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Este estudo avaliou a eficácia in vitro e in vivo de mantas de nanofibras (NF) de policaprolactona (PCL) incorporadas com nistatina (NIS) no tratamento da estomatite protética (EP) em modelos animais. NF foram sintetizadas com diferentes concentrações de NIS, totalizando quatro soluções: PCL puro, PCL/NIS 0,045 g, PCL/NIS 0,090 g e PCL/NIS 0,225 g. A liberação da NIS foi analisada por espectroscopia Ultravioleta-Visível. A capacidade das mantas de inibirem o biofilme de Candida albicans, principal fator etiológico da EP, dividindo-se cinco grupos (N=5) compostos por um grupo com controle de células de C. albicans e com PCL puro, além das três concentrações de NIS. A seguir, foi analisada a viabilidade celular em queratinócitos humanos (HaCat) por meio do teste colorimétrico de resazurina. Cinco grupos foram divididos (N=10): controle celular, PCL puro e as três concentrações de NIS. Em modelos animais de ratos Wistar albinos (N=18), dispositivos palatinos (DP) de resina acrílica foram confeccionados simulando próteses totais e utilizados para a indução da EP. Para isso, DP contaminados com C. albicans foram cimentados na região molar da cavidade bucal dos animais e permaneceram em boca por 48 h. Após esse período, os DP foram removidos e os animais foram divididos em três grupos: (C) controle; (B1) com tratamento por mantas de PCL/NIS 0,045 g e (B2) PCL/NIS 0,225 g, com N=6. Então novos DP, livres de contaminação, foram cimentados na cavidade oral dos animais e permaneceu por mais 48 h. Após esse período, os animais foram eutanasiados, a contagem de UFC/ mL foi realizada e os palatos foram coletados para a análise histológica. A curva padrão de NIS obtida apresentou R2 de 0,99. As três concentrações de NF apresentaram liberação de NIS, com pico no tempo de 6 h e valores de 66,26 µg/ mL para PCL/NIS 0,045 g, de 333,87 µg/ mL para PCL/NIS 0,090 g e 436,51 µg/ mL para PCL/NIS 0,225 g, constantes até o fim do experimento. Os grupos com NIS reduziram em 2,5 log10 de crescimento do biofilme fúngico em relação aos grupos sem tratamento, Controle e PCL, sem diferença estatística significativa. Não foi observada citotoxicidade nas células HaCat, com viabilidade celular de 93,7% para PCL/NIS 0,045 g, 72,6% para PCL/NIS 0,090 g e 72,4% para PCL/NIS 0,225 g. A indução da EP nos três grupos foi possível e, porém, sem redução significativa na contagem de UFC/ mL de C. albicans nos grupos B1 e B2. Na análise histológica do grupo C pôde-se observar infiltração de hifas de Candida na camada queratinizada, presença de células inflamatórias formando micro abscessos e um discreto infiltrado inflamatório no tecido conjuntivo subjacente ao epitélio infectado. Nos grupos B1 e B2 não foram encontradas alterações epiteliais, concluindo-se que as NF demonstraram atividade antifúngica in vitro e foram efetivas na prevenção da penetração de hifas no tecido palatino de animais com DP (AU)
This study evaluated the in vitro and in vivo efficacy of nanofiber (NF) mats of polycaprolactone (PCL) incorporated with nystatin (NIS) in the treatment of denture stomatitis (DS) in animal models. NFs were synthesized with different concentrations of NIS, totaling four solutions: pure PCL, PCL/NIS 0.045 g, PCL/NIS 0.090 g, and PCL/NIS 0.225 g. The release of NIS was analyzed by Ultraviolet-Visible spectroscopy. The ability of the mats to inhibit Candida albicans biofilm, the main etiological factor of DS, was assessed by dividing five groups (N=5) composed of a group with C. albicans cell control and with pure PCL, in addition to the three concentrations of NIS. Next, cell viability in human keratinocytes (HaCat) was analyzed using the resazurin colorimetric test. Five groups were divided (N=10): cell control, pure PCL, and the three concentrations of NIS. In albino Wistar rat animal models (N=18), palatal devices (PD) made of acrylic resin were fabricated to simulate total prostheses and used to induce DS. For this, PD contaminated with C. albicans were cemented in the molar region of the animals' oral cavity and remained in the mouth for 48 hours. After this period, the PDs were removed, and the animals were divided into three groups: (C) control; (B1) treated with PCL/NIS 0.045 g mats, and (B2) PCL/NIS 0.225 g, with N=6. Then new, uncontaminated PDs were cemented in the animals' oral cavity and remained for another 48 hours. After this period, the animals were euthanized, UFC/ mL counts were performed, and the palates were collected for histological analysis. The standard NIS curve obtained showed an R2 of 0.99. The three concentrations of NF showed NIS release, with a peak at 6 h and values of 66.26 µg/ mL for PCL/NIS 0.045 g, 333.87 µg/ mL for PCL/NIS 0.090 g, and 436.51 µg/ mL for PCL/NIS 0.225 g, remaining constant until the end of the experiment. The groups with NIS reduced fungal biofilm growth by 2.5 log10 compared to the untreated groups, Control and PCL, with no significant statistical difference. No cytotoxicity was observed in HaCat cells, with cell viability of 93.7% for PCL/NIS 0.045 g, 72.6% for PCL/NIS 0.090 g, and 72.4% for PCL/NIS 0.225 g. Induction of DS in the three groups was possible; however, there was no significant reduction in UFC/ mL counts of C. albicans in groups B1 and B2. Histological analysis of group C revealed infiltration of Candida hyphae in the keratinized layer, presence of inflammatory cells forming micro abscesses, and a discreet inflammatory infiltrate in the connective tissue underlying the infected epithelium. No epithelial alterations were found in groups B1 and B2, concluding that NFs demonstrated in vitro antifungal activity and were effective in preventing hyphal penetration into palatal tissue in animals with PD.(AU)
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Estomatite sob Prótese , Candida albicans , NistatinaRESUMO
Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.
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Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.
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@#Tumor is the main cause of global related death.Although the existing treatment methods have made significant progress,the lack of specificity and low bioavailability are still the challenge in the treatment.Exosomes are lipid bilayer extracellular vesicles that were released in the range of 30—150 nm when a multi vesicular body(MVB) fuses with plasma membrane,which are important mediators of intercellular communication,and can transport cellular components such as proteins,lipids and nucleic acids to neighboring or distant cells,thus changing the role of recipient cells.Exosomes have been used as natural nano-carriers for drug delivery.After being loaded with antitumor drugs,they can be delivered to the focus for targeted treatment of various tumors,and the therapeutic effect is good.In this paper,the advantages of exosomes-based antitumor drug delivery system,drug loading methods and the research progress of exosomes from different cells in cancer treatment are reviewed so as to provide important basis for the targeted treatment of cancer.
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Osimertinib is an irreversible third representative epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of non-small cell lung cancer (NSCLC) with T790M resistance and classical EGFR mutations. However, the therapeutic effectiveness of osimertinib is limited by acquired drug-resistance, poor water solubility and low tumor accumulation rates. Nanodrug delivery systems can increase the solubility and stability of drugs, prolong the blood circulation time of drugs, improve the uptake rate of cells, promote drug accumulation in tumor tissues, and improve drug resistance. Thus, they are effective in overcoming the limitations of traditional targeted drugs. In this study, we reviewed the mechanism of action of the third-generation EGFR-TKI osimertinib, focused on research advances in osimertinib nanodrug delivery systems against NSCLC, and explored the challenges and future development direction in this field.
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Diseases of ocular fundus are the leading causes of severe vision impairment or even blindness in patients worldwide, and the medical treatments are seriously limited by the difficulty of therapeutic drugs entering the fundus due to the various physiological barriers. Nano-drug delivery systems, with their nanoscale size and large surface area, can be loaded with therapeutic drugs of different physicochemical properties and modified with various surface active substances, which can not only improve the solubility and penetration of the drugs, but also protect biologic drugs from degradation and improve the biological safety and bioavailability, as well as deliver therapeutic drugs to specific ocular targets. All of these make the therapeutic potential enormous. Currently, more and more studies have been carried out to take advantage of nanomaterials for the treatment of different fundus diseases, including neurodegenerative diseases, fundus neovascularization, endophthalmitis and fundus tumors. This review analyzes the challenges and barriers faced by different routes of drug administration in the treatment of fundus diseases, the physicochemical properties of common nano-drug delivery systems that have been studied in related fields, and further summarizes the progress, advantages, limitations, and future directions of the application of various nano-drug delivery systems for the treatment of ocular fundus diseases in recent years.
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Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca2+-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca2+ with an immune-regulating ability and CO2 with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.
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Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.
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Chinese materia medica has a wide range of clinical applications， but it has many active ingredients with different physicochemical properties， and the target organs， action pathways and mechanisms for different ingredients to exert their efficacy are not the same. Therefore， it is difficult to design and develop a co-delivery system loading multiple components of Chinese materia medica to maximize the synergistic therapeutic efficiency. Based on the characteristics of effectiveness and functionality of active ingredients， the strategies for multi-component co-delivery of Chinese materia medica can be categorized into two types：firstly， based on the effectiveness of active ingredients， new carriers such as liposomes， nanoparticles can be constructed to load multi-components of Chinese materia medica. secondly， based on the functionality of some active ingredients of Chinese materia medica， they are employed in the construction of co-delivery system， which can give play to the dual characteristics of their own efficacy and preparation functions. In this paper， we summarized the relevant research progress of the above two types of multi-component co-delivery strategies， and mainly discussed the pharmaceutical functions of the active ingredients in co-delivery systems， in order to find a more suitable multi-component co-delivery strategy， promoting the design and development of new delivery systems of Chinese materia medica.
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Uveitis, a complex ocular disorder with numerous etiologies, can result from infection, autoimmune, and various physicochemical and mechanical injury factors. The treatment of this disease is difficult, and failure to receive timely and effective treatment can often lead to blindness. With the deepening of people's understanding of uveitis and its related mechanisms, various new sustained-release drug delivery systems for uveitis have been studied. However, due to the existence of various anatomical and physiological barriers in the eye, there are multiple obstacles to the sustained release treatment of uveitis. In this paper, the main research results in this field in recent years are reviewed, and the innovations and limitations of various new sustained-release drug delivery systems are discussed in order to provide new ideas for the sustained-release drug delivery treatment of uveitis in the future. These new sustained-release drug delivery systems will help to completely change the traditional treatment mode of uveitis with side effects and poor compliance in the future, bringing longer targeted sustained release and less toxic reactions.
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Oral administration is the most convenient way of drug delivery， but due to the existence of intestinal barrier， the oral bioavailability of drugs is generally low， especially for drugs with low water solubility， poor permeability and macromolecules. For decades， researchers have demonstrated that nano-delivery system is one of the most effective strategies to solve this problem， but nano-delivery systems have shown limited improvement in the oral bioavailability of drugs. Therefore， researchers have proposed to use transporter-mediated nano-delivery systems to promote the oral absorption of drugs. The intestinal tract were highly expressed as a transporter for ingesting various nutrients（such as glucose， oligopeptides and bile acids）， which was an excellent target of oral drug delivery system. Its substrate were modified on the nano-delivery system， and the loaded drugs could cross the intestinal barrier and enter the systemic circulation more efficiently through the targeting effect of transporters. At present， more and more evidences supported the potential of transporters in the field of oral drug delivery system. Therefore， this paper reviewed the research on intestinal transporters-mediated nano-delivery system to promote oral absorption of drugs， including the distribution of intestinal transporters， three strategies of transporter substrate modification， the transport properties of different types of transporters and their effects of mediating the nano-delivery system for promoting the oral absorption of drugs or treating diseases， with the aim of providing an important theoretical reference for the development of intestinal targeted nano-delivery systems.
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ABSTRACT Hydrogels are gaining widespread popularity in the biomedical field due to their extraordinary properties, such as biocompatibility, biodegradability, zero toxicity, easy processing, and similarity to physiological tissue. They have applications in controlled drug release, wound dressing, tissue engineering, and regenerative medicine. Among these applications, hydrogels as a controlled drug delivery system stands out, which releases active substances in precise amounts and at specific times. To explore the latest advances in the design of hydrogels, a literature review of articles published in indexed scientific journals, in Scopus and Science Direct, was carried out. This review aimed to discover and describe the most innovative hydrogel research with applications in the biomedical field; hydrogels synthesized with polymers of different origins were selected, such as; i. Natural (dextran, agarose, chitosan, etc.); ii. Synthetic (polyacrylamide, polyethylene glycol, polyvinyl alcohol, etc.); iii. Composites (interpenetrants, hybrid crosslinkers, nanocomposites, etc.). Comparative analysis revealed that hydrogels with composite materials show the most promise. These composite hydrogels combine the advantages of different polymers or incorporate additional components, offering enhanced properties and functionalities. In summary, hydrogels are versatile biomaterials with immense potential in biomedicine. Their unique properties make them suitable for diverse applications. However, innovative designs and formulations must continue to be explored to further advance the capabilities of hydrogels and expand their biomedical applications.
RESUMEN Los hidrogeles están ganando una extensa popularidad en el campo biomédico gracias a que presentan propiedades extraordinarias como biocompatibilidad, biodegradabilidad, nula toxicidad, fácil procesamiento, y similitud con el tejido fisiológico. tienen aplicaciones en la liberación controlada de fármacos, el vendaje de heridas, la ingeniería de tejidos y la medicina regenerativa. Entre estas aplicaciones, destaca el uso de hidrogeles como sistema de administración controlada de fármacos, que liberan sustancias activas en cantidades precisas y en momentos concretos. Para explorar los últimos avances en el diseño de hidrogeles, se realizó una revisión bibliográfica de artículos publicados en revistas científicas indexadas, en Scopus y Science Direct. El objetivo de esta revisión fue descubrir y describir las investigaciones de hidrogeles más innovadoras con aplicaciones en el campo biomédico, se seleccionaron hidrogeles sintetizados con polímeros de diferente índole como; i. Naturales (dextrano, agarosa, quitosano, etc.); ii. Sintéticos (poliacrilamida, polietilenglicol, alcohol polivinílico, etc); iii. Compuestos (interpenetrantes, reticulantes híbridos, nanocompuestos, etc.). El análisis comparativo reveló que los hidrogeles que utilizan materiales compuestos son los más prometedores. Estos hidrogeles compuestos combinan las ventajas de distintos polímeros o incorporan componentes adicionales, ofreciendo propiedades y funcionalidades mejoradas. En resumen, los hidrogeles son biomateriales versátiles con un inmenso potencial en biomedicina. Sus propiedades únicas los hacen adecuados para diversas aplicaciones, sin embargo, se debe seguir explorando diseños y formulaciones innovadores para seguir avanzando en las capacidades de los hidrogeles y ampliar sus aplicaciones biomédicas.
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With the advancement in the study of keratoconjunctivitis sicca and the scope of its treatment, punctal plugs are being widely used for the therapeutic management of dry eye disease. With the emergence of 3D printing in medicine, 3D printing of punctal plugs that have an inbuilt drug delivery system and also that can be personalized from patient to patient according to their punctum size can be a great therapeutic option. Another benefit of the device is that its printing takes a short period of time and is cost-effective. This study aimed at making an open source design and 3D printing an efficient model of a punctal plug with an inbuilt drug delivery system that can be eventually used for the treatment of various ocular diseases that require frequent drug instillation or blockage of the nasolacrimal pathway. The 3D design for the punctal plug was made using the open source application, FreeCAD, and slicing was done using the application ChituBox. After that, the plugs were printed using the LCD printer Crealty LD-002R. The material used was resin that was compatible with the Crealty LD-002R. Punctal plugs with satisfactory results were printed using the LCD printer. The punctal plugs showed suitable structure and were also easily reproduced in the 3D printer without any complications or setbacks.
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Objetivos: El propósito de esta investigación fue determinar el nivel de conocimiento, creencias, percepción y practicas asociadas al consumo de cigarrillos electrónicos en los estudiantes universitarios (UASD), recinto Santiago, República Dominicana. Cada estudiante firmó un consentimiento informado certificando que éste respondió cada pregunta realizada por el entrevistador de manera voluntaria. El método de recolección de los datos fue mediante entrevistas, las cuales fueron grabadas por los entrevistadores. La muestra fue de 53 entrevistas, 48 individuales y 5 grupos focales, la misma se tomó hasta alcanzar el punto de saturación de cada pregunta, es decir cuando todas las respuestas se tornaron repetitivas. Materiales y métodos: Se realizó un estudio cualitativo de tipo fenomenológico y de fuentes primarias en el período mayo-agosto del año 2019 en la universidad privada Pontificia Universidad Católica Madre y Maestra (PUCMM) y la universidad pública Universidad Autónoma de Santo Domingo. (UASD), campus Santiago, República Dominicana. El método de recolección de datos se realizó a través de entrevistas, las cuales fueron grabadas por los entrevistadores. Cada estudiante entrevistado firmó un consentimiento informado certificando que respondió voluntariamente a cada pregunta formulada por el entrevistador. La muestra estuvo compuesta por 53 entrevistas, 48 personas y cinco grupos focales. Las entrevistas se realizaron hasta llegar al punto de saturación de cada pregunta, que es cuando todas las respuestas se volvieron repetitivas. Resultados: El conocimiento que tiene los estudiantes universitarios sobre cigarrillo electrónico (CE), es pobre, desde su funcionamiento, partes, sustancias e incluso las posibles complicaciones que puede traer a la salud, tanto en la Pontificia Universidad Católica Madre y Maestra (PUCMM) como en la Universidad Autónoma de Santo Domingo (UASD), pero es más notable en la universidad pública. Por otro lado, muchos perciben el CE, como una alternativa del uso de tabaco, que posee diversidad de sabores, olor agradable, atractivo, práctico y capaz de ofrecer relajación. En cuanto a la actitud hacia el dispositivo, en PUCMM exhibe un mayor nivel de rechazo con respecto al uso. Es importante mencionar, que mayoría de los entrevistados son o alguna vez fueron usuarios de este, no obstante, no lo recomiendan en gran medida, ya que asumen que puede causar daño y ser adictivo, aunque en menor medida al cigarrillo convencional. La población más susceptible a su uso, son los jóvenes y el sexo masculino, aunque las féminas se han ido sumando de manera significativa. De igual modo, se logró apreciar las grandes influencias que mueven a los jóvenes a su consumo, incluyendo, las redes sociales, familia, amigos, en general el entorno en que se rodean. Conclusión: Concluimos que los estudiantes universitarios carecen de conocimiento con respecto al cigarrillo electrónico, tanto en el funcionamiento, sustancias y complicaciones para la salud. Muchos observan al cigarrillo electrónico como un dispositivo para fumar con un olor agradable, por lo cual puede ser muy atractivo para los usuarios. Se logró apreciar el importante papel que juegan las influencias sociales para el uso del dispositivo, promovido por las redes sociales y relaciones cercanas. Otro problema en la sociedad actual es el uso de CE en menores de edad. Según los resultados existe una gran necesidad de intervención y educación, principalmente en los jóvenes.
Objective: The purpose of this research was to determine the level of knowledge, beliefs, perception, and practices associated with consuming electronic cigarettes among university students. Materials and methods: A qualitative study of phenome-nological type and from primary sources was carried out in the period of May-August of the year 2019 at the private university Pontificia Universidad Católica Madre y Mae-stra (PUCMM) and the public university Universidad Autónoma de Santo Domingo (UASD), Santiago campus, Dominican Republic. The data collection method was done through interviews, which the interviewers recorded. Each student interviewed signed an informed consent cer-tifying that they answered voluntarily each question asked by the interviewer. The sample consisted of 53 interviews, 48 individuals, and five focus groups. Interviews were done until reaching the saturation point of each question, which is when all the answers became repetitive. Results: University students' knowledge regarding elec-tronic cigarettes (EC) is poor. Knowledge regarding its mechanism, parts, substances, and possible complications to one's health, is scarce both in PUCMM and the UASD, but this is more notable at the public university. Addition-ally, many perceive EC as an alternative to tobacco use, the former, as per our study population, having a variety of fla-vors, a pleasant smell, being attractive, practical, and capa-ble of offering relaxation. Regarding the attitude towards the device, PUCMM exhibits a higher level of rejection regarding its use. It is essential to mention that most inter-viewees were once users of EC. However, they do not rec-ommend it to a great extent since they assume that it can cause harm and be addictive, although to a lesser extent than conventional cigarettes. The population most suscep-tible to its use are young people, including minors and the male gender, although females have been significantly increasing its use. Similarly, it was possible to appreciate the influences that greatly evoke the younger population's consumption, including social networks, family, friends, and the surrounding environment. Conclusion: We concluded that university students have insufficient knowledge regarding electronic cigarettes, both in their mechanism, substances, and health compli-cations. Most see electronic cigarettes as smoking devices with a pleasant smell, which can be very attractive to users. It was possible to observe the critical role played by social influences on the use of the device, promoted by social networks and close relationships. Another problem in cur-rent society is the use of CE in minors. According to the results, there is a great need for intervention and educa-tion, mainly among the younger generation.
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Humanos , Adolescente , Adulto , Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Estudantes , República Dominicana , Produtos do TabacoRESUMO
Several types of periodontal and peri-implant soft tissue defects require surgical treatment to reestablish function and aesthetics. However, local, and systemic factors can jeopardize tissue repair leading to unexpected outcomes and postoperative discomfort. In order to overcome this problem, new devices have been developed to improve surgical procedures outcomes and patient experience. The aim of the present study was to develop a new silk fibroin (SF)/chitosan (CH) film loaded with insulin as a drug delivery system to improve palatal donor area healing after free gingival graft harvesting for ridge preservation. For this, biomaterial development, characterization and in vitro assessment were performed to evaluate the new delivery system. In addition, 3- months outcomes from palatal wound healing following the use of the proposed delivery system were assessed through clinical, patient centered parameters, immunological, microbiological, and histological evaluations. Sixty-nine patients with indication of tooth extraction were enrolled into 3 groups: Control Group (C) (n=23): open wound on palatal mucosa followed by spontaneous healing; SF/CH Film (F) (n=23): open wound on palatal mucosa and silk fibroin film as dressing; Insulin-loaded SF/CH film (IF) (n=23): open wound on palatal mucosa and an insulin- loaded silk fibroin film as a delivery system. : It was verified some characteristics that are favorable to the oral environment, such as mechanical properties, swelling and permeability to water vapor. The biomaterial presented a standard of a controlled release system through diffusion with delivery stability in human saliva, along with an excellent biocompatibility with the absence of cytotoxicity and genotoxicity increasing cell viability in lineage cells (HaCat). F and IF promoted accelerated palatal wound closure on day 7 and 14 after surgery, as well as an early epithelialization, compared to the C group. Both films were capable to reduce pro-inflammatory cytokines (IL-6, TNF-α, IL-1ß) and modulate biomarkers correlated to tissue degradation/remodeling. Spontaneous healing microbiome reported higher genus/species with pathogenic role in the oral mucosa with reduction in health species following this profile until de end of the follow-up. A tendency of eubiosis was observed in F and IF groups throughout healing process. It seems that this new device has a promising application in oral cavity and positively influence wound healing. (AU)
Diversos tipos de defeitos mucogengivais requerem abordagem cirúrgica para o reestabelecimento funcional e estético. Porém, alterações locais e sistêmicas podem prejudicar o processo de reparo gerando resultados inesperados e desconforto ao paciente. Biomateriais vem sendo desenvolvidos para melhorar os resultados dos procedimentos cirúrgicos e a experiência clínica do paciente. O objetivo do presente estudo foi desenvolver um filme de fibroína de seda (FS) e quitosana (QT) carregado com insulina (INS), atuando como um sistema de liberação, para acelerar a cicatrização de feridas na área doadora palatina após procedimento de preservação de rebordo com uso de enxerto gengival livre. Para isso, foi executado o desenvolvimento, caracterização e avaliação in vitro do biomaterial. Ademais, o resultado de 3 meses do reparo das feridas palatinas foi verificado por meio de avaliações clínicas, imunológica, microbiológica, histológica, bem como parâmetros centrados no paciente. Sessenta e nove pacientes foram alocados aleatoriamente nos grupos Controle (C) (n=23): ferida aberta em palato seguido de cicatrização espontânea; Filme de FS/QT (F) (n=23): ferida aberta em palato associada ao filme na área doadora; Filme de FS/QT carregado com INS (IF) (n=23): ferida aberta em palato associada ao filme carregado com INS na área doadora. Verificou-se propriedades mecânicas, bem como de entumecimento e permeabilidade ao vapor de água, favoráveis ao meio bucal sem nenhuma alteração com a inclusão da INS. O dispositivo apresentou liberação controlada por meio de difusão com estabilidade em saliva humana. Excelente biocompatibilidade com ausência de cito e genotoxicidade foi observada em diversos tipos celulares aumentando a viabilidade celular em células de linhagem (HaCat). F e IF favoreceram um fechamento acelerado da ferida palatina aos 7 e 14 dias pós-injuria, assim como uma epitelização precoce destes comparado ao grupo C. F e IF reduziram citocinas pró-inflamatórias (IL6, TNF-α, IL-1ß) além de apresentarem função modulatória na quantificação de biomarcadores relacionados a degradação tecidual. O Grupo C apresentou gênero/espécies com potencial patogênico e redução de microrganismos relacionados a saúde mantendo este perfil aos 14 e 30 dias. Enquanto isso, uma tendência a eubiose foi observado em F e IF ao longo do processo de cicatrização. Deste modo, verifica-se a aplicação promissora do novo dispositivo na cavidade oral bem como capacidade de influenciar positivamente o reparo da mucosa oral. (AU)
Assuntos
Humanos , Cicatrização , Quitosana , Fibroínas , InsulinaRESUMO
Breast cancer is a malignant tumor that seriously threatens women’s health at present. Although surgical treatment is the most direct and effective， it is limited by many factors and needs to be assisted by other treatments. In addition to conventional radiotherapy， these adjuvant therapies also include chemotherapy， gene therapy， phototherapy and so on. However， the therapeutic agents used in these treatment methods have some limitations， such as poor water-solubility， instability and targeting. With the development of nano-technology， more and more researchers construct and study nano delivery system for breast tumor treatment， such as response system designed based on tumor microenvironment， temperature sensitive response system， nano delivery system based on specific proteins of tumor cell membrane， etc. The author summarizes the nano delivery system， and finds that these nano delivery systems can not only improve the water-solubility and stability of the therapeutic agents， but also accurately deliver them to the breast tumor site by targeted means， improve the efficacy and reduce toxic side effects， which provides new ideas for the treatment of breast cancer in the future.
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Extracellular vesicles (EVs) have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size, biocompatibility, and high stability. Herein, we demonstrate orange-derived extracellular vesicles (OEV) nanodrugs (DN@OEV) by modifying cRGD-targeted doxorubicin (DOX) nanoparticles (DN) onto the surface of OEV, enabling significantly enhancing tumor accumulation and penetration, thereby efficiently inhibiting the growth of ovarian cancer. The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells, which presented the average above 10-fold transcytosis effect compared with individual DN. It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway, thereby inducing the enhanced transcytosis. In particular, the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process. Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of the drug delivery system.
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In recent years, owing to the miniaturization of the fluidic environment, microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems (NDDSs) production processes. Compared with traditional methods, microfluidics improves the controllability and uniformity of NDDSs. The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs, including particle size, distribution and morphology, resulting in narrow particle size distribution and high drug-loading capacity. The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up. In this review, we provide a comprehensive summary of microfluidics-based NDDSs, including the fundamentals of microfluidics, microfluidic synthesis of NDDSs, and their industrialization. The challenges of microfluidics-based NDDSs in the current status and the prospects for future development are also discussed. We believe that this review will provide good guidance for microfluidics-based NDDSs.
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Malignant tumor is a major disease affecting human health. The nano-delivery system itself has a unique size effect and it can achieve tumor-targeted distribution of drug molecules, improve the therapeutic effect, and reduce the toxic and side effects on normal tissues and cells after functional modification. Patient-derived xenografts (PDX) models can be established by transplanting patient-derived cancer cells or small tumor tissue into immunodeficient mice directly. Compared with the tumor cell line model, this model can preserve the key features of the primary tumor such as histomorphology, heterogeneity, and genetic abnormalities, and keep them stable between generations. PDX models are widely used in drug evaluation, target discovery and biomarker development, especially providing a reliable research platform for the diagnosis and treatment evaluation of nano-delivery systems. This review summarizes the application of several common cancer PDX models in the evaluation of nano-delivery systems, in order to provide references for researchers to perform related research.
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Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.