogel-based vaccines under development are summarized and placed in perspective. Promising vaccine candidates based on nanogels have been reported for cancer, obesity, and infectious diseases (mainly respiratory diseases). Some of the candidates were administered by mucosal routes which are highly attractive in terms of simple administration and induction of protective responses at both mucosal and systemic levels. Expert opinion: The most advanced models of nanogel-based vaccines comprise candidates against cancer, based on cholesteryl pullulan nanogels evaluated in clinical trials with promising findings; as well as some vaccines against respiratory pathogens tested in mice thus far. Nonetheless, the challenge for this field is advancing in clinical trials and proving the protective potential in test animals for many other candidates. Implementing green synthesis approaches for nanogels is also required.

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Introduction: Lower respiratory tract infections are the fourth cause of death worldwide and pneumococcus is the leading cause of pneumonia. Nonetheless, existing pneumococcal vaccines are less effective against pneumonia than invasive diseases and serotype replacement is a major concern. Protein antigens could induce serotype-independent protection, and mucosal immunization could offer local and systemic immune responses and induce protection against pneumococcal colonization and lung infection. Areas covered: Immunity induced in the experimental human pneumococcal carriage model, approaches to address the physiological barriers to mucosal immunization and improve delivery of the vaccine antigens, different strategies already tested for pneumococcal mucosal vaccination, including live recombinant bacteria, nanoparticles, bacterium-like particles, and nanogels as well as, nasal, pulmonary, sublingual and oral routes of vaccination. Expert opinion: The most promising delivery systems are based on nanoparticles, bacterial-like particles or nanogels, which possess greater immunogenicity than the antigen alone and are considered safer than approaches based on living cells or toxoids. These particles can protect the antigen from degradation, eliminating the refrigeration need during storage and allowing the manufacture of dry powder formulations. They can also increase antigen uptake, control release of antigen and trigger innate immune responses.

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Stimuli-responsive polymeric nanogels have been proposed as nanocarriers of cisplatin to maximize its effect for cancer treatment. In this work, a comparative study between anionic core nanogels (ACN) and cationic core nanogels (CCN), both with PEGylated shells, has been performed. The nanogels were synthesized with different cross-linked cores: CCN with poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) and ACN with poly(2-methacryloyloxi benzoic acid) (P2MBA). Cisplatin chelate formation with carboxylic acids (ACN) or metal coordination with the amine groups (CCN) leads to a high loading of cisplatin into the nanocarriers. The nanocarriers ability to contain and modulate the supply of cisplatin was tested according to the pH of the medium, in which ACN efficiently released the drug at a typical pH value of a tumor tissue (pH = 6.8) while CCN only releases the drug at more acidic, endosome like, conditions (pH = 5). The effect of drug-free nanogels on cell lines NCI-H1437 (non-small cell lung carcinoma) was evaluated, showing biocompatibility at all concentrations studied (30-400 µg/mL) for both ACN and CCN. However, the survival percentage of the cells in contact with cisplatin-loaded nanogels were dependent on the dose, the time of contact and the type of nanogel. Cisplatin loaded CCN induced lower cell viability after 48 h of contact. Fluorescence microscopy showed a viable internalization of the CCN nanogels, this was confirmed by flow cytometry in which 37.8% of cells contained drug loaded CCNs after 30 min of contact, representing a more effective nanocarrier for cisplatin to this cell-line.

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The current limitations in the use of nanocarriers to treat constantly evolving diseases call for the design of novel and smarter drug delivery systems (DDS). Nanogels (NGs) are three-dimensional crosslinked polymers with dimensions on the nanoscale and with a great potential for use in the biomedical field. Particular interest focuses on their application as DDS to minimize severe toxic effects and increase the therapeutic index of drugs. They have recently gained attention, since they can include responsive modalities within their structure, which enable them to excerpt a therapeutic function on demand. Their bigger sizes and controlled architecture and functionality, when compared to non-crosslinked polymers, make them particularly interesting to explore novel modalities to cross biological barriers. The present review summarizes the most significant developments of NGs as smart carriers, with focus on smart modalities to cross biological barriers such as cellular membrane, tumor stroma, mucose, skin, and blood brain barrier. We discuss the properties of each barrier and highlight the importance that the NG design has on their capability to overcome them and deliver the cargo at the site of action.

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Smart nanomaterials can selectively respond to a stimulus and consequently be activated in specific conditions, as a result of their interaction with electromagnetic radiation, biomolecules, or pH change. These nanomaterials are produced through distinct routes and can be used in artificial skin, drug delivery, and other biomedical applications. Here, we report on the fabrication of an antibacterial nanogel formed by aniline- and chitosan-containing silver nanoparticles (AgNp's), with an average size of 78 ± 19 nm. The AgNp nanogel release was triggered by light at 405 nm. Specifically, the electronic energy vibration resulting from the interaction of the irradiation with the AgNp surface plasmon breaks the hydrogen bonds of the nanogels and releases AgNp's. To understand the perturbation of AgNp-nanogels against bacteria, membrane model studies were performed using the main components of the cell membrane of Escherichia coli (E. coli), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE). DPPG has more influence on the incorporation of the nanoparticles on the cell membrane due to the electrostatic interaction between the nanoparticle surface and lipid charged groups. The results indicate new possibilities for designing smart antibacterial photoresponsive nanogels with enhanced optical and antibacterial properties to increase E. coli death.

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Introduction: Lower respiratory tract infections are the fourth cause of death worldwide and pneumococcus is the leading cause of pneumonia. Nonetheless, existing pneumococcal vaccines are less effective against pneumonia than invasive diseases and serotype replacement is a major concern. Protein antigens could induce serotype-independent protection, and mucosal immunization could offer local and systemic immune responses and induce protection against pneumococcal colonization and lung infection. Areas covered: Immunity induced in the experimental human pneumococcal carriage model, approaches to address the physiological barriers to mucosal immunization and improve delivery of the vaccine antigens, different strategies already tested for pneumococcal mucosal vaccination, including live recombinant bacteria, nanoparticles, bacterium-like particles, and nanogels as well as, nasal, pulmonary, sublingual and oral routes of vaccination. Expert opinion: The most promising delivery systems are based on nanoparticles, bacterial-like particles or nanogels, which possess greater immunogenicity than the antigen alone and are considered safer than approaches based on living cells or toxoids. These particles can protect the antigen from degradation, eliminating the refrigeration need during storage and allowing the manufacture of dry powder formulations. They can also increase antigen uptake, control release of antigen and trigger innate immune responses.

RESUMO

The aim of this study was to synthesize chitosan hydrogels, in macro- and nano-size, grafted with N-vinylcaprolactam (NVCL) using gamma radiation, and evaluate their potential application as a drug delivery system, using 5-fluorouracil (5-FU) as a model drug. The effect of dose and monomer concentration in the grafting process was studied, and the materials were characterized by FTIR, TGA, DLS, SEM and AFM. Higher grafting percentages were observed for the nanogels system. Although both the grafted macro- and nanogels, (net-CS)-g-NVCL, showed a response to pH (4.75) and temperature (31-33°C), the nanogels showed a better swelling response to both stimuli because of their higher surface area. Both systems were able to load 5-FU in small amounts (2-3.5mgg-1) and the release was sustained for more than 12h, showing that the modified macro and nanogels can be a potential alternative for the administration of drugs.