Prediabetes remission after bariatric surgery: a 4-years follow-up study.

BACKGROUND: Bariatric surgery leads to weight loss and to cardiometabolic risk improvement. Although prediabetes remission after bariatric surgery is biologically plausible, data on this topic is scarce. We aimed to assess prediabetes remission rate and clinical predictors of remission in a 4 year follow up period. METHODS: Observational longitudinal study including patients with obesity and prediabetes who had undergone bariatric surgery in our centre. Prediabetes was defined as having a baseline glycated haemoglobin (A1c) between 5.7% and 6.4% and absence of anti-diabetic drug treatment. We used logistic regression models to evaluate the association between the predictors and prediabetes remission rate. RESULTS: A total of 669 patients were included, 84% being female. The population had a mean age of 45.4 ± 10.1 years-old, body mass index of 43.8 ± 5.7 kg/m2, and median A1c of 5.9 [5.8, 6.1]%. After bariatric surgery, prediabetes remission rate was 82%, 73%, 66%, and 58%, respectively in the 1st, 2nd, 3rd, and 4th years of follow-up. Gastric sleeve (GS) surgery was associated with higher prediabetes remission rate than Roux-en-Y gastric bypass surgery in the 3rd year of follow-up. Men had a higher remission rate than women, in the 1st and 3nd years of follow-up in the unadjusted analysis. Younger patients presented a higher remission rate comparing to older patients in the 3rd year of follow-up. CONCLUSION: We showed a high prediabetes remission rate after bariatric surgery. The remission rate decreases over the follow-up period, although most of the patients maintain the normoglycemia. Prediabetes remission seems to be more significant in patients who had undergone GS, in male and in younger patients.

COVID-19 Lockdown and Impact on 2-Year Weight Loss in a Bariatric Center.

INTRODUCTION: The COVID-19 pandemic has led to a worldwide lockdown, which affected physical exercise habits, as well as having a detrimental effect on psychological health and follow-up visits of patients submitted to bariatric surgery. The aim of this study was to evaluate the impact of COVID-19 lockdown on the 2-year weight loss of patients submitted to bariatric surgery in our center. METHODS: This was an observational study comparing the weight loss of patients who underwent bariatric surgery from January to March 2020 with a control group submitted to surgery between January and March 2017. Percentage of total weight loss (% TWL) and excess weight loss (% EWL) were assessed 6, 12, and 24 months after surgery. RESULTS: A total number of 203 patients were included in this study, 102 had bariatric surgery during the selected period in 2020 and 101 underwent surgery during the same period in 2017. There was no statistically significant difference in weight loss between the 2017 and 2020 groups which was reported as % TWL (mean 27.08 ± 7.530 vs. 28.03 ± 7.074, 33.87 ± 8.507 vs. 34.07 ± 8.979 and 34.13 ± 9.340 vs. 33.98 ± 9.993; p = 0.371) and % EWL (mean 66.83 ± 23.004 vs. 69.71 ± 17.021, 83.37 ± 24.059 vs. 84.51 ± 21.640 and 83.47 ± 24.130 vs. 84.27 ± 23.651; p = 0.506) at 6, 12, and 24 months post-surgery. CONCLUSION: Despite social limitations imposed by the COVID-19 lockdown, we found no significant difference between weight loss at 2 years postoperatively in the 2020 group when compared with a control group who underwent bariatric surgery in 2017. These results show that the outcomes of bariatric surgery during the COVID-19 lockdown were comparable with those recorded before the pandemic, supporting the efficacy of bariatric procedures' metabolic effects during the first 2 years after surgery, regardless of lifestyle habits.

Klinefelter syndrome: The characterization of the clinical and sociological features of 51 patients / Síndrome de Klinefelter: caracterización de los rasgos clínicos y sociológicos de 51 pacientes

Introduction: Klinefelter syndrome is the most frequently found aneuploidy among male patients. Its clinical presentation is very heterogeneous, and thus poses a challenge for a timely diagnosis. Methods: A retrospective study was carried out with 51 consecutively selected patients diagnosed with Klinefelter Syndrome from Jan/2010 to Dec/2019. The karyotypes were identified using high resolution GTL banding at the Genetics Department. Multiple clinical and sociological parameters were studied by collecting data from the clinical records. Results: 44 (86%) of the 51 patients presented a classical karyotype (47,XXY) and 7 (14%) showed evidence of mosaicism. The mean age at diagnosis was 30.2±14.3 years old. Regarding the level of education (N=44), 26 patients (59.1%) had no secondary education, with 5 (11.4%) patients having concluded university studies. Almost two thirds of the sample revealed learning difficulties (25/38) and some degree of intellectual disability was present in 13.6% (6/44). Half of the patients were either non-qualified workers (19.6%) or workers in industry, construction, and trades (30.4%), which are jobs that characteristically require a low level of education. The proportion of unemployed patients was 6.5%. The main complaints were infertility (54.2%), followed by hypogonadism-related issues (18.7%) and gynecomastia (8.3%). 10 patients (23.8%, N=42) were biological parents. With regards the question of fertility, assisted reproductive techniques were used in 39.6% of the studied subjects (N=48), with a success rate (a take home baby) of 57.9% (11/19), 2 with donor sperm and 9 with the patients’ own gametes. Only 41% of the patients (17/41) were treated with testosterone. (AU)

Introducción: El síndrome de Klinefelter es la aneuploidía más frecuente entre los pacientes varones. Su presentación clínica es muy heterogénea, por lo que supone un reto para su diagnóstico oportuno. Métodos: Se realizó un estudio retrospectivo con 51 pacientes seleccionados consecutivamente con diagnóstico de Síndrome de Klinefelter desde enero de 2010 hasta diciembre de 2019. Los cariotipos se identificaron mediante bandeo GTL de alta resolución en el Departamento de Genética. Se estudiaron múltiples parámetros clínicos y sociológicos mediante la recogida de datos de las historias clínicas. Resultados: De los 51 pacientes, 44 (86%) presentaron un cariotipo clásico (47,XXY) y siete (14%) evidenciaron mosaicismo. La edad media al diagnóstico fue de 30,2 ± 14,3 años. En cuanto al nivel de estudios (n = 44), 26 pacientes (59,1%) no tenían estudios secundarios, y cinco (11,4%) habían concluido estudios universitarios. Casi dos tercios de la muestra revelaban dificultades de aprendizaje (25/38) y algún grado de discapacidad intelectual estaba presente en 13,6% (6/44). La mitad de los pacientes eran trabajadores no cualificados (19,6%) o trabajadores de la industria, la construcción y los oficios (30,4%), que son empleos que característicamente requieren un bajo nivel educativo. La proporción de pacientes en paro era de 6,5%. Las principales quejas eran la infertilidad (54,2%), seguida de problemas relacionados con el hipogonadismo (18,7%) y la ginecomastia (8,3%); 10 pacientes (23,8%, n = 42) eran padres biológicos. En cuanto a la cuestión de la fertilidad, se utilizaron técnicas de reproducción asistida en 39,6% de los sujetos estudiados (n = 48), con una tasa de éxito (un bebé para llevar a casa) de 57,9% (11/19), dos con semen de donante y nueve con gametos propios de los pacientes. Solo 41% de los pacientes (17/41) fueron tratadas con testosterona. (AU)

Klinefelter syndrome: The characterization of the clinical and sociological features of 51 patients.

INTRODUCTION: Klinefelter syndrome is the most frequently found aneuploidy among male patients. Its clinical presentation is very heterogeneous, and thus poses a challenge for a timely diagnosis. METHODS: A retrospective study was carried out with 51 consecutively selected patients diagnosed with Klinefelter Syndrome from Jan/2010 to Dec/2019. The karyotypes were identified using high resolution GTL banding at the Genetics Department. Multiple clinical and sociological parameters were studied by collecting data from the clinical records. RESULTS: 44 (86%) of the 51 patients presented a classical karyotype (47,XXY) and 7 (14%) showed evidence of mosaicism. The mean age at diagnosis was 30.2±14.3 years old. Regarding the level of education (N=44), 26 patients (59.1%) had no secondary education, with 5 (11.4%) patients having concluded university studies. Almost two thirds of the sample revealed learning difficulties (25/38) and some degree of intellectual disability was present in 13.6% (6/44). Half of the patients were either non-qualified workers (19.6%) or workers in industry, construction, and trades (30.4%), which are jobs that characteristically require a low level of education. The proportion of unemployed patients was 6.5%. The main complaints were infertility (54.2%), followed by hypogonadism-related issues (18.7%) and gynecomastia (8.3%). 10 patients (23.8%, N=42) were biological parents. With regards the question of fertility, assisted reproductive techniques were used in 39.6% of the studied subjects (N=48), with a success rate (a take home baby) of 57.9% (11/19), 2 with donor sperm and 9 with the patients' own gametes. Only 41% of the patients (17/41) were treated with testosterone. CONCLUSION: This study identifies the most important clinical and sociological findings of Klinefelter syndrome patients that should be considered when deciding workout and disease management.

Total thyroidectomy in a patient awaiting heart transplant with amiodarone-induced thyrotoxicosis: A case report.

Thyroid function may have a severe impact in cardiac function. Herein, we present the case report of a 53-year-old male patient awaiting heart transplant with amiodarone induced thyrotoxicosis that presented a marked improvement of his cardiac function after total thyroidectomy.

Liraglutide Effectiveness in Type 2 Diabetes: Insights from a Real-World Cohort of Portuguese Patients.

Liraglutide is a long-acting glucagon-like peptide-1 receptor agonist prescribed to diabetic patients for glycaemic control. To understand the impact of liraglutide in the real-world setting, this study analysed its effects in a Portuguese cohort of Type 2 diabetes patients. This was an observational, multicentric, and retrospective study that included 191 liraglutide-treated patients with at least 12 months of treatment. Patients' data were collected and analysed during a 24-month follow-up period. Overall, liraglutide treatment effectively reduced HbA1c levels from 8.3% to around 7.5%, after 6, 12, and 24 months (p < 0.001). In fact, 38.2%, 37.2%, and 44.8% of patients at 6, 12, and 24 months, respectively, experienced an HbA1c reduction of at least 1%. Moreover, a persistent reduction in anthropometric features was also observed, with 44.0%, 47.6%, and 54.4% of patients achieving a weight reduction of at least 3% at 6, 12, and 24 months, respectively. Finally, significant improvements were observed in the HDL-c and LDL-c levels. Our results demonstrate that liraglutide effectively promoted the reduction of HbA1c values during routine clinical practice, which was sustained throughout the study. In addition, there were significant improvements in anthropometric parameters and other cardiovascular risk factors.

Waist-to-Hip Ratio and Inflammatory Parameters Are Associated with Risk of Non-Alcoholic Fatty Liver Disease in Patients with Morbid Obesity.

Non-alcoholic fatty liver disease (NAFLD) is associated with several other metabolic disorders, which are typically pro-inflammatory states. Body fat content is an important marker of metabolic health and abdominal fat is associated with harmful cardiometabolic outcomes. We aimed to evaluate the association between the risk of NAFLD (through Fatty Liver Index (FLI), and BMI, AST/ALT ratio, and presence of diabetes (BARD)), and anthropometric parameters, predictors of metabolic status, in patients with morbid obesity, and to evaluate the association of FLI and BARD scores with pro-inflammatory markers. We have retrospectively studied patients with morbid obesity followed in our center. In total, 2184 participants were included, with an average age of 42.8 ± 10.6 years, 84.5% being females. We report a positive association of FLI with waist circumference (ß = 0.10 [0.09 to 0.11], p < 0.01) and waist-to-hip ratio (ß = 8.68 [6.85 to 10.52, p < 0.01]), even after adjusting for age, sex, body mass index, diabetes, and dyslipidemia (p < 0.01 for both adjusted models). The associations of BARD with anthropometric measures were significant only in the non-adjusted model. There was a positive association between both FLI and BARD and C-reactive protein. Our results point towards a positive association between waist-to-hip ratio and the risk of hepatic steatosis, and between pro-inflammatory markers and both hepatic steatosis and fibrosis.

Statin Therapy Among Bariatric Patients: The Impact on Metabolic Outcomes and Diabetes Status.

INTRODUCTION: Statin therapy is associated with an increased risk of developing diabetes. Among bariatric patients, the influence of this therapy on various metabolic outcomes, such as diabetes status and its remission, is largely unknown. METHODS: This was a retrospective study of 1710 patients who underwent bariatric surgery at our hospital between January/2010 and June/2017. We compared patients with and without statin therapy at baseline, 12 and 24 months after surgery regarding statin use and its impact on several clinical and analytical parameters. Multiple linear regression was performed, adjusting differences for age, sex, surgery type, antidiabetic drugs at baseline, hypertension at baseline, LDL cholesterol ˃ 130 mg/dL, weight variation one year after surgery, and age of obesity onset. RESULTS: The overall prevalence of statin use was 20.2% before, 13.6% 12 months after surgery, and 15.0% 24 months after surgery. There was a larger reduction in fasting glucose and HbA1c at 12 and 24 months after surgery among statin-treated patients, with the opposite trend for weight reduction and BMI. Statin-treated patients with diabetes had lower diabetes remission rates (45.3 vs 68.5%) 12 months after surgery, with the highest reduction in HbA1c (1.3±1.3 vs -1.1±1.2%; p=0.042), fasting glucose (-40.8±48.8 vs -30.9±41.6 mg/dL; p=0.028), and insulin (-21.7±28.2 vs -13.4±14.2 mIU/L; p=0.039). The proportion of new-onset cases of diabetes was equal between statin-treated vs non-treated individuals at 12 months (1.9%) and 24 months (1.0%) after surgery. CONCLUSION: Bariatric surgery seems to lead to diabetes remission more frequently in patients not treated with statins. A larger reduction was observed in fasting glucose and HbA1c among statin-treated patients. Statin did not contribute to an increased proportion of new-onset diabetes after surgery.

Genotoxicity Assessment of Metal-Based Nanocomposites Applied in Drug Delivery.

Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for several applications in the biomedical field, from therapeutics to diagnostics. Green nanocomposites stand for nanoparticles of biocompatible, biodegradable and non-toxic profiles. When using metal nanoparticles for drug delivery, the question of how hazardous these "virus-sized particles" can be is posed, due to their nanometer size range with enhanced reactivity compared to their respective bulk counterparts. These structures exhibit a high risk of being internalized by cells and interacting with the genetic material, with the possibility of inducing DNA damage. The Comet Assay, or Single-Cell Gel Electrophoresis (SCGE), stands out for its capacity to detect DNA strand breaks in eukaryotic cells. It has huge potential in the genotoxicity assessment of nanoparticles and respective cells' interactions. In this review, the Comet assay is described, discussing several examples of its application in the genotoxicity evaluation of nanoparticles commonly administered in a set of routes (oral, skin, inhaled, ocular and parenteral administration). In the nanoparticles boom era, where guidelines for their evaluation are still very limited, it is urgent to ensure their safety, alongside their quality and efficacy. Comet assay or SCGE can be considered an essential tool and a reliable source to achieve a better nanotoxicology assessment of metal nanoparticles used in drug delivery.

Beta Cell Function as a Baseline Predictor of Weight Loss After Bariatric Surgery.

Background: Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain. Aim: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of ß-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery). Results: There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (ß = -1.04 [-1.82 to -0.26], p<0.01; ß = -1.16 [-2.13 to -0.19], p=0.02; ß = -1.29 [-2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery. Conclusion: ß-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.

Secondary Hyperparathyroidism Among Bariatric Patients: Unraveling the Prevalence of an Overlooked Foe.

INTRODUCTION: Bariatric surgery (BS) is the most effective therapeutic approach to obesity. It is associated with great gastrointestinal anatomic changes, predisposing the patients to altered nutrient absorption that impacts phosphocalcium metabolism. This study aimed to clarify the prevalence of secondary hyperparathyroidism (SHPT) and its predictors in patients submitted to BS. METHODS: Retrospective study of 1431 patients who underwent metabolic surgery between January 2010 and June 2017 and who were followed for at least 1 year. We compared the clinical and biochemical characteristics of patients with and without secondary hyperparathyroidism (considering SHPT a PTH ˃ 69 pg/mL). Two different analyses were performed: (1) paired analysis of participants before and 1 year after surgery (N = 441); (2) Cross sectional analysis of participants submitted to bariatric surgery before (N = 441), 1 year after (N = 1431) and 4 years after surgery (N = 333). Multiple logistic regression models were used to evaluate possible predictors of SHPT after BS. RESULTS: The overall prevalence of SHPT was 24.9% before surgery, 11.2% 1 year after surgery and 21.3% 4 years after surgery. Patients submitted to LAGB had the highest prevalence of SHPT 1 year after surgery (19.4%; vs RYGB, 12.8%, vs SG, 5.3%). Four years after surgery, RYGB had the highest prevalence of SHPT (27.0%), followed by LAGB (13.2%) and SG (6.9%). Higher body mass index and age, decreased levels of vitamin D and RYGB seem to be independent predictors of SHPT 1 year after surgery. The only independent predictor of SHPT 4 years after surgery was RYGB. CONCLUSION: The prevalence of SHPT is higher before and 4 years after BS than 1 year after surgery. This fact raises some questions about the efficacy of the implemented follow-up plans of vitamin D supplementation on the long term, mainly among patients submitted to RYGB.

Hyperandrogenism, oligomenorrhea, and erythrocytosis caused by an ovarian Leydig cell tumor: A case report.

Leydig cell tumors are rare ovarian neoplasms. Affected individuals typically present with amenorrhea/oligomenorrhea and rapidly progressive features of virilization. Erythrocytosis can also occur as a result of high testosterone levels.

Natural Ergot Alkaloids in Ocular Pharmacotherapy: Known Molecules for Novel Nanoparticle-Based Delivery Systems.

Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to humans and animals. Their pharmacological profile results from the structural similarity between lysergic acid-derived compounds and noradrenalin, dopamine, and serotonin neurotransmitters. To reduce their toxicological risk, while increasing their bioavailability, improved delivery systems were proposed. This review discusses the safety aspects of using ergot alkaloids in ocular pharmacology and proposes the development of lipid and polymeric nanoparticles for the topical administration of these drugs to enhance their therapeutic efficacy for the treatment of glaucoma.

The Nutraceutical Value of Carnitine and Its Use in Dietary Supplements.

Carnitine can be considered a conditionally essential nutrient for its importance in human physiology. This paper provides an updated picture of the main features of carnitine outlining its interest and possible use. Particular attention has been addressed to its beneficial properties, exploiting carnitine's properties and possible use by considering the main in vitro, in animal, and human studies. Moreover, the main aspects of carnitine-based dietary supplements have been indicated and defined with reference to their possible beneficial health properties.

In Vitro Characterization, Modelling, and Antioxidant Properties of Polyphenon-60 from Green Tea in Eudragit S100-2 Chitosan Microspheres.

Eudragit S100-coated chitosan microspheres (S100Ch) are proposed as a new oral delivery system for green tea polyphenon-60 (PP60). PP60 is a mixture of polyphenolic compounds, known for its active role in decreasing oxidative stress and metabolic risk factors involved in diabetes and in other chronic diseases. Chitosan-PP60 microspheres prepared by an emulsion cross-linking method were coated with Eudragit S100 to ensure the release of PP60 in the terminal ileum. Different core-coat ratios of Eudragit and chitosan were tested. Optimized chitosan microspheres were obtained with a chitosan:PP60 ratio of 8:1 (Ch-PP608:1), rotation speed of 1500 rpm, and surfactant concentration of 1.0% (m/v) achieving a mean size of 7.16 µm. Their coating with the enteric polymer (S100Ch-PP60) increased the mean size significantly (51.4 µm). The in vitro modified-release of PP60 from S100Ch-PP60 was confirmed in simulated gastrointestinal conditions. Mathematical fitting models were used to characterize the release mechanism showing that both Ch-PP608:1 and S100Ch-PP60 fitted the Korsmeyers-Peppas model. The antioxidant activity of PP60 was kept in glutaraldehyde-crosslinked chitosan microspheres before and after their coating, showing an IC50 of 212.3 µg/mL and 154.4 µg/mL, respectively. The potential of chitosan microspheres for the delivery of catechins was illustrated, with limited risk of cytotoxicity as shown in Caco-2 cell lines using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The beneficial effects of green tea and its derivatives in the management of metabolic disorders can be exploited using mucoadhesive chitosan microspheres coated with enteric polymers for colonic delivery.

Ocular Cell Lines and Genotoxicity Assessment.

Genotoxicity screening tests aim to evaluate if and to what extent a compound in contact with the human body (e.g., a drug molecule, a compound from the environment) interacts with DNA. The comet assay is a sensitive method used to predict the risk of DNA damage in individual cells, as it quantifies the tape breaks, being the alkaline version (pH > 13) the most commonly used in the laboratory. Epithelial cells serve as biomatrices in genotoxicity assessments. As ca. 80% of solid cancers are of epithelial origin, the quantification of the DNA damage upon exposure of epithelial cells to a drug or drug formulation becomes relevant. Comet assays run in epithelial cells also have clinical applications in human biomonitoring, which assesses whether and to what extent is the human body exposed to environmental genotoxic compounds and how such exposure changes over time. Ocular mucosa is particularly exposed to environmental assaults. This review summarizes the published data on the genotoxicity assessment in estimating DNA damage in epithelial cells with a special focus on ocular cell lines. General comet assay procedures for ex vivo and in vivo epithelium samples are also described.

Perillaldehyde 1,2-epoxide Loaded SLN-Tailored mAb: Production, Physicochemical Characterization and In Vitro Cytotoxicity Profile in MCF-7 Cell Lines.

We have developed a new cationic solid lipid nanoparticle (SLN) formulation, composed of Compritol ATO 888, poloxamer 188 and cetyltrimethylammonium bromide (CTAB), to load perillaldehyde 1,2-epoxide, and surface-tailored with a monoclonal antibody for site-specific targeting of human epithelial growth receptor 2 (HER2). Perillaldehyde 1,2-epoxide-loaded cationic SLN (cPa-SLN), with a mean particle size (z-Ave) of 275.31 ± 4.78 nm and polydispersity index (PI) of 0.303 ± 0.081, were produced by high shear homogenization. An encapsulation efficiency of cPa-SLN above 80% was achieved. The release of perillaldehyde 1,2-epoxide from cationic SLN followed the Korsemeyer-Peppas kinetic model, which is typically seen in nanoparticle formulations. The lipid peroxidation of cPa-SLN was assessed by the capacity to produce thiobarbituric acid-reactive substances, while the antioxidant activity was determined by the capacity to scavenge the stable radical DPPH. The surface functionalization of cPa-SLN with the antibody was done via streptavidin-biotin interaction, monitoring z-Ave, PI and ZP of the obtained assembly (cPa-SLN-SAb), as well as its stability in phosphate buffer. The effect of plain cationic SLN (c-SLN, monoterpene free), cPa-SLN and cPa-SLN-SAb onto the MCF-7 cell lines was evaluated in a concentration range from 0.01 to 0.1 mg/mL, confirming that streptavidin adsorption onto cPa-SLN-SAb improved the cell viability in comparison to the cationic cPa-SLN.

Sucupira Oil-Loaded Nanostructured Lipid Carriers (NLC): Lipid Screening, Factorial Design, Release Profile, and Cytotoxicity.

Essential oils are odorant liquid oily products consisting of a complex mixture of volatile compounds obtained from a plant raw material. They have been increasingly proven to act as potential natural agents in the treatment of several human conditions, including diabetes mellitus (DM). DM is a metabolic disorder characterized by chronic hyperglycemia closely related to carbohydrate, protein and fat metabolism disturbances. In order to explore novel approaches for the management of DM our group proposes the encapsulation of sucupira essential oil, obtained from the fruits of the Brazilian plants of the genus Pterodon, in nanostructured lipid carriers (NLCs), a second generation of lipid nanoparticles which act as new controlled drug delivery system (DDS). Encapsulation was performed by hot high-pressure homogenization (HPH) technique and the samples were then analyzed by dynamic light scattering (DLS) for mean average size and polydispersity index (PI) and by electrophoretic light scattering (ELS) for zeta potential (ZP), immediately after production and after 24 h of storage at 4 °C. An optimal sucupira-loaded NLC was found to consist of 0.5% (m/V) sucupira oil, 4.5% (m/V) of Kollivax® GMS II and 1.425% (m/V) of TPGS (formulation no. 6) characterized by a mean particle size ranging from 148.1 ± 0.9815 nm (0 h) to 159.3 ± 9.539 nm (at 24 h), a PI from 0.274 ± 0.029 (0 h) to 0.305 ± 0.028 (24 h) and a ZP from -0.00236 ± 0.147 mV (at 0 h) to 0.125 ± 0.162 (at 24 h). The encapsulation efficiency and loading capacity were 99.98% and 9.6%, respectively. The optimized formulation followed a modified release profile fitting the first order kinetics, over a period of 8 h. In vitro cytotoxicity studies were performed against Caco-2 cell lines, for which the cell viability above 90% confirmed the non-cytotoxic profile of both blank and sucupira oil-loaded NLC.

(+)-Limonene 1,2-Epoxide-Loaded SLNs: Evaluation of Drug Release, Antioxidant Activity, and Cytotoxicity in an HaCaT Cell Line.

In this work, we developed a solid lipid nanoparticle (SLN) formulation with (+)-limonene 1,2-epoxide and glycerol monostearate (Lim-SLNs), stabilized with Poloxamer® 188 in aqueous dispersion to modify the release profile of the loaded monoterpene derivative. We also evaluated the role of SLNs in lipid peroxidation and cytotoxicity in a spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (the HaCaT cell line). For the cell viability assay, the colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used. Lim-SLNs with a loading capacity and encapsulation efficiency of 0.39% and 63%, respectively, were produced by high pressure homogenization. A mean particle size of 194 ± 3.4 nm and polydispersity index of 0.244 were recorded for the loaded Lim-SLNs, as compared to 203 ± 1.5 nm (PI 0.213) for the non-loaded (blank) SLNs. The loading of the monoterpene derivative into glycerol monostearate SLNs fitted into the zero-order kinetics, and ameliorated both lipid peroxidation and cytotoxicity in a keratinocyte cell line. A promising formulation for antioxidant and anti-tumoral activities is here proposed.