Development of clobetasol-loaded biodegradable nanoparticles as an endodontic intracanal medicament.

AIM: The aim of current study is the development and optimization of biodegradable polymeric nanoparticles (NPs) to be used in the field of Endodontics as intracanal medication in cases of avulsed teeth with extended extra-oral time, utilizing PLGA polymers loaded with the anti-inflammatory drug clobetasol propionate (CP). METHODOLOGY: CP-loaded nanoparticles (CP-NPs) were prepared using the solvent displacement method. CP release profile from CP-NPs was assessed for 48 h against free CP. Using extracted human teeth, the degree of infiltration inside the dentinal tubules was studied for both CP-NPs and CP. The anti-inflammatory capacity of CP-NPs was evaluated in vitro measuring their response and reaction against inflammatory cells, in particular against macrophages. The enzyme-linked immunosorbent assay (ELISA) was used to examine the cytokine release of IL-1ß and TNF-α. RESULTS: Optimized CP-NPs displayed an average size below 200 nm and a monomodal population. Additionally, spherical morphology and non-aggregation of CP-NPs were confirmed by transmission electron microscopy. Interaction studies showed that CP was encapsulated inside the NPs and no covalent bonds were formed. Moreover, CP-NPs exhibited a prolonged and steady release with only 21% of the encapsulated CP released after 48 h. Using confocal laser scanning microscopy, it was observed that CP-NPs were able to display enhanced penetration into the dentinal tubules. Neither the release of TNF-α nor IL-1ß increased in CP-NPs compared to the LPS control, displaying results similar and even less than the TCP after 48 h. Moreover, IL-1ß release in LPS-stimulated cells, decreased when macrophages were treated with CP-NPs. CONCLUSIONS: In the present work, CP-NPs were prepared, optimized and characterized displaying significant increase in the degree of infiltration inside the dentinal tubules against CP and were able to significantly reduce TNF-α release. Therefore, CP-NPs constitute a promising therapy for the treatment of avulsed teeth with extended extra-oral time.

Calcium hydroxide-loaded nanoparticles dispersed in thermosensitive gel as a novel intracanal medicament.

AIM: Design, produce and assess the viability of a novel nanotechnological antibacterial thermo-sensible intracanal medicament This involves encapsulating calcium hydroxide (Ca(OH)2) within polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) and dispersing them in a thermosensitive gel (Ca(OH)2-NPs-gel). In addition, perform in vitro and ex vivo assessments to evaluate tissue irritation and penetration capacity into dentinal tubules in comparison to free Ca(OH)2. METHODOLOGY: Reproducibility of Ca(OH)2-NPs was confirmed by obtaining the average size of the NPs, their polydispersity index, zeta potential and entrapment efficiency. Moreover, rheological studies of Ca(OH)2-NPs-gel were carried out with a rheometer, studying the oscillatory stress sweep, the mean viscosity value, frequency and temperature sweeps. Tolerance was assessed using the membrane of an embryonated chicken egg. In vitro Ca(OH)2 release was studied by direct dialysis in an aqueous media monitoring the amount of Ca(OH)2 released. Six extracted human teeth were used to study the depth of penetration of fluorescently labelled Ca(OH)2-NPs-gel into the dentinal tubules and significant differences against free Ca(OH)2 were calculated using one-way anova. RESULTS: Ca(OH)2-NPs-gel demonstrated to be highly reproducible with an average size below 200 nm, a homogeneous NPs population, negative surface charge and high entrapment efficiency. The analysis of the thermosensitive gel allowed us to determine its rheological characteristics, showing that at 10°C gels owned a fluid-like behaviour meanwhile at 37°C they owned an elastic-like behaviour. Ca(OH)2-NPs-gel showed a prolonged drug release and the depth of penetration inside the dentinal tubules increased in the most apical areas. In addition, it was found that this drug did not produce irritation when applied to tissues such as eggs' chorialantoidonic membrane. CONCLUSION: Calcium hydroxide-loaded PLGA NPs dispersed in a thermosensitive gel may constitute a suitable alternative as an intracanal antibacterial medicament.

Extensive colitis associated with ixekizumab.

We present the clinical case of a 56-year-old former smoker female, with a family history of maternal ulcerative colitis and personal history of ankylosing spondylitis treated with Ixekizumab for 3 months, who was admitted for fever, left iliac fossa pain and diarrhea without pathological products of 2 weeks of evolution. Abdominopelvic computed tomography scan identified pancolitis. Complete colonoscopy revealed continuous involvement of the proximal colon (right and transverse colon presented deep ulcerations and mucosal friability) with preservation of the terminal ileum. After many complementary tests and according to the clinical context, the diagnosis of extensive colitis associated with IL-17 inhibitor was established.

Dysphagia secondary to neuroendocrine carcinoma: a rare esophageal tumor.

We present two clinical cases, a 68-year-old male and a 55-year-old female, who are being studied for progressive solid food dysphagia. The initial gastroscopy revealed a polypoid lesion in the first case and a partially stenosing lesion in the second case. Both lesions were located in the mid-esophagus and presented a normal mucosa. Histological diagnosis confirmed an esophageal neuroendocrine carcinoma (NEC) of large cell and small cell types, respectively.

Extraosseous Ewing's sarcoma of the pancreas.

We present the clinical case of a 21-year-old male with abdominal pain in the left hypochondrium radiating to the ipsilateral lumbar area and a weight loss of 2kg over a month, secondary to a large palpable intra-abdominal mass in the examination. TAC revealed a large solid mass with necrotic-cystic component which depended of the pancreas, infiltrated the spleen, enveloped the celiac trunk and affected to the splenic vases. Inmunohistochemical and molecular study confirmed the diagnosis extraosseus Ewing sarcoma (EES).

Psychotropic consumption before and during COVID-19 in Asturias, Spain.

BACKGROUND: Spain as multiple other countries has been experiencing an increasing and sustained trend in the use of psychotropic medications since the mid 90s. Recent studies show public health measures implemented to control SARS-Cov2, such as mobility restrictions and the shutdown of nonessential activities increased mental suffering, even contributing to a higher number of anxiety, depression and insomnia disorders that could lead to an increase in the consumption of psychotropics. The aims were: 1) Evaluate the temporal trend in psychotropic consumption by pharmacological subgroup, sex, and age group 2) Estimate the effect of the COVID-19 pandemic in the use of psychotropic drugs. METHODS: We conducted a retrospective observational study, retrieving all prescriptions of anxiolytics, hypnotics and sedatives, and antidepressants dispensed in pharmacies of Asturias (Northern Spain) for Primary Care patients for the period 2018-2021. We presented the data expressed in Daily Defined Doses (DDDs) for 1000 persons/day (DHD). To estimate changes in DHDs by year and age group we conducted two multiple linear regressions (one for males and one for females) for every pharmacological subgroup studied. Changes were considered statistically significant when the regression coefficient was p < 0.05. We used the Software R 4.1.0. RESULTS: For the studied period, the highest DHDs are for antidepressants, although all of the subgroups experienced an increase in consumption rates. Women consumed more psychotropic drugs than men. In 2021, 372 out of every 1000 women were taking daily 1 DDD of these drugs versus 184 out of every 1000 men. Consumption rates for all psychotropic drugs progressively increases with age. Conversely, the biggest increases in consumption were among the youngest age groups (0-14 and 15-29 years) for women, while for men there is more variability. The regression models suggest an upward trend in psychotropic consumption during all the period, especially remarkable from 2020, for both genders and all age groups. CONCLUSIONS: - The consumption of psychotropic drugs has gradually increased over the last 4 years, with a significant boost starting in 2020 for both sexes, matching the start of the SARS-COV2 pandemic and the implementation of strict Public Health measures to contain it. - The increase observed on children and adolescents is a matter of concern.

Riluzole-Loaded Nanostructured Lipid Carriers for Hyperproliferative Skin Diseases.

Nanocarriers, and especially nanostructured lipid carriers (NLC), represent one of the most effective systems for topical drug administration. NLCs are biodegradable, biocompatible and provide a prolonged drug release. The glutamate release inhibitor Riluzole (RLZ) is a drug currently used for amyotrophic lateral sclerosis (ALS), with anti-proliferative effects potentially beneficial for diseases with excessive cell turnover. However, RLZ possesses low water solubility and high light-sensibility. We present here optimized NLCs loaded with RLZ (RLZ-NLCs) as a potential topical treatment. RLZ-NLCs were prepared by the hot-pressure homogenization method using active essential oils as liquid lipids, and optimized using the design of experiments approach. RLZ-NLCs were developed obtaining optimal properties for dermal application (mean size below 200 nm, negative surface charge and high RLZ entrapment efficacy). In vitro release study demonstrates that RLZ-NLCs allow the successful delivery of RLZ in a sustained manner. Moreover, RLZ-NLCs are not angiogenic and are able to inhibit keratinocyte cell proliferation. Hence, a NLCs delivery system loading RLZ in combination with natural essential oils constitutes a promising strategy against keratinocyte hyperproliferative conditions.

[Use of antibiotics in Paediatric Primary Health Care before and during the COVID-19 pandemic]. / Consumo de antibióticos en Pediatría de Atención Primaria antes y durante la pandemia de COVID-19.

Introduction Consumption of antibiotics is high in Spain, primarily in children. Excessive use of then contributes to the development of antimicrobial resistance. The aim of our study is to analyse the evolution of antibiotic consumption at the Primary Health Care in the paediatric population of Asturias, Spain, from 2014 to 2021, and to evaluate the impact of COVID-19 pandemic on it.Methods Retrospective and observational study using data about antibacterial agents for systemic use dispensed for official prescriptions to children under 14 years in Primary Care. Antibiotic consumption is expressed as defined daily dose (DDD) per 1000 inhabitants per day (DID).Results The antibiotic consumption rate dropped from 13.9 DID in 2014 to 4.0 in 2021 (ß = -1,42, p=0,002), with and inflection point in 2019. From 2019 to 2020 antibiotic use dropped by 47.1%. Antibiotic consumption remained very low from April 2020 to September 2021, and then moderately increased from October 2021. Prevalence of antibiotic use dropped from 39.9% in 2014 to 17.5% in 2021 (ß = -3,64, p=0,006). Relative consumption of amoxicillin/clavulanic acid decreased, while those of amoxiciline and third-generation cephalosporins increased.Conclusions Paediatric antibiotic consumption collapsed in Asturias in 2020, coinciding with COVID-19 pandemic. Monitoring of antimicrobial usage indicators will allow to check if these changes are sustained over time.

Exudative versus Nonexudative Age-Related Macular Degeneration: Physiopathology and Treatment Options.

Age-related macular degeneration (AMD) is an eye disease typically associated with the aging and can be classified into two types-namely, the exudative and the nonexudative AMD. Currently available treatments for exudative AMD use intravitreal injections, which are associated with high risk of infection that can lead to endophthalmitis, while no successful treatments yet exist for the nonexudative form of AMD. In addition to the pharmacologic therapies administered by intravitreal injection already approved by the Food and Drug Administration (FDA) in exudative AMD, there are some laser treatments approved that can be used in combination with the pharmacological therapies. In this review, we discuss the latest developments of treatment options for AMD. Relevant literature available from 1993 was used, which included original articles and reviews available in PubMed database and also information collected from Clinical Trials Gov website using "age-related macular degeneration" and "antiangiogenic therapies" as keywords. The clinical trials search was limited to ongoing trials from 2015 to date.

Novel Strategies against Cancer: Dexibuprofen-Loaded Nanostructured Lipid Carriers.

The aim of this work was to design innovative nanostructured lipid carriers (NLCs) for the delivery of dexibuprofen (DXI) as an antiproliferative therapy against tumoral processes, and overcome its side effects. DXI-NLC samples were prepared with beeswax, Miglyol 812 and Tween 80 using high-pressure homogenization. A two-level factorial design 24 was applied to optimize the formulation, and physicochemical properties such as particle size, zeta potential, polydispersity index and entrapment efficiency were measured. Optimized parameters of DXI-NLCs exhibited a mean particle size of 152.3 nm, a polydispersity index below 0.2, and high DXI entrapment efficiency (higher than 99%). Moreover, DXI-NLCs provided a prolonged drug release, slower than the free DXI. DXI-NLCs were stable for 2 months and their morphology revealed that they possess a spherical shape. In vitro cytotoxicity and anticancer potential studies were performed towards prostate (PC-3) and breast (MDA-MB-468) cancer cell lines. The highest activity of DXI-NLCs was observed towards breast cancer cells, which were effectively inhibited at 3.4 µM. Therefore, DXI-NLCs constitute a promising antiproliferative therapy that has proven to be especially effective against breast cancer.

MAFLD burden on the Spanish National Health System. A call to action.

We have read the editorial by Crespo et al on the metabolic associated liver disease (MAFLD) foreseeable burden on the Spanish National Health System over the next years. Between 0.35-0.4% of Spanish population has cirrhosis and more than one million people has significant fibrosis, assessed by ET ≥ 9 kPa. Compared with general population, patients with cirrhosis have more comorbidities and use healthcare resources more frequently. Recent data show a decrease of 24% in hospitalization due to cirrhosis during the period 2005-2014 in our country. These data predate the availability of direct antiviral agents against HCV. A 20% reduction of cirrhosis-related mortality during the period 2006-2018 was observed, as with other Southern European countries. This decline reflects a reduction of alcohol consumption in the last decades. More recently, 90% of patients with significant liver fibrosis were negative for HCV or HBV, did not consume harmful amounts of alcohol and showed components of metabolic syndrome thereby suggesting that MAFLD is the current leading cause of liver fibrosis in Spain. Some studies found that disadvantaged areas in the Community of Madrid had higher liver-related mortality, highlighting that lower income is another socioeconomic determinant of chronic liver disease.

[Antibiotic consumption in primary care in the adult population of Asturias during 2014-2020 period]. / Consumo de antibióticos en atención primaria en población adulta de Asturias durante el periodo 2014-2020.

Trend study of the consumption of systemic antibiotics in the adult population in of Primary Care of the Health Service of the Principality of Asturias (SESPA) during the period 2014̶2020. Retrospective observational study. SESPA, Primary Care. Population from the Individual Health Card database. Data were collected on the prescription of antibiotics, carried out in the family medicine consultations, dispensed in the pharmacy offices with charge of SESPA. Antibiotic use and consumption variables were analyzed using linear regression models. Prevalence of antibiotic use (population percentage); consumption rate of systemic antibiotics (DTD), relative consumption of narrow-spectrum antibiotics (percentage DDD). The average prevalence of the use of antibiotics for the 2014̶2019 period was 32.2% and 23.9% in 2020. The rate of consumption of systemic antibiotics decreased from 21.4 DTD in 2014 to 12.7 DTD in 2020. The consumption of narrow-spectrum antibiotics remained stable (19.4% DDD in 2014 and 19.3% DDD in 2020) (CI95: -0.10, 0.26). In the period from March to December 2020, the consumption of antibiotics decreased by 28.6% compared to the same period in 2019. In 2014̶2020, the consumption of antibiotics decreased, especially since the COVID-19 pandemic, with stabilization of the consumption of narrow-spectrum antibiotics compared to the total. There is variability in consumption by therapeutic subgroups.

Patient Navigation to Improve Early Access to Supportive Care for Patients with Advanced Cancer in Resource-Limited Settings: A Randomized Controlled Trial.

BACKGROUND: The early integration of supportive care in oncology improves patient-centered outcomes. However, data are lacking regarding how to achieve this in resource-limited settings. We studied whether patient navigation increased access to multidisciplinary supportive care among Mexican patients with advanced cancer. MATERIALS AND METHODS: This randomized controlled trial was conducted between August 2017 and April 2018 at a public hospital in Mexico City. Patients aged ≥18 years with metastatic tumors ≤6 weeks from diagnosis were randomized (1:1) to a patient navigation intervention or usual care. Patients randomized to patient navigation received personalized supportive care from a navigator and a multidisciplinary team. Patients randomized to usual care obtained supportive care referrals from treating oncologists. The primary outcome was the implementation of supportive care interventions at 12 weeks. Secondary outcomes included advance directive completion, supportive care needs, and quality of life. RESULTS: One hundred thirty-four patients were randomized: 67 to patient navigation and 67 to usual care. Supportive care interventions were provided to 74% of patients in the patient navigation arm versus 24% in usual care (difference 0.50, 95% confidence interval [CI] 0.34-0.62; p < .0001). In the patient navigation arm, 48% of eligible patients completed advance directives, compared with 0% in usual care (p < .0001). At 12 weeks, patients randomized to patient navigation had less moderate/severe pain (10% vs. 33%; difference 0.23, 95% CI 0.07-0.38; p = .006), without differences in quality of life between arms. CONCLUSION: Patient navigation improves access to early supportive care, advance care planning, and pain for patients with advanced cancer in resource-limited settings. IMPLICATIONS FOR PRACTICE: The early implementation of supportive care in oncology is recommended by international guidelines, but this might be difficult to achieve in resource-limited settings. This randomized clinical trial including 134 Mexican patients with advanced cancer demonstrates that a multidisciplinary patient navigation intervention can improve the early access to supportive and palliative care interventions, increase advance care planning, and reduce symptoms compared with usual oncologist-guided care alone. These results demonstrate that patient navigation represents a potentially useful solution to achieve the adequate implementation of supportive and palliative care in resource-limited settings globally.

Thymol-loaded PLGA nanoparticles: an efficient approach for acne treatment.

BACKGROUND: Acne is a common skin disorder that involves an infection inside the hair follicle, which is usually treated with antibiotics, resulting in unbalanced skin microbiota and microbial resistance. For this reason, we developed polymeric nanoparticles encapsulating thymol, a natural active compound with antimicrobial and antioxidant properties. In this work, optimization physicochemical characterization, biopharmaceutical behavior and therapeutic efficacy of this novel nanostructured system were assessed. RESULTS: Thymol NPs (TH-NP) resulted on suitable average particle size below 200 nm with a surface charge around - 28 mV and high encapsulation efficiency (80%). TH-NP released TH in a sustained manner and provide a slow-rate penetration into the hair follicle, being highly retained inside the skin. TH-NP possess a potent antimicrobial activity against Cutibacterium acnes and minor effect towards Staphylococcus epidermis, the major resident of the healthy skin microbiota. Additionally, the stability and sterility of developed NPs were maintained along storage. CONCLUSION: TH-NP showed a promising and efficient alternative for the treatment of skin acne infection, avoiding antibiotic administration, reducing side effects, and preventing microbial drug resistance, without altering the healthy skin microbiota. Additionally, TH-NP enhanced TH antioxidant activity, constituting a natural, preservative-free, approach for acne treatment.

Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer's disease: from current to future challenges.

Increasing life expectancy has led to an aging population, which has consequently increased the prevalence of dementia. Alzheimer's disease (AD), the most common form of dementia worldwide, is estimated to make up 50-80% of all cases. AD cases are expected to reach 131 million by 2050, and this increasing prevalence will critically burden economies and health systems in the next decades. There is currently no treatment that can stop or reverse disease progression. In addition, the late diagnosis of AD constitutes a major obstacle to effective disease management. Therefore, improved diagnostic tools and new treatments for AD are urgently needed. In this review, we investigate and describe both well-established and recently discovered AD biomarkers that could potentially be used to detect AD at early stages and allow the monitoring of disease progression. Proteins such as NfL, MMPs, p-tau217, YKL-40, SNAP-25, VCAM-1, and Ng / BACE are some of the most promising biomarkers because of their successful use as diagnostic tools. In addition, we explore the most recent molecular strategies for an AD therapeutic approach and nanomedicine-based technologies, used to both target drugs to the brain and serve as devices for tracking disease progression diagnostic biomarkers. State-of-the-art nanoparticles, such as polymeric, lipid, and metal-based, are being widely investigated for their potential to improve the effectiveness of both conventional drugs and novel compounds for treating AD. The most recent studies on these nanodevices are deeply explained and discussed in this review.

Calcium hydroxide-loaded PLGA biodegradable nanoparticles as an intracanal medicament.

AIM: To develop a formulation in which calcium hydroxide (Ca(OH)2) was successfully loaded into poly(lactic-co-glycolic acid) (PLGA) biodegradable nanoparticles (NPs) to be used in the field of endodontics as an intracanal medicament, including NP optimization and characterization, plus drug release profile of the NPs compared with free Ca(OH)2. Additionally, the depth and area of penetration of the NPs inside the dentinal tubules of extracted teeth were compared with those of the free Ca(OH)2. METHODOLOGY: Ca(OH)2 NPs were prepared using the solvent displacement method. NPs was optimized with a central composite design to obtain a final optimized formulation. The morphology of the NPs was examined under transmission electron microscopy (TEM), and characterization was carried out using X-ray diffraction (XRD), Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC). The drug release profile of the Ca(OH)2 NPs and free Ca(OH)2 was evaluated up to 48 h. Finally, the depth and area of penetration inside the dentinal tubules of extracted teeth were examined for both the Ca(OH)2 NPs and free Ca(OH)2 using the Mann-Whitney U test to determine any significant differences. RESULTS: Utilizing the optimized formulation, the Ca(OH)2 NPs had an average size below 200 nm and polydispersity index lower than 0.2, along with a highly negative zeta potential and suitable entrapment efficiency percentage. The spherical morphology of the Ca(OH)2 NPs was confirmed using TEM. The results of the XRD, FTIR and DSC revealed no interactions and confirmed that the drug was encapsulated inside the NPs. The drug release profile of the Ca(OH)2 NPs exhibited a prolonged steady release that remained stable up to 48 h with higher concentrations than the free Ca(OH)2. After examination by confocal laser scanning microscopy, Ca(OH)2 NPs had a significantly greater depth and area of penetration inside dentinal tubules compared with the free drug. CONCLUSIONS: Ca(OH)2-loaded PLGA NPs were successfully optimized and characterized. The NPs exhibited a prolonged drug release profile and superior penetration inside dentinal tubules of extracted teeth when compared to Ca(OH)2 .

Coordinated assistance plan for the elimination of hepatitis C virus at the centro de ayuda integral al drogodependiente (CAID (Comprehensive Care Centre for Drug Addicts)). / Plan asistencial coordinado para la eliminación del virus de la hepatitis C en el centro de ayuda integral al drogodependiente (CAID).

INTRODUCTION: The drug-injecting population has a high prevalence of hepatitis C virus (HCV) and high risk of transmission. It is a priority to establish an agile diagnostic and treatment plan. OBJECTIVES: 1) Assess the effectiveness of a new coordinated care plan of referral from the Comprehensive Care Centre for Drug Addicts (CAID) to specialised care and 2) Determine the prevalence of HCV, clinical characteristics, effectiveness and safety of treatment in this population. METHODS: 1,300 serologies requested by the CAID between 1998 and 2018 were retrospectively analysed, the seroprevalence of HCV was calculated and the efficiency of the traditional CAID-specialised care referral system was evaluated. A care plan was designed and coordinated among specialists involved in diagnosis and treatment. Since October 2018, 11 patients have been included in the new plan and the performance of both referral systems was compared. RESULTS: With the traditional system, 48.2% (83/172) of the patients were lost. 14.5% (172/1,300) presented positive HCV serology, compared to the general population OR = 19; 95% CI 14.3-25. The prevalence of active infection was 80.3% (90/112). The prevalence of active infection was 80.3% (90/112). Of the 11 patients referred by the new plan, 76.9% (8/11) had active infection and 100% (8/8) were treated with Direct Antiviral Agents successfully. CONCLUSIONS: The new coordinated CAID-specialised care plan presents high effectiveness in comparison with the traditional referral system. The seroprevalence and prevalence of active infection in the CAID population is very high. Treatments with Direct Antiviral Agents are effective and safe.

State-of-the-art polymeric nanoparticles as promising therapeutic tools against human bacterial infections.

Infectious diseases kill over 17 million people a year, among which bacterial infections stand out. From all the bacterial infections, tuberculosis, diarrhoea, meningitis, pneumonia, sexual transmission diseases and nosocomial infections are the most severe bacterial infections, which affect millions of people worldwide. Moreover, the indiscriminate use of antibiotic drugs in the last decades has triggered an increasing multiple resistance towards these drugs, which represent a serious global socioeconomic and public health risk. It is estimated that 33,000 and 35,000 people die yearly in Europe and the United States, respectively, as a direct result of antimicrobial resistance. For all these reasons, there is an emerging need to find novel alternatives to overcome these issues and reduced the morbidity and mortality associated to bacterial infectious diseases. In that sense, nanotechnological approaches, especially smart polymeric nanoparticles, has wrought a revolution in this field, providing an innovative therapeutic alternative able to improve the limitations encountered in available treatments and capable to be effective by theirselves. In this review, we examine the current status of most dangerous human infections, together with an in-depth discussion of the role of nanomedicine to overcome the current disadvantages, and specifically the most recent and innovative studies involving polymeric nanoparticles against most common bacterial infections of the human body.

First steps in the formulation of praziquantel nanosuspensions for pharmaceutical applications.

Praziquantel (PZQ), a broad spectrum anthelmintic drug, cannot be found in acceptable dosage forms for elderly patients, paediatric patients, and for veterinary use. In fact, very little has been done up to now in the formulation of liquid dosage forms, being they always formulated for parenteral administration. To beat this important challenge, it was accomplished a comprehensive analysis of the influence of two elementary physicochemical aspects, i.e. surface thermodynamic and electrokinetic properties, on the colloidal stability of PZQ nanosuspensions. The hydrophobic character of the drug, intensely determining the flocculation curves, was confirmed by the thermodynamic characterization. The electrophoretic characterization, in combination with the sedimentation and relative absorbance versus time curves, highlighted that the electrical double layer thickness and the surface charge can play an essential role in the stability of the pharmaceutical colloid. Finally, it was demonstrated that controlling the pH values and the incorporation of electrolytes can help in formulating PZQ aqueous nanosuspensions with appropriate stability and redispersibility behaviours for pharmaceutical use.

Vasculogenic mimicry-associated ultrastructural findings in human and canine inflammatory breast cancer cell lines.

BACKGROUND: Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most lethal mammary cancers. An exacerbated angiogenesis and the existence of vasculogenic mimicry (VM) are hallmarks of these tumors. The information regarding VM and ultrastructural characteristics of mammary cell lines is scant. METHODS: In this study, IBC cell line SUM149 and IMC cell line IPC-366 in adherent (2D) and non-adherent (3D) (mammospheres, cancer stem cells) conditions were analyzed by transmission and scanning electron microscopy (TEM and SEM, respectively). RESULTS: The TEM revealed round to oval shape cells with microvilli on the surface, high numbers of peroxisomes in close apposition to lipid droplets and some extracellular derived vesicles. The TEM and the SEM mammospheres revealed group of cells clumping together with a central lumen (resembling a mammary acini). The cells joint are tight junctions and zonula adherens. By SEM two cell morphologies were observed: spherical and flattened cells. There was evidence endothelial-like cells (ELCs), which is characteristic for this disease, showing several or unique cytoplasmic empty space. ELCs were more frequent in 3D than in 2D culture conditions and contained Weibel-Palade cytoplasmic bodies, which are exclusive structures of endothelial cells. CONCLUSIONS: Both cell lines, IPC-366 and SUM-149, shared ultrastructural characteristics, further supporting canine IMC as a model for the human disease. To the best of our knowledge, this is the first study that demonstrate the morphological differentiation of cultured cancer stem cells from cancer epithelial cell lines into endothelial-like cells, confirming the vasculogenic mimicry phenomenon from an ultrastructural point of view.