Complexos polieletrólitos de quitosana e xantana carregados com ativos naturais e sintéticos: estudo físico/químico e microbiológico para aplicação de drug delivery / Polyelectrolyte complexes of chitosan and xanthan loaded with natural and synthetic actives: physicochemical and microbiological study for drug delivery application

A eficácia dos implantes osseointegrados é amplamente reconhecida na literatura científica. Contudo, infiltrações bacterianas na junção implante-pilar podem desencadear inflamação nos tecidos circundantes, contribuindo para a evolução de condições mais sérias, como a peri-implantite. O objetivo desse estudo foi produzir complexos polieletrólitos (PECs) de quitosana (Q) e xantana (X) em forma de membranas, carregá-las com ativos naturais e sintéticos antimicrobianos, caracterizálas estruturalmente e avaliá-las frente a degradação enzimática, cinética de liberação e ações antimicrobianas com finalidade de aplicação para drug delivery. Membranas de QX a 1% (m/v) foram produzidas em três proporções, totalizando doze grupos experimentais: QX (1:1); QX (1:2), QX (2:1), QX-P (com própolis) (1:1); QX-P (1:2); QX-P (2:1); QX-C (com canela) (1:1); QX-C (1:2); QX-C (2:1) e CLX (com clorexidina 0,2%) (1:1); CLX (1:2); CLX (2:1). Para os estudos de caracterização foram feitas análises da espessura em estado seco; análises morfológicas superficial e transversal em Microscopia Eletrônica de Varredura (MEV); análise estrutural de espectroscopia de infravermelho por transformada de Fourier (FTIR); análise de degradação por perda de massa sob ação da enzima lisozima; e análise da cinética de liberação dos ativos em saliva artificial. Para os testes microbiológicos, análises de verificação de halo de inibição e ação antibiofilme foram feitas contra cepas de Staphylococcus aureus (S. aureus) e Escherichia coli (E. coli). Os resultados demonstraram que a espessura das membranas variou conforme a proporção, sendo que o grupo QX (1:2) apresentou a maior média de 1,022 mm ± 0,2, seguida respectivamente do QX (1:1) com 0,641 mm ± 0,1 e QX (2:1) com 0,249 mm ± 0,1. Nas imagens de MEV é possível observar uma maior presença de fibras, rugosidade e porosidade nos grupos QX (1:2) e QX (1:1) respectivamente, e, no QX (2:1) uma superfície mais lisa, uniforme e fina. No FTIR foram confirmados os picos característicos dos materiais isoladamente, além de observar as ligações iônicas que ocorreram para formação dos PECs. Na análise de degradação, os grupos com ativos naturais adicionados tiveram melhores taxas de sobrevida do que os grupos QX. No teste de liberação, os grupos QX-P tiveram uma cinética mais lenta que os QX-C, cuja liberação acumulada de 100% foi feita em 24 h. Já nos testes do halo inibitório, somente os grupos CLX tiveram ação sobre as duas cepas, e os QX-P tiveram sobre S. aureus. Nas análises antibiofilme, os grupos CLX apresentaram as maiores taxas de redução metabólica nas duas cepas (± 79%); os grupos QX-P apresentaram taxas de redução similares em ambas as cepas, porém com percentual um pouco maior para E. coli (60- 80%) e os grupos QX-C tiveram grande discrepância entre as duas cepas: de 35 a 70% para S. aureus e 14 a 19% para E. coli. Pode-se concluir que, frente as análises feitas, o comportamento do material foi afetado diretamente pelos ativos adicionados a matriz polimérica. As proporções de Q ou X afetaram somente a espessura final. Quanto a aplicação proposta de drug delivery, os dispositivos apresentaram grande potencial, principalmente os grupos CLX e QX-P. (AU)

The effectiveness of osseointegrated implants is widely recognized in scientific literature. However, bacterial infiltrations at the implant-abutment interface may trigger inflammation in surrounding tissues, contributing to the development of more serious conditions, such as peri-implantitis. The aim of this study was to produce chitosan (Q) and xanthan (X) polyelectrolyte complexes (PECs) in the form of membranes, load and evaluate them for enzymatic degradation, release kinetics, and antimicrobial actions for drug delivery applications. QX membranes at 1% (w/v) were produced in three proportions, totaling twelve experimental groups: QX (1:1), QX (1:2), QX (2:1), QX-P (with propolis) (1:1), QX-P (1:2), QX-P (2:1), QX-C (with cinnamon) (1:1), QX-C (1:2), QX-C (2:1), and CLX (with 0.2% chlorhexidine) (1:1), CLX (1:2), CLX (2:1). Characterization studies included analyses of dry state thickness, surface and crosssectional morphology using Scanning Electron Microscopy (SEM), structural analysis by Fourier Transform Infrared (FTIR) spectroscopy, mass loss degradation analysis under lysozyme action, and active release kinetics analysis in artificial saliva. Microbiological tests included verification analyses of inhibition halos and antibiofilm action against strains of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Results showed that membrane thickness varied according to proportion, with group QX (1:2) presenting the highest average of 1.022 mm ± 0.2, followed by QX (1:1) with 0.641 mm ± 0.1, and QX (2:1) with 0.249 mm ± 0.1. SEM images showed greater presence of fibers, roughness, and porosity in groups QX (1:2) and QX (1:1) respectively, while QX (2:1) exhibited a smoother, more uniform, and thinner surface. FTIR confirmed characteristic peaks of the materials individually, besides showing ionic bonds formed for PECs. Degradation analysis revealed that groups with added natural actives had better survival rates than QX groups. In release tests, QX-P groups exhibited slower kinetics than QX-C, with 100% cumulative release achieved in 24 h. inhibitory halo tests, only CLX groups exhibited action against both strains, while QX-P acted against S. aureus. Antibiofilm analyses showed CLX groups with the highest metabolic reduction rates in both strains (± 79%); QX-P groups showed similar reduction rates in both strains, slightly higher for E. coli (60-80%), and QX-C groups had a significant discrepancy between strains: 35-70% for S. aureus and 14-19% for E. coli. In conclusion, material behavior was directly affected by added actives to the polymeric matrix. Proportions of Q or X only affected final thickness. Regarding proposed drug delivery applications, the devices showed great potential, especially CLX and QX-P groups.(AU)

Impact of e-cigarettes use on the oral health-related quality of life among young people in metropolitan Lima / Impacto en la calidad de vida relacionada a la salud oral del uso de cigarrillos electrónicos en los jóvenes de Lima metropolitana

Aim: To determine the effects of e-cigarette use on oral health-related quality of life (OHRQOL) in young people in Metropolitan Lima. Materials and Methods: This observational, analytical and cross-sectional study was performed with 189 individuals (age, 18­29 years) who used electronic cigarettes. The OHIP-Sp5 instrument was used to assess OHRQOL. Results: The use of e-cigarettes was higher among male participants (47.79%) than that among the female participants (26.32%). The mean OHRQOL scores of individuals who did and did not use e-cigarettes were 3.17 (2.26) and 3.12 (2.47), respectively These scores for people who did and did not use mouthwash were 2.92 (2.34) and 3.57 (2.43), respectively. Regarding orofacial pain 2.65% participants frequently re-ported "painful discomfort" and 7.41% of the young people presented such discomfort of orofacial aspect "frequently." Conclusions: Recording e-cigarette uses and frequency in patients' medical records is important, as well as incorporating educational strategies to reduce e-cigarette consumption and avoiding harmful effects on general health.

Objetivo: Evaluar el impacto en la calidad de vida relacionada a la salud oral del uso de cigarrillos electrónicos en los jóvenes de Lima Metropolitana. Materiales y Métodos: Se realizó un estudio observacional, analítico y transversal en un total de 189 jóvenes con edades comprendidas de 18 a 29 años que son usuarios de cigarrillos electrónicos. Para evaluar la calidad de vida relacionada a la salud oral se utilizó el instrumento "OHIP-Sp5". Resultados: Se determinó que los participantes del sexo masculino (47.79%) son los que más utilizan el cigarrillo electrónico en comparación a las participantes del sexo femenino (26.32%). Se observó una calidad de vida relacionada a la salud oral media de 3,17 (2,26) para los usuarios de cigarrillos electrónicos, mientras que para los no usuarios de cigarrillos electrónicos la media fue de 3,12 (2,47). Asimismo, para los que usan enjuagues bucales se encontró una media de 2.92(2.34), a diferencia de los que no hacían uso del mismo que presentaban peor calidad de vida relacionada con la salud oral con una media de 3.57(2.43). En cuanto a dolor orofacial el 2.65% de los participantes referían "molestias dolorosas" a menudo y el 7.41% de los jóvenes presentaban dicho disconfort de la apariencia orofacial "a menudo". Conclusión: El registro del uso y frecuencia del cigarrillo electrónico en la historia clínica de los pacientes es de suma importancia, así como incorporar estrategias educativas para reducir el consumo de los vapeadores y evitar efectos nocivos en la salud general.

Risco de exacerbação de asma em adolescentes usuários de dispositivos eletrônicos de liberação de nicotina: uma revisão sistemática e metanálise / Risk of asthma exacerbation in adolescent users of electronic nicotine delivery systems: a systematic review and meta-analysis

Este trabalho tem como objetivo investigar a associação entreo o uso dos cigarros eletrônicos e doenças pulmonares em adolescentes. Foi realizada uma revisão sistemática na base de dados PubMed. Os termos Mesh incluídos na busca foram "Electronic Nicotine Delivery Systems" e "Lung Diseases" e sinônimos no título e abstract, com o filtro de idade "child: birth - 18 years", para buscar artigos relacionados ao uso de cigarros eletrônicos e doenças pulmonares em adolescentes. Os critérios de elegibilidade consistiram em: usuários adolescentes, exposição ao cigarro eletrônico e doença pulmonar como desfecho. Os artigos foram selecionados por uma revisão pareada de maneira independente, primeiramente com a leitura dos títulos e resumos, seguida da leitura integral dos artigos selecionados, os quais foram analisados pela ferramenta New Castle-Ottawa quanto sua qualidade, e receberam entre 5 e 7 estrelas. Os dados encontrados foram extraídos para a realização da metanálise. Inicialmente foram encontrados 61 artigos, sendo seis considerados elegíveis, todos transversais e com aplicação de questionários. Na metanálise foi encontrada uma associação significativa entre o uso de cigarro eletrônico e exacerbação de asma (OR ajustado 1,44; IC 95% 1,17­1,76). Não foram encontrados estudos que avaliassem a associação do cigarro eletrônico e outras doenças pulmonares, incluindo EVALI (E-cigarette or Vaping product use-Associated Lung Injury), em adolescentes. Na metanálise foi encontrada uma associação significativa entre exacerbações de asma e uso de cigarros eletrônicos em adolescentes com asma crônica e nos previamente hígidos.

This study aims to investigate the association between electronic cigarette use and lung disease in adolescents. A systematic review was conducted in PubMed. We used the MeSH terms "Electronic Nicotine Delivery Systems" and "Lung Diseases" as well as synonyms in the title and abstract, with the age filter "child: birth - 18 years" to search for articles related to electronic cigarette use and lung disease in adolescents. The eligibility criteria consisted of adolescent users and exposure to e-cigarettes that resulted in lung disease. The articles were selected by independent assessment, reading first the titles and abstracts, then the full text of the selected articles. The Newcastle-Ottawa Scale was used to assess study quality, and the included studies received between 5 and 7 stars. Finally, the data were extracted for meta-analysis. Initially, 61 articles were found and 6 were considered eligible, all of which were cross-sectional and applied questionnaires. The meta-analysis found a significant association between electronic cigarette use and asthma exacerbation (adjusted OR 1.44 95% CI 1.17 - 1.76). However, no studies evaluated the association with other lung diseases, including electronic cigarette or vaping product use-associated lung injury in adolescents. The metaanalysis revealed a significant association between e-cigarette use and asthma exacerbation among adolescents with chronic asthma, as well as among their previously healthy peers.

Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe3O4@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe3O4@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe3O4@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T2 magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.

Effects of propofol and remifentanil in different TCI sequences on hypotension during induction of general anesthesia in hypertensive patients / 中华麻醉学杂志

Objective:To evaluate the effect of propofol and remifentanil in different target-controlled infusion(TCI) sequences on hypotension during induction of general anesthesia in hypertensive patients.Methods:A total of 132 patients with hypertension of both sexes, aged 50-75 yr, of American Society of Anesthesiologists Physical Status classificationⅡ or Ⅲ, with body mass index of 18-30 kg/m 2, scheduled for elective tracheal intubation under general anesthesia, were divided into 3 groups( n=44 each) using a random number table method: group C, PR group and RP group. In group C, propofol(target effect-site concentration 5 μg/ml) and remifentanil(target effect-site concentration 5 ng/ml) were simultaneously given by TCI. Propofol was given by TCI followed by TCI of remifentanil in PR group. Remifentanil was given by TCI followed by TCI of propofol in RP group. The development of hypotension was observed within 10 min after induction of general anesthesia, and the consumption of propofol, remifentanil and ephedrine, time of loss of consciousness, time of tracheal intubation and adverse reactions during the perioperative period were recorded. Results:Compared with group C, the incidence of hypotension during induction was significantly decreased, the consumption of propofol and ephedrine was decreased, and the BIS value was increased when consciousness disappeared, the time of loss of consciousness and time of tracheal intubation were prolonged, the BIS value was increased at loss of consciousness in PR group, and the consumption of ephedrine was significantly decreased, and the time of loss of consciousness and time of tracheal intubation were prolonged in RP group( P<0.05). Compared with PR group, the consumption of ephedrine was significantly decreased, and the time of loss of consciousness was prolonged in RP group( P<0.05). There was no significant difference in the incidence of responses to tracheal intubation, injection pain, bucking, inhibition ratio, postoperative delirium, postoperative nausea and vomiting, and intraoperative awareness during induction among the three groups( P>0.05). Conclusions:TCI of remifentanil followed by TCI of propofol can decrease the development of hypotension during induction of general anesthesia in hypertensive patients.

Applications and recent advances in transdermal drug delivery systems for the treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.

Advancing drug delivery to articular cartilage: From single to multiple strategies

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Research advances in peptide‒drug conjugates

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.

Plant-derived nanovesicles: Further exploration of biomedical function and application potential

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.

Research progress of tumor immunomodulation strategies based on nanodrug delivery system / 中国药科大学学报

@#Tumor immunotherapy is a therapeutic modality that uses immunological principles and methods to activate and enhance the body''s immune system to generate immune response for the removal of tumour cells. Many new immunotherapeutic agents have demonstrated effective anti-tumour capabilities, yet their clinical use is challenging due to the complex mechanisms of tumour immune escape. Meanwhile, these drugs would accumulate in different tissues and organs in the human body and be unable to achieve precise and specific targeting therapeutic effects, resulting in serious immune-related adverse effects, which greatly hinders the clinical potential of immunotherapy.Nanodrug delivery systems can deliver immunotherapeutic drugs to target tissues or specific immune cells precisely, thereby enhancing immune effects and reducing side effects.This paper reviews the research progress of nanodrug delivery systems in tumour immunotherapy in recent years based on the regulatory mechanism of the anti-tumour immune response, with a prospect of the challenges and development in this field.

Polymeric nanocarriers for nose-to-brain drug delivery in neurodegenerative diseases and neurodevelopmental disorders

Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system (CNS) and result in their damage and death. Neurodevelopmental disorders include intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes. The treatment of neurodegenerative and neurodevelopmental conditions, together affecting ∼120 million people worldwide, is challenged by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS. The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions. This pathway is more efficient for nanoparticles than for solutions, hence, the research on intranasal nano-drug delivery systems has grown exponentially over the last decade. Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility. This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions, the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them. Then, a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.

Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain

Abstract Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi, whose treatment has remained unsatisfactory for over 50 years, given that it is limited to two drugs. Benznidazole (BZN) is an efficient antichagasic drug used as the first choice, although its poor water-solubility, irregular oral absorption, low efficacy in the chronic phase, and various associated adverse effects are limiting factors for treatment. Incorporating drugs with such characteristics into nanostructured lipid carriers (NLC) is a promising alternative to overcome these limiting obstacles, enhancing drug efficacy and bioavailability while reducing toxicity. Therefore, this study proposed NLC-BZN formulations in different compositions prepared by hot-melt homogenization followed by ultrasound, and the optimized formulation was characterized by FTIR, DRX, DSC, and thermogravimetry. Biological activities included in vitro membrane toxicity (red blood cells), fibroblast cell cytotoxicity, and trypanocidal activity against epimastigotes of the Colombian strain of T. cruzi. The optimized NLC-BZN had a small size (110 nm), negative zeta potential (-18.0 mV), and high encapsulation (1.64% of drug loading), as shown by infrared spectroscopy, X-ray diffraction, and thermal analysis. The NLC-BZN also promoted lower in vitro membrane toxicity (<3% hemolysis), and 50% cytotoxic concentration (CC50) for NLC-BZN in L929 fibroblast cells (110.7 µg/mL) was twice the value as the free BZN (51.3 µg/mL). Our findings showed that the NLC-BZN had higher trypanocidal activity than free BZN against the epimastigotes of the resistant Colombian strain, and this novel NLC-BZN formulation proved to be a promising tool in treating Chagas disease and considered suitable for oral and parenteral administration

Selective photodynamic effects on cervical adenocarcinoma cells provided by F127 Pluronic®-based micelles modulating hypericin delivery

Abstract Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.

Prevalence and associated factors of experimentation with and current use of water pipes and electronic cigarettes among medical students: a multicentric study in Brazil / Prevalência de experimentação e uso atual de narguilé e cigarros eletrônicos e os fatores associados entre estudantes de medicina: estudo multicêntrico no Brasil

ABSTRACT Objective: To evaluate the prevalence of and factors associated with experimentation with and current use of water pipes and e-cigarettes among medical students. Methods: This was a cross-sectional multicentric study involving a convenience sample of students from medical schools in most Brazilian geographic regions. Information about experimentation with and current use of conventional cigarettes, water pipes, and e-cigarettes; beliefs and attitudes toward tobacco products; religiosity; and demographics were collected by means of an online structured questionnaire. We used descriptive statistics and logistic regression to analyze the association of those factors. Results: Our sample comprised 700 individuals from four Brazilian regions. Prevalence of experimentation with and current use of cigarettes, water pipes, and e-cigarettes were, respectively, 39.1% and 7.9%; 42.6% and 11.4%; and 13.1% and 2.3%. Water pipe experimentation was higher among those who had a sibling (adjusted OR = 2.64; 95% CI, 1.24-5.61) or friends (adjusted OR = 2.33; 95% CI, 1.63-3.31) who smoke. The same occurred regarding e-cigarette experimentation: siblings (adjusted OR = 2.76; 95% CI, 1.17-6.50) and friends (adjusted OR = 2.47; 95% CI, 1:45-4.22). Curiosity and scent/taste were the major reasons for water pipe use and e-cigarette experimentation. Although 93% of the responders learned about health damages of smoking during medical school classes, 51.4% reported having experimented with at least one of these tobacco products. Most responders who reported feeling the presence of God/the Holy Spirit in their lives were never experimenters of water pipes (59.2%) or e-cigarettes (55.3%). Conclusions: There is a high prevalence of experimentation with tobacco products among medical students whose siblings or friends smoke, despite their knowledge about smoking harms.

RESUMO Objetivo: Avaliar a prevalência de experimentação e uso atual de narguilé e cigarros eletrônicos e os fatores associados entre estudantes de medicina. Métodos: Estudo transversal multicêntrico com uma amostra de conveniência de estudantes de faculdades de medicina da maioria das regiões geográficas brasileiras. Informações sobre experimentação e uso atual de cigarros convencionais, narguilé e cigarros eletrônicos; crenças e atitudes em relação aos produtos do tabaco; religiosidade; e dados demográficos foram coletados por meio de um questionário on-line estruturado. Utilizou-se estatística descritiva e regressão logística para analisar a associação desses fatores. Resultados: Nossa amostra foi composta por 700 indivíduos de quatro regiões brasileiras. As prevalências de experimentação e uso atual de cigarros, narguilé e cigarros eletrônicos foram, respectivamente, de 39,1% e 7,9%; 42,6% e 11,4%; e 13,1% e 2,3%. A experimentação de narguilé foi maior entre aqueles que tinham irmãos (OR ajustada = 2,64; IC95%: 1,24-5,61) ou amigos (OR ajustada = 2,33; IC95%: 1,63-3,31) fumantes. O mesmo ocorreu em relação à experimentação de cigarros eletrônicos: irmãos (OR ajustada = 2,76; IC95%: 1,17-6,50) e amigos (OR ajustada = 2,47; IC95%: 1,45-4,22). Curiosidade e aroma/sabor foram os principais motivos para o uso de narguilé e a experimentação de cigarros eletrônicos. Embora 93% dos respondentes tenham aprendido sobre os danos do tabagismo à saúde nas aulas da faculdade de medicina, 51,4% relataram já ter experimentado pelo menos um desses produtos do tabaco. A maioria dos respondentes que relataram sentir a presença de Deus/Espírito Santo em suas vidas nunca experimentou narguilé (59,2%) ou cigarros eletrônicos (55,3%). Conclusões: Há uma alta prevalência de experimentação de produtos do tabaco entre estudantes de medicina cujos irmãos ou amigos fumam, apesar de terem conhecimento sobre os malefícios do tabagismo.

Use of electronic cigarettes and hookah in Brazil: a new and emerging landscape. The Covitel study, 2022 / Uso de cigarro eletrônico e narguilé no Brasil: um cenário novo e emergente. O estudo Covitel, 2022

ABSTRACT Objective: To estimate the prevalence of current commercial cigarette smoking, as well as those of e-cigarette and hookah experimentation and current use among adults (≥ 18 years of age) in Brazil. Methods: This study was based on a countrywide cross-sectional telephone-based survey conducted in 2022. The sample was designed to be representative of the five macroregions in Brazil and included 1,800 individuals from each of the regions. Telephone numbers, using a random digit dialing procedure, were proportionally selected for each direct distance dialing code in each region and then electronically validated (i.e., 900 cell and 900 landline phone numbers per region). Information on current commercial cigarette smoking (regardless of frequency/amount), as well as lifetime history of or current e-cigarette and hookah use (regardless of amount), were collected. Results: The prevalence of lifetime history of e-cigarette and hookah use was identical (7.3%; 95% CI: 6.0-8.9), whereas the prevalence of current commercial cigarette smoking was 12.2% (95% CI: 10.4-14.1). Young adults (18-24 years) had the highest prevalence of e-cigarette experimentation (19.7%; 95% CI: 15.1-17.0) and hookah experimentation (17%; 95% CI: 12.2-23.2). E-cigarette and hookah use was more common in the Central-West region and among those with a high level of education, whereas current commercial cigarette smoking was more common among those with a lower level of education. Individuals who used the three forms of nicotine delivery corresponded to 1.5% of the sample (nearly 2 million individuals based on the estimated size of the Brazilian adult population). Conclusions: Surveillance is essential for the monitoring and prevention of these new forms of nicotine consumption.

RESUMO Objetivo: Estimar a prevalência do consumo atual de cigarros industrializados, bem como da experimentação e uso atual de cigarro eletrônico e narguilé entre adultos (≥ 18 anos) no Brasil. Métodos: Este estudo baseou-se em uma inquérito telefônico nacional realizada em 2022. A amostra foi projetada para ser representativa das cinco macrorregiões do Brasil e foi composta por 1.800 indivíduos de cada uma das regiões. Por meio de um procedimento de discagem aleatória, os números de telefone foram selecionados proporcionalmente para cada código de discagem direta à distância em cada região e, em seguida, validados eletronicamente (isto é, 900 telefones celulares e 900 telefones fixos por região). Foram coletadas informações sobre o consumo atual de cigarros industrializados (independentemente da frequência/quantidade), bem como sobre a história de uso ou uso atual de cigarro eletrônico e narguilé (independentemente da quantidade). Resultados: As prevalências de história de uso de cigarro eletrônico e narguilé foram idênticas (7,3%; IC95%: 6,0-8,9), ao passo que a prevalência de consumo atual de cigarros industrializados foi de 12,2% (IC95%: 10,4-14,1). Adultos jovens (18-24 anos) apresentaram as maiores prevalências de experimentação de cigarro eletrônico (19,7%; IC95%: 15,1-17,0) e de narguilé (17%; IC95%: 12,2-23,2). O uso de cigarro eletrônico e narguilé foi mais comum na região Centro-Oeste e entre aqueles com maior grau de escolaridade, ao passo que o consumo atual de cigarros industrializados foi mais comum entre aqueles com menor grau de escolaridade. Os indivíduos que usavam as três formas de liberação de nicotina corresponderam a 1,5% da amostra (quase 2 milhões de indivíduos com base na estimativa do tamanho da população adulta brasileira). Conclusões: A vigilância é essencial para o monitoramento e prevenção dessas novas formas de consumo de nicotina.

Ocular surface assessment and morphological alterations in meibomian glands with non-contact meibography in electronic cigarette smokers / Avaliação da superfície ocular e das alterações morfológicas nas glândulas meibomianas através de meibografia sem contato em usuários de cigarros eletrônicos

ABSTRACT Purpose: The study aimed to evaluate the ocular surface and meibomian gland morphology in electronic cigarette (e-cigarette) smokers. Methods: The upper and lower eyelids of 25 male e-cigarette smokers and 25 healthy male non-smoker patients were evaluated using Sirius meibography. Meibomian glands loss was automatically calculated using Phoenix meibography imaging software module, with the result obtained as percentage loss. Ocular Surface Disease Index (OSDI) questionnaire, tear breakup time test, and Schirmer II test were administered and performed in all cases. Results: The mean e-cigarette smoking duration was 4.9 ± 0.9 (range, 3.4-7) years. While the mean Schirmer II test value was 9.16 ± 2.09 mm in e-cigarette group, it was 11.20 ± 2.14 mm in control group (p=0.003). Mean tear breakup time was 6.96 ± 2.31 seconds in e-cigarette group and 9.84 ± 2.13 seconds in control group (p=0.002). The mean OSDI value was 28.60 ± 6.54 and 15.16 ± 7.23 in e-cigarette and control groups, respectively (p<0.001). In Sirius meibography, the average loss for the upper eyelid was 23.08% ± 6.55% in e-cigarette group and 17.60% ± 4.94% in control group (p=0.002), and the average loss for the lower eyelid was 27.84% ± 5.98% and 18.44% ± 5.91%, respectively (p<0.001). Additionally, a significant positive correlation was identified between the loss rates for both upper and lower eyelid meibography with e-cigarette smoking duration (r=0.348, p<0.013 and r=0.550, p<0.001, respectively). Conclusion: Long-term e-cigarette smoking causes damage to the meibomian glands; therefore, meibomian gland damage should be considered in ocular surface disorders due to e-ci­garette smoking.

RESUMO Objetivo: Avaliar a superfície ocular e a morfologia da glândula meibomiana em usuários de cigarros eletrônicos. Métodos: Foram avaliadas através de meibografia Sirius as pálpebras superiores e inferiores de 25 usuários de cigarros eletrônicos do sexo masculino e 25 pacientes não usuários saudáveis, também do sexo masculino. A perda nas glândulas meibomianas foi calculada automaticamente com o módulo de software de imagem de meibografia Phoenix. O resultado foi obtido como perda percentual. O questionário Ocular Surface Disease Index (OSDI), o teste do tempo de ruptura lacrimal e o teste de Schirmer II foram administrados em todos os casos. Resultados: A duração média do uso de cigarros eletrônicos foi de 4,9 ± 0,9 anos (intervalo de 3,4-7 anos). O valor médio do teste de Schirmer II foi de 9,16 ± 2,09 mm no grupo de usuários de cigarros eletrônicos e de 11,20 ± 2,14 mm no grupo controle (p=0,003). O valor médio do teste do tempo de ruptura lacrimal foi de 6,96 ± 2,31 segundos no grupo de usuários de cigarros eletrônicos e 9,84 ± 2,13 segundos no grupo controle (p=0,002). O valor médio do Ocular Surface Disease Index foi de 28,60 ± 6,54 e 15,16 ± 7,23 para os grupos de usuários de cigarros eletrônicos e controle, respectivamente (p<0,001). Na meibografia de Sirius, a perda média para a pálpebra superior foi de 23,08 ± 6,55% para o grupo de usuários de cigarros eletrônicos e 17,60 ± 4,94% para o grupo controle (p=0,002), e a perda média para a pálpebra inferior foi de 27,84 ± 5,98% e 18,44 ± 5,91%, respectivamente (p<0,001). Além disso, foi observada uma correlação positiva significativa entre a taxa de perda na meibografia palpebral superior e inferior com a duração do tabagismo eletrônico, respectivamente de (r=0,348, p<0,013) e (r=0,550, p<0,001). Conclusão: O uso prolongado de cigarros eletrônicos causa danos às glândulas meibomianas. Portanto, esses danos devem ser considerados em distúrbios da superfície ocular devidos ao uso desses dispositivos.

Impacto do uso de produtos de tabaco aquecido (HTP) na qualidade do ar em ambientes fechados / Impact of the use of heated tobacco products (HTP) on indoor air quality

Resumo Introdução: Os produtos de tabaco aquecido (HTP) têm ganhado popularidade nos últimos anos. No entanto, tem-se questionado sobre os danos que provocam na saúde, em especial aos impactos decorrentes da exposição a suas emissões. O objetivo deste estudo é avaliar o impacto do uso de HTPs em ambientes internos/fechados na qualidade do ar e/ou na saúde das pessoas expostas passivamente, por meio de uma revisão sistemática de estudos originais. Métodos: Realizou-se busca bibliográfica nas bases de dados Medical Literature Analysis and Retrieval Sistem (MEDLINE), Excerpta Medica Database (EMBASE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e SCOPUS. As etapas de seleção, extração dos dados e avaliação do risco de viés dos estudos foi realizada em dupla, de forma independente, e as divergências foram resolvidas por consenso. Resultados: Foram selecionados 21 estudos, incluídos nesta revisão. Os resultados indicam que os produtos de tabaco aquecido são fonte de poluição ambiental decorrente da emissão de material particulado. Conclusão: Os produtos de tabaco aquecido produzem emissões que podem expor as pessoas às substâncias tóxicas emitidas no ambiente fechado, assim como outros produtos de tabaco.

Abstract Introduction: Heated tobacco products (HTP) have gained popularity in recent years. However, questions have been raised about the damage they cause to health, especially the impacts resulting from exposure to their emissions. This study aims to evaluate the impact of the use of HTPs indoors on air quality and/or the health of passively exposed people, through a systematic review of original studies. Methods: A bibliographic search was carried out in the Medical Literature Analysis and Retrieval System (MEDLINE), Excerpta Medica Database (EMBASE), Latin American and Caribbean Health Sciences (LILACS) and SCOPUS databases. Results: 21 studies were selected and included in this review. The results indicate that heated tobacco products are a source of environmental pollution due to the emission of particulate matter. The stages of selection, data extraction and risk of bias assessment of the studies were performed in pairs, independently, and disagreements were resolved by consensus. Conclusion: Heated tobacco products produce emissions that can expose people to toxic substances emitted indoors, just like other tobacco products.

Efectos de la exposición pasiva al aerosol de los cigarrillos electrónicos: una revisión de tema / Effects of passive exposure to aerosol from electronic cigarettes: a review

Resumen Los cigarrillos electrónicos sustituyeron el tabaco del cigarrillo convencional por un e-liquid compuesto por varios compuestos orgánicos; estos entraron al mercado sin mayores pruebas toxicológicas preclínicas o ensayos de seguridad a nivel mundial, generando un gran número de personas expuestas al aerosol de segunda mano, en quienes los posibles riesgos aún no han sido dilucidados. El objetivo de esta revisión es identificar los riesgos para la salud de personas expuestas al aerosol de segunda mano de cigarrillos electrónicos. La búsqueda bibliográfica realizó una revisión en las bases de datos PubMed, Scielo y EBSCO, incluyendo estudios realizados en humanos, animales e in vitro. Los principales hallazgos fueron exacerbaciones de asma, enfermedad pulmonar obstructiva crónica, efectos proinflamatorios, estrés oxidativo y ansiedad. La evidencia encontró efectos adversos en personas expuestas al aerosol de segunda mano del cigarrillo electrónico; se destacan exacerbaciones de asma, neumonitis por hipersensibilidad, inflamación y estrés oxidativo.

Abstract Electronic cigarettes replaced the tobacco leaf in conventional cigarettes with an e-liquid composed of multiple organic compounds; these entered the market without major preclinical toxicological tests or safety trials worldwide. Generating a large number of people exposed to second-hand aerosol, to whom the possible risks have not yet been elucidated. The objective of this review was to identify the health risks of people exposed to second-hand aerosol from electronic cigarettes. The review was carried out using PubMed, Scielo and EBSCO databases, including studies carried out in humans, animals and invitro. The main findings were exacerbations of asthma and chronic obstructive pulmonary disease, pro-inflammatory effects, oxidative stress and anxiety. Evidence found adverse effects in people exposed to second-hand aerosol from electronic cigarettes; highlighting exacerbations of asthma, hypersensitivity pneumonitis, inflammation and oxidative stress.

Electronic Cigarettes, Oral Health, and COVID-19: What You Need to Know

ABSTRACT: Known as "vaping devices", electronic cigarettes (e-cigarettes) have been consumed more and more on a global scale, in addition to being considered another factor in the transmission of COVID-19. Electronic cigarettes use chemicals in liquid form, which are incorporated, heated and vaporized. Such solutions may or may not contain nicotine. For this reason, many users of conventional cigarettes rely on the idea of stopping their addiction by switching to electronic cigarettes, with the justification of reduced harm. Despite a scientific knowledge still in formation, unable to remedy all the consequences that these cigarettes cause on the individual's health, as well as their effects on the mouth, the purpose of this article is to discuss the main results that scientific studies have found on this topic and propose an awareness of the population about its harmful effects on health and transmission of COVID-19 by sharing among users.

RESUMEN: Conocidos como "dispositivos de vapeo", los cigarrillos electrónicos (e-cigarettes) se han consumido cada vez más a escala mundial, además de ser considerados un factor adicional en la transmisión del COVID-19. Los cigarrillos electrónicos utilizan productos químicos en forma líquida, que se incorporan, calientan y vaporizan. Tales soluciones pueden o no, contener nicotina. Por esta razón, muchos usuarios de cigarrillos convencionales confían en la idea de dejar su adicción pasándose a los cigarrillos electrónicos, con la justificación de la reducción del daño. A pesar de un conocimiento científico aún en formación es incapaz de remediar todas las consecuencias que estos cigarrillos provocan en la salud del individuo, así como sus efectos en la cavidad oral. El propósito de este artículo fue discutir los principales resultados que los estudios científicos han encontrado sobre este tema y proponer una concientización de la población sobre los efectos nocivos en la salud y transmisión del COVID-19 mediante el intercambio entre usuarios.

Diseño y caracterización de un sistema de entrega de fármacos autoemulsificable (SEDDS) de estradiol por diagramas de fases pseudoternarios y pruebas fisicoquímicas

Introducción: el estradiol es una hormona esteroide sexual femenina usada ampliamente como terapia hormonal que presenta una baja biodisponibilidad, debido a su baja solubilidad acuosa y a su alta hidrofobicidad, perteneciendo a la clase II del sistema de clasificación de biofarmacéutica. Objetivos: diseñar y caracterizar un sistema de entrega de fármacos autoemulsificable (SEDDS) para el fármaco estradiol por pruebas fisicoquímicas con el fin de obtener la relación óptima que permitiera mejorar su solubilidad acuosa, velocidad de disolución y potencialmente su biodisponibilidad. Método: estudios de solubilidad en diferentes solventes, diagramas de fases pseudoternarios constituidos por aceites, tensioactivos, cotensioactivos y agua permitieron reconocer las diferentes regiones de formación de SEDDS e identificar los porcentajes de excipientes que conducen a la formación de soluciones isotrópicas; las formulaciones resultantes fueron caracterizadas en tiempo de autoemulsificación, robustez a la dilución, punto de nube y perfil de disolución en capsula dura. Resultados: las formulaciones que contenían Capmul MCM®, Kolliphor® RH40 y Transcutol®, tuvieron un tiempo de autoemulsificación de aproximadamente 1 min; fueron estables en tres distintos pH (1,2; 4,5 y 7,2), en diferentes volúmenes de dilución, exhibiendo una apariencia transparente, ligeramente azulada, sin precipitados, o separación de fases, puntos de nube mayores en comparación de las formulaciones que contenían Gelucire® 44/14. Conclusiones: las estrategias de caracterización empleadas en el desarrollo de esta investigación demostraron ser eficientes para la selección adecuada de excipientes y su proporción óptima para el diseño eficaz de un sistema de entrega de fármaco autoemulsificable (SEDDS).

SUMMARY Introduction: Estradiol is a female sex steroid hormone widely used as hormonal therapy that has low bioavailability, due to its low aqueous solubility and high hydro-phobicity, belonging to class II of the Biopharmaceutical Classification System. Aim: To design and characterize a self-emulsifying drug delivery system (SEDDS) for the drug estradiol by physicochemical tests to obtain the most optimal ratio that would improve its aqueous solubility, dissolution rate, and potentially its bioavailability. Method: Solubility studies in different solvents; pseudo ternary phase diagrams made up of oils, surfactants, co-surfactants, and water, allowed to recognize the different regions of SEDDS formation and identify the percentages of excipients that lead to the formation of isotropic solutions; The resulting formulations were characterized in autoemulsification time, robustness to dilution, cloud point and dissolution profile in a hard capsule. Results: The formulations containing Capmul MCM®, Kolliphor® RH40, and Transcutol®, had an autoemulsification time of approximately 1 minute; were stable at three different pHs (1.2, 4.5 and 7.2), at different dilution volumes, exhibiting a transparent, slightly bluish appearance, without precipitates, or phase separation, higher cloud points compared to the formulations containing Gelucire® 44/14. Conclusions: The characterization strategies used in the development of this research proved to be efficient for the adequate selection of excipients and their optimal ratio for the effective design of a self-emulsifying drug delivery system (SEDDS).

Introdução: o estradiol é um hormônio esteroide sexual feminino amplamente utilizado como terapia hormonal que apresenta baixa biodisponibilidade devido à sua baixa solubilidade aquosa e alta hidrofobicidade, pertencente à classe II do sistema de classificação biofarmacêutica. Objetivos: projetar e caracterizar um sistema de liberação de drogas autoemulsificante (SEDDS) para o fármaco estradiol por meio de testes físico-químicos a fim de obter a proporção ideal que melhore sua solubilidade aquosa, taxa de dissolução e potencialmente sua biodisponibilidade. Método: estudos de solubilidade em diferentes solventes, diagramas de fases pseudoternários compostos por óleos, tensoativos, cotensoativos e água permitiram reconhecer as diferentes regiões de formação de SEDDS e identificar as porcentagens de excipientes que levam à formação de soluções isotrópicas; as formulações resultantes foram caracterizadas quanto ao tempo de autoemulsificação, robustez à diluição, ponto de turvação e perfil de dissolução da cápsula dura. Resultados: as formulações contendo Capmul MCM®, Kolliphor® RH40 e Transcutol®, tiveram um tempo de autoemulsificação de aproximadamente 1 min; foram estáveis em três diferentes pH's (1,2; 4,5 e 7,2), em diferentes volumes de diluição, apresentando aspecto transparente, levemente azulado, sem precipitados ou separação de fases, pontos de turvação mais elevados em relação às formulações contendo Gelucire® 44/14. Conclusões: as estratégias de caracterização utilizadas no desenvolvimento desta pesquisa mostraram-se eficientes para a seleção adequada de excipientes e sua proporção ideal para o desenho eficaz de um sistema de liberação de fármacos autoemulsificante (SEDDS).