Persistent gender disparity in leading dental publications across four decades: An observational study.

OBJECTIVE: This observational study assessed the differences in the gender of the first and last authors in the most cited dental articles over the last four decades. STUDY DESIGN AND SETTING: Articles were obtained through an electronic search of the most cited articles in dentistry by decade (total n = 400 articles). The 100 most cited studies in each decade (1980 - 1989, 1990 - 1999, 2000 - 2009, and 2010 - 2019), with any study design, with results in dentistry were eligible. The gender of the first and last authors was determined using the Genderize database. Comparative evaluation of gender distribution in general and across the four decades was performed with the Chi-Square test, and the contribution of variables on the citation rate of articles was performed using Linear Regression. RESULTS: There were statistical differences between the gender distributions, with a predominance of men in the first (83.8%) and the last (86.8%) positions (p<0.001). Over the decades, there was a tendency for an increase in the proportion of women as the last author (p = 0.002; Chi-Square Trend Test). However, no statistically significant differences were observed between the genders for the first author in the last four decades (p = 0.163; Chi-Square Trend Test), with an increase of women from 6% to 22% across the last four decades. CONCLUSION: The findings indicate that men lead a large percentage of the most cited articles in dentistry and that this trend does not show substantial modifications over the last years. Nonetheless, for the position of last authorship, an increase in women's representativity was observed over the last decades.

The impact of gender on citation rates: An observational study on the most cited dental articles.

OBJECTIVE: This cross-sectional study aims to determine whether the gender of the authors plays a role in the position of authorship within the 100 most cited articles in dentistry. METHODS: An electronic search was performed in October 2022 in the SCOPUS database, considering filters by 'subject area' [dentistry], 'document type' [article], and 'source type' [journal]. The search was performed without restriction on the study design, publication yearor language. Information regarding each article was then extracted. The gender of the first and last author was determined by associating their first names with the probability of the name being male or female, using the Genderize database. Comparative evaluation of gender distribution was performed with the Chi-Square test. RESULTS: Articles ranged from 5214 to 579 citations. Included studies were published between 1964 and 2019, with the majority being from journals with the highest impact factors in the field. There were statistical significance differences between the gender distribution of the first and last authors, with a predominance of man in both authorships positions (all p<0.00). Only 15% and 12.6% the most cited papers in dental research presented a woman as first and last authors, respectively. CONCLUSION: In conclusion, female authors are not as regarded as male authors in prestigious authorship positions in the most cited dental publications, and gender bias can still be considered prominent in the dental research community. CLINICAL RELEVANCE: The findings of the present study indicate that the gender imbalance in citation practices, reported in several areas, also occurs in the field of Dentistry. It is essential that more discussions be raised about gender disparities and about the female presence in the scientific community.

Epidemiological characteristics and prevalence rates of research reproducibility across disciplines: A scoping review of articles published in 2018-2019.

Background: Reproducibility is a central tenant of research. We aimed to synthesize the literature on reproducibility and describe its epidemiological characteristics, including how reproducibility is defined and assessed. We also aimed to determine and compare estimates for reproducibility across different fields. Methods: We conducted a scoping review to identify English language replication studies published between 2018 and 2019 in economics, education, psychology, health sciences, and biomedicine. We searched Medline, Embase, PsycINFO, Cumulative Index of Nursing and Allied Health Literature - CINAHL, Education Source via EBSCOHost, ERIC, EconPapers, International Bibliography of the Social Sciences (IBSS), and EconLit. Documents retrieved were screened in duplicate against our inclusion criteria. We extracted year of publication, number of authors, country of affiliation of the corresponding author, and whether the study was funded. For the individual replication studies, we recorded whether a registered protocol for the replication study was used, whether there was contact between the reproducing team and the original authors, what study design was used, and what the primary outcome was. Finally, we recorded how reproducibilty was defined by the authors, and whether the assessed study(ies) successfully reproduced based on this definition. Extraction was done by a single reviewer and quality controlled by a second reviewer. Results: Our search identified 11,224 unique documents, of which 47 were included in this review. Most studies were related to either psychology (48.6%) or health sciences (23.7%). Among these 47 documents, 36 described a single reproducibility study while the remaining 11 reported at least two reproducibility studies in the same paper. Less than the half of the studies referred to a registered protocol. There was variability in the definitions of reproduciblity success. In total, across the 47 documents 177 studies were reported. Based on the definition used by the author of each study, 95 of 177 (53.7%) studies reproduced. Conclusions: This study gives an overview of research across five disciplines that explicitly set out to reproduce previous research. Such reproducibility studies are extremely scarce, the definition of a successfully reproduced study is ambiguous, and the reproducibility rate is overall modest. Funding: No external funding was received for this work.

Impact of COVID-19 on gender gap in dental publications: a retrospective cohort with three Brazilian journals.

This was a retrospective cohort study to investigate the impact of COVID-19 pandemic on the gender gap in articles submitted to three international dental journals based in Brazil. All submissions performed to Brazilian Dental Journal, Brazilian Oral Research, and Journal of Applied Oral Science before (2019) and during the pandemic (2020) were assessed. Gender of the first, last, and corresponding authors were collected. Other variables collected were journal, continent studied by authors and stage of their careers (classified according to authors' highest degree), and final decision reached in the article. Absolute and relative frequencies with 95% confidence intervals, Pearson's Chi-square tests, and Fisher's Exact test were used (α = 0.05). In total, 4,726 unique submissions were analyzed. A higher proportion of early-career authors was observed during the pandemic (44.8% to 49.3%, p = 0.021). Most articles were rejected but without association with gender. Increased proportion of male first authors from before to during the pandemic was observed (39% to 42.1%, p = 0.034). Drop in the proportion of articles with women as first authors was observed for researchers in their early- (65.9% to 58.8%, p = 0.02) and mid-career stages (63% to 55.8%, p = 0.014). Reduction in women as first authors was observed during the pandemic in South and Central Americas (66.7% to 61.5%, p = 0.010), and when the last author was a female, or the corresponding author was a male. In conclusion, a disproportionate impact on female dental researchers in submitting articles in the period from before to during the pandemic was observed when considering first authorship, suggesting that the COVID-19 may have increased the gender inequality in dental science.

Vitamin D Supplementation for Benign Paroxysmal Positional Vertigo: A Systematic Review.

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is commonly attributed to displaced otoconia. These have been shown to have biomineralization close to that of bone, and vitamin D deficiency has been associated with BPPV. We aim to systematically review the available literature on vitamin D supplementation and BPPV intensity and recurrence in adults. DATABASES REVIEWED: PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Current Controlled Trials, and ClinicalTrials.gov. METHODS: We systematically reviewed the available literature from 1947 to April 2020. The study protocol was registered in the PROSPERO database (trial registration: CRD42020183195). RESULTS: A total of 179 abstracts were identified and screened by two independent reviewers. Based on inclusion and exclusion criteria, six studies were selected and subjected to a quality assessment. In one randomized clinical trial (RCT), vitamin D supplementation was found to reduce annual recurrence rate of vertigo in patient with BPPV and subnormal serum vitamin D levels compared with placebo (odds ratio, 0.69; 95% confidence interval, 0.54-0.90). Non-RCTs demonstrated the possibility of a null effect in the random effects model (odds ratio, 0.08; 95% confidence interval, 0.00-1.56). The RCT considered as low risk of bias. All of the nonrandomized studies were assessed as serious risk of bias. CONCLUSIONS: The intervention studies identified consistently demonstrated a decrease in BPPV recurrence with supplementation of vitamin D in patients with subnormal vitamin D levels. Although there is a paucity of high-quality studies, the present literature does highlight a role for optimization of vitamin D levels in patients with BPPV.

Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis.

Since clinical approval of the first liposomal formulation encapsulating a chemotherapeutic agent, nanoscale delivery systems have been a rapidly developing science [...].

Combining Nanocarrier-Assisted Delivery of Molecules and Radiotherapy.

Cancer is responsible for a significant proportion of death all over the world. Therefore, strategies to improve its treatment are highly desired. The use of nanocarriers to deliver anticancer treatments has been extensively investigated and improved since the approval of the first liposomal formulation for cancer treatment in 1995. Radiotherapy (RT) is present in the disease management strategy of around 50% of cancer patients. In the present review, we bring the state-of-the-art information on the combination of nanocarrier-assisted delivery of molecules and RT. We start with formulations designed to encapsulate single or multiple molecules that, once delivered to the tumor site, act directly on the cells to improve the effects of RT. Then, we describe formulations designed to modulate the tumor microenvironment by delivering oxygen or to boost the abscopal effect. Finally, we present how RT can be employed to trigger molecule delivery from nanocarriers or to modulate the EPR effect.

Open science failed to penetrate academic hiring practices: a cross-sectional study.

BACKGROUND AND OBJECTIVE: To evaluate the current hiring practices of academic institutions around the world, with regard to the mention of advertisements for Open Science (OS) in research based, faculty, and postdoctoral positions. STUDY DESIGN: Cross-sectional study, using 189 global institutions from the Center for Science and Technology Leiden ranking of world universities of 2017, including the U15 Group (Canadian Research-Intensive Universities), and five self-selected supplementary institutions. METHODS: The main outcome measure for our study is the level of OS in job advertisements, assessed using the Modified Open Science Modular Scheme. RESULTS: After assessing 305 job advertisements for academic positions in 91 institutions, only 2 (0.6%) had any explicit mention of OS in their job advertisements on the Modified Open Science Modular Scheme. The sample assessed the level of open science for 39.0% Associate and/or Assistant professor positions, 30.8% Researcher and/or Postdoctoral fellow positions, and 18.7% of Tenured positions. The remaining 11.5% were for positions such as lectureship, research associate, chair, dean, director and other. CONCLUSION: This study emphasizes the need for increased recognition of OS as a characteristic in research-active job advertisements. As evident in the alarmingly low percentage of job advertisements that mentioned OS (0.6%), the movement towards enhanced OS profiles across academic institutions is highly encouraged. This can be achieved through increased recognition of OS in research job advertisements and demonstrating the means in which institutions promote OS such as, encouraging preprints, publishing in open access journals, and the importance of data sharing.

Impact of COVID-19 on gender gap in dental publications: a retrospective cohort with three Brazilian journals

Abstract This was a retrospective cohort study to investigate the impact of COVID-19 pandemic on the gender gap in articles submitted to three international dental journals based in Brazil. All submissions performed to Brazilian Dental Journal, Brazilian Oral Research, and Journal of Applied Oral Science before (2019) and during the pandemic (2020) were assessed. Gender of the first, last, and corresponding authors were collected. Other variables collected were journal, continent studied by authors and stage of their careers (classified according to authors' highest degree), and final decision reached in the article. Absolute and relative frequencies with 95% confidence intervals, Pearson's Chi-square tests, and Fisher's Exact test were used (α = 0.05). In total, 4,726 unique submissions were analyzed. A higher proportion of early-career authors was observed during the pandemic (44.8% to 49.3%, p = 0.021). Most articles were rejected but without association with gender. Increased proportion of male first authors from before to during the pandemic was observed (39% to 42.1%, p = 0.034). Drop in the proportion of articles with women as first authors was observed for researchers in their early- (65.9% to 58.8%, p = 0.02) and mid-career stages (63% to 55.8%, p = 0.014). Reduction in women as first authors was observed during the pandemic in South and Central Americas (66.7% to 61.5%, p = 0.010), and when the last author was a female, or the corresponding author was a male. In conclusion, a disproportionate impact on female dental researchers in submitting articles in the period from before to during the pandemic was observed when considering first authorship, suggesting that the COVID-19 may have increased the gender inequality in dental science.

The impact of gender on researchers' assessment: A randomized controlled trial.

OBJECTIVES: This randomized controlled trial aimed to test whether women or men would be preferred with identical curriculum vitae (CV); and the impact of the career stage in the evaluators' choice. STUDY DESIGN AND SETTING: A simulated post-doctoral process was carried forward to be assessed for judgment. Level 1 and 2 Brazilian fellow researchers in the field of Dentistry were invited to act as external reviewers in a post-doctoral process and were randomly assigned to receive a CV from a woman or a man. They were required to rate the CV from 0 to 10 in scientific contribution, leadership potential, ability to work in groups, and international experience. RESULTS: For all categories of CVs evaluated, CVs from men received higher scores compared to the CVs from women. Robust variance Poisson regressions demonstrated that men were more likely to receive higher scores in all categories, despite applicants' career stage. For example, CVs from men were nearly three quarters more likely to be seen as having leadership potential than equivalent CVs from women. CONCLUSION: Gender bias is powerfully prevalent in academia in the dentistry field, despite researchers' career stage. Actions like implicit bias training must be urgently implemented to avoid (or at least decrease) that more women are harmed.

Triggered Drug Release From Liposomes: Exploiting the Outer and Inner Tumor Environment.

Since more than 40 years liposomes have being extensively studied for their potential as carriers of anticancer drugs. The basic principle behind their use for cancer treatment consists on the idea that they can take advantage of the leaky vasculature and poor lymphatic drainage present at the tumor tissue, passively accumulating in this region. Aiming to further improve their efficacy, different strategies have been employed such as PEGlation, which enables longer circulation times, or the attachment of ligands to liposomal surface for active targeting of cancer cells. A great challenge for drug delivery to cancer treatment now, is the possibility to trigger release from nanosystems at the tumor site, providing efficacious levels of drug in the tumor. Different strategies have been proposed to exploit the outer and inner tumor environment for triggering drug release from liposomes and are the focus of this review.

The impact of gender on scientific writing: An observational study of grant proposals.

OBJECTIVES: This study aimed to determine whether there are differences in the language used in grant applications submitted to a Southern Brazil Research Support Foundation (FAPERGS) according to the gender, career stage, and the number of publications of applicants. STUDY DESIGN AND SETTING: This observational study also evaluated the relationship between gender, career stage, curriculum, and writing characteristics. Summaries of all research proposals in the biomedical field of FAPERGS during the years of 2013 and 2014 were evaluated according to six language patterns (Positive emotions, Negative emotions, Analytic thinking, Clout, Authenticity, and Emotional tone) defined by the LIWC software. Applicant's gender, career stage, and the number of publications were also collected. RESULTS: Three hundred and forty-four (344) grant proposals met the inclusion criteria and were included in the analysis. No statistical differences were observed in the language pattern used by different gender applicants. In the language used by successful and unsuccessful applicants, we only found a small difference for clout (score 54.5 for not funded and 56.5 for funded grants). However, the principal investigators of successful applications had a significantly higher number of papers published (mean number of papers: 104 versus 58.5). CONCLUSIONS: Gender bias appears to be a more complex problem than just the type of language used; the way society is organized causes several gender biases that may be reflected throughout the women's career.

Desigualdade de gênero e escuta psi de mulheres atendidas na atenção básica / Gender inequality and psychological listening of women attended in primary healthcare / Desigualdad de género y escucha de mujeres que procuran atención primaria

Este estudo tem como objetivo investigar o que psicólogos na atenção básica de Porto Alegre identificam como necessidades em saúde mental das mulheres atendidas, buscando verificar se sua escuta profissional permite estabelecer nexos entre o sofrimento psíquico e a desigualdade de gênero vivenciada pelas usuárias. Em 2017, foi realizado grupo focal com nove psicólogas que atuam em unidades de Saúde da Família, em que foi construída coletivamente uma narrativa segundo o método de Grupo Focal Narrativo. Constituem a narrativa final oito núcleos argumentais: "Sofrimento mascarado"; "Os homens também sofrem com isso"; "Várias gerações de mulheres cuidadoras"; "Aquele desejo de constituir uma família a qualquer custo"; "Por que o homem acha que pode usar uma mulher como se fosse um objeto?"; "Maternidade compulsória"; "Novas formas de exercício da sexualidade"; e "O hospital tomou como uma afronta o empoderamento da mulher". Considera-se que o estudo proporcionou às participantes um espaço de reflexão coletiva sobre si mesmas e suas práticas.(AU)

This study aims to investigate the mental health need of female patient as to psychologists working in primary healthcare services in Porto Alegre - Brazil, verifying whether their psychological listening establishes associations between the psychological suffering and gender inequality experienced by the users. Based on a Narrative Focus Group methodology, a focus group with nine psychologists from Family Health services was conducted in 2017. The final narrative consists of eight argumentative nuclei: "masked suffering," "men also suffer from this," "several generations of female caregivers," "that desire to set up a family at any cost," "why do men think they can use a woman as if she were an object?," "compulsory maternity", "new ways of exercising sexuality," and "the hospital took woman's empowerment as an affront." This study provided participants a space for collectively reflecting on themselves and on their practices.(AU)

Este estudio tiene como objetivo conocer lo que los psicólogos en la atención primaria de Porto Alegre (Brasil) identifican como necesidades en salud mental de las mujeres que procuran atención, con el fin de verificar si su escucha profesional posibilita establecer nexos entre el sufrimiento psíquico y la desigualdad de género vivida por las usuarias. En el 2017, se realizó un grupo focal con nueve psicólogas que actúan en Unidades de Salud Familiar y se construyó colectivamente una narrativa conforme al método de grupo focal narrativo. Ocho núcleos argumentales constituyeron la narrativa final: "Sufrimiento enmascarado"; "Los hombres también sufren con eso"; "Varias generaciones de mujeres cuidadoras"; "La intención de constituir una familia sin importar el costo"; "¿Por qué el hombre cree que puede usar a una mujer como un objeto?"; "Maternidad obligatoria"; "Nuevas formas de ejercicio de la sexualidad"; y "El hospital cree ser una afrenta el empoderamiento femenino". Se considera que el grupo focal proporcionó a las participantes un espacio de reflexión colectiva acerca de sí mismas y de sus prácticas.(AU)

The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer.

Today, pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a five-year overall survival rate of less than 7%. Only 15-20% of patients are eligible for curative intent surgery at the time of diagnosis. Therefore, neoadjuvant treatment regimens have been introduced in order to downsize the tumor by chemotherapy and radiotherapy. To further increase the efficacy of radiotherapy, novel molecular biomarkers are urgently needed to define the subgroup of pancreatic cancer patients who would benefit most from radiotherapy. MicroRNAs (miRNAs) could have the potential to serve as novel predictive and prognostic biomarkers in patients with pancreatic cancer. In the present article, the role of miRNAs as blood biomarkers, which are associated with either radioresistance or radiation-induced changes of miRNAs in pancreatic cancer, is discussed. Furthermore, the manuscript provides own data of miRNAs identified in a pancreatic cancer mouse model as well as radiation-induced miRNA changes in the plasma of tumor-bearing mice.

Transparency in clinical trials: Adding value to paediatric dental research.

BACKGROUND: Even though considered as studies with high methodological power, many RCTs in paediatric dentistry do not have essential quality items in their design, development, and report, making results' reliability questionable, replication challenging to conduct, wasting time, money, and efforts, and even exposing the participants to research for no benefit. AIM: We addressed the main topics related to transparency in clinical research, with an emphasis in paediatric dentistry. DESIGN: We searched for all controlled clinical trials published from January 2019 up to July 2020 in the three paediatric dentistry journals with high journal Impact Factor, indexed on Medline. These papers were assessed for transparency according to Open Science practices and regarding reporting accuracy using some items required by CONSORT. RESULTS: 53.6% of the studies declared registration, 75% had sample size calculation, 98.2% reported randomisation, and from those, 65.4% explained the randomisation method. Besides that, no study shared their data, and 6.8% were published in open access format. CONCLUSIONS: Unfortunately, a large proportion of RCTs in paediatric dental research show a lack of transparency and reproducibility.

Screening tool for restrictive and obstructive ventilatory abnormalities in a population-based survey

Abstract Background: A 6 s spirometry with an inexpensive pocket spirometer efficiently selects individuals for a diagnostic-quality spirometry for airflow limitation, but could also be useful to identify individuals with a restrictive pattern. Objectives: We evaluated an inexpensive simplified spirometer (chronic obstructive pulmonary disease [COPD]-6) as a screening tool to identify spirometric abnormalities. Methods: A population-based survey in Mexico City, with 742 participants performing pre- and post-BD spirometry and a three-maneuver 6 s spirometry (pre-BD) with a COPD-6. We evaluated forced expiratory volume in 1 s (FEV1), FEV6, and FEV1/FEV6 from the COPD-6, crude and expressed as the percentage of predicted (%P), to discriminate post-bronchodilator airflow obstruction (FEV1/forced vital capacity [FVC] <5th percentile) or restriction (FVC or FEV1 <5th percentile with normal FEV1/FVC) through receiver operating characteristics and their area under the curve (AUC). Results: FEV1%P was the best predictor to identify pre- and post-BD ventilatory abnormalities (best cutoff point 87%P, AUC 92% for restrictive pattern, 89% for obstructive pattern, and 91% for any spirometric abnormality). Deriving to clinical spirometry only those with <87%P (26% of the sample) missed only 12% of spirometric abnormalities most of the latter mild. Conclusions: An FEV1 <87%P from a pre-BD 6 s spirometry correctly identified individuals with spirometric ventilatory defects, either obstructive or restrictive.

Combined paclitaxel-doxorubicin liposomal results in positive prognosis with infiltrating lymphocytes in lung metastasis.

Aim: To investigate the effect of liposomes containing the classical cytotoxic drugs paclitaxel and doxorubicin (Lipo-Pacli/Dox), against a metastatic breast cancer model. We also investigated if Lipo-Pacli/Dox was capable of reverting the tolerogenic environment of metastatic lesions. Materials & methods: Immunogenic cell death induction by the Pacli/Dox combination was assessed in vitro. Antitumor activity and in vivo safety of Lipo-Pacli/Dox were evaluated using a 4T1 breast cancer mouse model Results: Lipo-Pacli/Dox, with a size of 189 nm and zeta potential of -5.01 mV, promoted immune system activation and partially controlled the progression of pulmonary metastasis. Conclusion: Lipo-Pacli/Dox was useful to control both primary tumor and lung metastasis in breast cancer (4T1) mice model. Additionally, Lipo-Pacli/Dox acts as an immunological modulator for this metastatic breast cancer model.

Screening Tool for Restrictive and Obstructive Ventilatory Abnormalities in a Population-Based Survey.

BACKGROUND: A 6 s spirometry with an inexpensive pocket spirometer efficiently selects individuals for a diagnostic-quality spirometry for airflow limitation, but could also be useful to identify individuals with a restrictive pattern. OBJECTIVES: We evaluated an inexpensive simplified spirometer (chronic obstructive pulmonary disease [COPD]-6) as a screening tool to identify spirometric abnormalities. METHODS: A population-based survey in Mexico City, with 742 participants performing pre- and post-BD spirometry and a three-maneuver 6 s spirometry (pre-BD) with a COPD-6. We evaluated forced expiratory volume in 1 s (FEV1), FEV6, and FEV1/FEV6 from the COPD-6, crude and expressed as the percentage of predicted (%P), to discriminate post-bronchodilator airflow obstruction (FEV1/forced vital capacity [FVC] < 5th percentile) or restriction (FVC or FEV1 <5th percentile with normal FEV1/FVC) through receiver operating characteristics and their area under the curve (AUC). RESULTS: FEV1%P was the best predictor to identify pre- and post-BD ventilatory abnormalities (best cutoff point 87%P, AUC 92% for restrictive pattern, 89% for obstructive pattern, and 91% for any spirometric abnormality). Deriving to clinical spirometry only those with < 87%P (26% of the sample) missed only 12% of spirometric abnormalities most of the latter mild. CONCLUSIONS: An FEV1 < 87%P from a pre-BD 6 s spirometry correctly identified individuals with spirometric ventilatory defects, either obstructive or restrictive.

Development of Long-Circulating and Fusogenic Liposomes Co-encapsulating Paclitaxel and Doxorubicin in Synergistic Ratio for the Treatment of Breast Cancer.

BACKGROUND: The co-encapsulation of paclitaxel (PTX) and doxorubicin (DXR) in liposomes has the potential to offer pharmacokinetic and pharmacodynamic advantages, providing delivery of both drugs to the tumor at the ratio required for synergism. OBJECTIVE: To prepare and characterize long-circulating and fusogenic liposomes co-encapsulating PTX and DXR in the 1:10 molar ratio (LCFL-PTX/DXR). METHODS: LCFL-PTX/DXR was prepared by the lipid film formation method. The release of PTX and DXR from liposomes was performed using a dialysis method. Studies of cytotoxicity, synergism, and cellular uptake were also carried out. RESULTS: The encapsulation percentage of PTX and DXR was 74.1 ± 1.8 % and 89.6 ± 12.3%, respectively, and the mean diameter of the liposomes was 244.4 ± 28.1 nm. The vesicles remained stable for 30 days after their preparation. The drugs were simultaneously released from vesicles during 36 hours, maintaining the drugs combination in the previously established ratio. Cytotoxicity studies using 4T1 breast cancer cells showed lower inhibitory concentration 50% (IC50) value for LCFL-PTX/DXR treatment (0.27 ± 0.11 µm) compared to the values of free drugs treatment. In addition, the combination index (CI) assessed for treatment with LCFL-PTX/DXR was equal to 0.11 ± 0.04, showing strong synergism between the drugs. Cell uptake studies have confirmed that the molar ratio between PTX and DXR is maintained when the drugs are administered in liposomes. CONCLUSION: It was possible to obtain LCFL-PTX/DXR suitable for intravenous administration, capable of releasing the drugs in a fixed synergistic molar ratio in the tumor region.

Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin.

BACKGROUND: Associating paclitaxel (PTX) to doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Protocols currently available consist in administering both drugs on their maximum tolerated dose, not taking into account the possible differences in efficacy due to their combination ratio. In the present study, the short and long-term cytotoxic effects as well as migratory effects of PTX, DXR, and its combinations at 10:1; 1:1 and 1:10 PTX:DXR molar ratios either free or co-encapsulated in liposomes were evaluated against three human BC cell lines (MDA-MB-231, MCF-7, and SKBR-3). METHOD: The MTT assay was used to screen for synergy or antagonism between PTX and DXR and the combination index value was calculated using the CalcuSyn software. Nuclear morphological alterations were evaluated by staining the cells with Hoescht 33342. The investigation of senescence and clonogenicity of BC cell lines exposed to different treatments was also studied. In addition, the ability of these cells to migrate was assessed. RESULTS: Taken together, the results presented herein allow us to suggest that there is no benefit in enhancing the PTX concentration above that of DXR in the combination for any of the three cell lines tested. CONCLUSION: The developed liposomes co-encapsulating PTX and DXR in different molar ratios retained the biological properties of the mixture of free drugs and are valuable for planning new therapeutic strategies.