Delivery of Therapeutic Biopolymers Employing Silica-Based Nanosystems.

The use of nanoparticles is crucial for the development of a new generation of nanodevices for clinical applications. Silica-based nanoparticles can be tailored with a wide range of functional biopolymers with unique physicochemical properties thus providing several advantages: (1) limitation of interparticle interaction, (2) preservation of cargo and particle integrity, (3) reduction of immune response, (4) additional therapeutic effects and (5) cell targeting. Therefore, the engineering of advanced functional coatings is of utmost importance to enhance the biocompatibility of existing biomaterials. Herein we will focus on the most recent advances reported on the delivery and therapeutic use of silica-based nanoparticles containing biopolymers (proteins, nucleotides, and polysaccharides) with proven biological effects.

Socioeconomic impact and burden of hypertension in the Philippines projected in 2050.

Hypertension has remained the number one cause of cardiovascular death in the Philippines for over three (3) decades. Despite this finding, the burden accounted for by hypertension is investigated to a lesser extent. We performed this study to determine the socioeconomic impact of hypertension in the Philippines, and it was projected in the next 30 years. We gathered primary data through interviews, Labor Force Survey (N = 806), and secondary data from various government published reports. The cost of illness (COI) was calculated using the direct morbidity and mortality costs. The impact (% of respondents) of uncontrolled hypertension on productivity at work showed the following; four (4) days missing work (72%) and ten (10) days lost of productivity (63%). The impact (% of respondents) of uncontrolled hypertension on productivity at home showed the following: six (6) days of household suspended (66%), eleven (11) days reduced household work (78%), and five (5) days affected social activity (60%). The productivity loss of premature mortality accounts for 17% of the total economic burden in 2020 and will increase to 20% by 2050. In 2020, 70% of the total economic burden was accounted for direct & indirect care. At its present value, the economic cost of hypertension is expected to increase from US$1 billion in 2020 to US$1.9 billion by 2050. The socioeconomic impact of uncontrolled hypertension in the Philippines was enormous, challenging, and overwhelming for the next 30 years.

Superparamagnetic Iron Oxide Nanoparticles Decorated Mesoporous Silica Nanosystem for Combined Antibiofilm Therapy.

A crucial challenge to face in the treatment of biofilm-associated infection is the ability of bacteria to develop resistance to traditional antimicrobial therapies based on the administration of antibiotics alone. This study aims to apply magnetic hyperthermia together with controlled antibiotic delivery from a unique magnetic-responsive nanocarrier for a combination therapy against biofilm. The design of the nanosystem is based on antibiotic-loaded mesoporous silica nanoparticles (MSNs) externally functionalized with a thermo-responsive polymer capping layer, and decorated in the outermost surface with superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs are able to generate heat upon application of an alternating magnetic field (AMF), reaching the temperature needed to induce a change in the polymer conformation from linear to globular, therefore triggering pore uncapping and the antibiotic cargo release. The microbiological assays indicated that exposure of E. coli biofilms to 200 µg/mL of the nanosystem and the application of an AMF (202 kHz, 30 mT) decreased the number of viable bacteria by 4 log10 units compared with the control. The results of the present study show that combined hyperthermia and antibiotic treatment is a promising approach for the effective management of biofilm-associated infections.

May Measurement Month 2019: an analysis of blood pressure screening results in the Philippines.

The Philippine Society of Hypertension (PSH) took part again in the annual May Measurement Month 2019 (MMM19) blood pressure (BP) measurement campaign to raise awareness of hypertension especially in those who are not aware of their condition. The MMM19 standard protocol designed by the International Society of Hypertension was used during screening. These included the collection of basic data on demography, lifestyle, and environmental factors. Standardized sitting BP measurements were taken two to three times, using an automated BP apparatus and were inputted either in the MMM19 app or data were recorded in paper form and manually transferred to Excel spreadsheets by encoders supervised by the PSH. A total of 89 941 participated through opportunistic convenience sampling. After multiple imputation, a total of 47 925 (53.3%) participants had hypertension (≥140/90 mmHg or on antihypertensive medication). Of this number, 31 151 (65%) were aware that they had high BP and 30 120 (62.8%) were on antihypertensive medications. Of the 30 120 participants on antihypertensive medications, only 18 373 (61.1%) had controlled BP (<140/90 mmHg). Being overweight or obese were significant predictors of high BP. Other predictors of high systolic BP and diastolic BP were alcohol intake, smoking, and a previous history of hypertension in pregnancy, while pregnant participants had significantly lower BP. The MMM19 campaign succeeded in raising awareness of high BP in our country, and the opportunistic sampling enhanced a sense of people empowerment by their knowing how easy it is to detect high BP and thereby enabling the prevention of long-term health complications. The higher BP control in the MMM19 hypertensive individuals possibly attests to the success of the previous MMM17 and MMM18 campaigns.

Recent Advances Toward the Use of Mesoporous Silica Nanoparticles for the Treatment of Bacterial Infections.

It is a fact that the use of antibiotics is inducing a growing resistance on bacteria. This situation is not only the consequence of a drugs' misuse, but a direct consequence of a widespread and continuous use. Current studies suggest that this effect could be reversed by using abandoned antibiotics to which bacteria have lost their resistance, but this is only a temporary solution that in near future would lead to new resistance problems. Fortunately, current nanotechnology offers a new life for old and new antibiotics, which could have significantly different pharmacokinetics when properly delivered; enabling new routes able to bypass acquired resistances. In this contribution, we will focus on the use of porous silica nanoparticles as functional carriers for the delivery of antibiotics and biocides in combination with additional features like membrane sensitizing and heavy metal-driven metabolic-disrupting therapies as two of the most interesting combination therapies.

Emerging Strategies in Anticancer Combination Therapy Employing Silica-Based Nanosystems.

Combination therapy has emerged as one of the most promising approaches for cancer treatment. However, beyond remotely-triggered therapies that require advanced infrastructures and optimization, new combination therapies based on internally triggered cell-killing effects have also demonstrated promising therapeutic profiles. In this revision, the focus is on self-triggered strategies able to improve the therapeutic effect of drug delivery nanosystems. As reviewed, ferroptosis, hypoxia, and immunotherapy show potency enough to treat satisfactorily tumors in vivo. However, the interest of combining those with chemotherapeutics, especially with carriers based on mesoporous silica, has provided a new generation of therapeutic nanomedicines with potential enough to achieve complete tumor remission in murine models.

Production of MCM-41 Nanoparticles with Control of Particle Size and Structural Properties: Optimizing Operational Conditions during Scale-Up.

The synthesis of Mobil Composition of Matter 41 (MCM-41) mesoporous silica nanoparticles (MSNs) of controlled sizes and porous structure has been performed at laboratory and pilot plant scales. Firstly, the effects of the main operating conditions (TEOS -Tetraethyl ortosilicate- addition rate, nanoparticle maturation time, temperature, and CTAB -Cetrimonium bromide- concentration) on the synthesis at laboratory scale (1 L round-bottom flask) were studied via a Taguchi experimental design. Subsequently, a profound one-by-one study of operating conditions was permitted to upscale the process without significant particle enlargement and pore deformation. To achieve this, the temperature was set to 60 °C and the CTAB to TEOS molar ratio to 8. The final runs were performed at pilot plant scale (5 L cylindrical reactor with temperature and stirring speed control) to analyze stirring speed, type of impeller, TEOS addition rate, and nanoparticle maturation time effects, confirming results at laboratory scale. Despite slight variations on the morphology of the nanoparticles, this methodology provided MSNs with adequate sizes and porosities for biomedical applications, regardless of the reactor/scale. The process was shown to be robust and reproducible using mild synthesis conditions (2 mL⋅min-1 TEOS addition rate, 400 rpm stirred by a Rushton turbine, 60 min maturation time, 60 °C, 2 g⋅L-1 CTAB, molar ratio TEOS/CTAB = 8), providing ca. 13 g of prismatic short mesoporous 100-200 nm nanorods with non-connected 3 nm parallel mesopores.

May Measurement Month 2018: an analysis of blood pressure screening in the Philippines.

Building on the gains of May Measurement Month 2017 (MMM17), the Philippine Society of Hypertension once again took part in MMM18 to raise awareness of high blood pressure (BP) in the country and to harness opportunistic BP screening in detecting unaware hypertensive individuals and referring them for treatment. We followed the standard MMM18 protocol designed by the International Society of Hypertension, utilizing convenience sampling with volunteer investigators, taking three sitting BP measurements of volunteer adults (≥18 years). Basic data on demographic, lifestyle, and environmental factors were also taken. We analysed 177 176 screened individuals from the Philippines. Of these, 29.1% (51 527) had also participated in MMM17, whereas 68.8% (121 893) were new screenees; and 14.2% (25 232) had their BP taken for the first time ever. After multiple imputation, 39.0% (69 126) were hypertensive. Of these, 50.3% (34 795) were aware they were hypertensive. 49.9% (34 491) were on antihypertensive medication, 58.0% (20 010) of whom had controlled BP <140/90 mmHg. Only 28.9% of all participants with hypertension had controlled BP. Systolic BPs and diastolic BPs were significantly higher in the overweight and obese, in those receiving antihypertensive medications, in patients with diabetes, and significantly lower in pregnant women. MMM18 has again shown that opportunistic BP screening, harnessing volunteers, is a pragmatic public health measure to improve awareness and treatment rates of raised BP.

The Association of Febuxostat Compared With Allopurinol on Blood Pressure and Major Adverse Cardiac Events Among Adult Patients With Hyperuricemia: A Meta-analysis.

Increased uric acid levels have been known to be associated with different cardiovascular and renal diseases. Over the past few years, several studies have examined the role of urate-lowering therapy (ULT) in hypertension and major adverse cardiac events (MACE) and suggest a potential role of elevated serum uric acid as an independent cardiovascular risk factor. This meta-analysis was done to determine the association of 2 ULTs commonly used in clinical practice (febuxostat vs. allopurinol) on hypertension and MACE and resolve the conflicting results of the outcomes of earlier studies. Randomized controlled trials comparing febuxostat versus allopurinol published with outcomes on blood pressure, all-cause mortality, myocardial infarction (MI), and stroke were searched through PubMed, Google Scholar, and Cochrane database. A total of 10 studies were subsequently included in the meta-analysis. Pooled analysis of the mean differences (MD) were done for the outcomes on blood pressure (systolic and diastolic) and risk ratios (RRs) for the outcomes on MACE with corresponding 95% confidence intervals (CIs). Pooled analysis of studies on hyperuricemic patients showed that febuxostat 40 mg has no significant difference compared with allopurinol 100/300 mg with respect to diastolic (MD, -0.56 with 95% CI of -4.28 to 3.15) and systolic blood pressure (MD, 0.30 with 95% CI of -3.33 to 3.93). No significant differences were also noted on all-cause mortality (RR, 1.18 with 95% CI of 0.99-1.41), MI (RR, 0.92 with 95% CI of 0.72-1.18), and stroke (RR, 1.05 with 95% CI of 0.77-1.43). The results of this meta-analysis showed that the 2 ULTs (febuxostat vs. allopurinol) have no significant association with respect to blood pressure among adult patients with hyperuricemia. No significant association was also noted of either ULT with all-cause mortality, MI, and stroke.

Mesoporous Silica Nanoparticles as Carriers for Therapeutic Biomolecules.

The enormous versatility of mesoporous silica nanoparticles permits the creation of a large number of nanotherapeutic systems for the treatment of cancer and many other pathologies. In addition to the controlled release of small drugs, these materials allow a broad number of molecules of a very different nature and sizes. In this review, we focus on biogenic species with therapeutic abilities (proteins, peptides, nucleic acids, and glycans), as well as how nanotechnology, in particular silica-based materials, can help in establishing new and more efficient routes for their administration. Indeed, since the applicability of those combinations of mesoporous silica with bio(macro)molecules goes beyond cancer treatment, we address a classification based on the type of therapeutic action. Likewise, as illustrative content, we highlight the most typical issues and problems found in the preparation of those hybrid nanotherapeutic materials.

A systematic review and meta-analysis on the effectiveness of an invasive strategy compared to a conservative approach in patients > 65 years old with non-ST elevation acute coronary syndrome.

BACKGROUND: Patients 65 years old and older largely represent (>50%) hospital-admitted patients with acute coronary syndrome (ACS). Data are conflicting comparing efficacy of early routine invasive (within 48-72 hours of initial evaluation) versus conservative management of ACS in this population. OBJECTIVE: We aimed to determine the effectiveness of routine early invasive strategy compared to conservative treatment in reducing major adverse cardiovascular events in patients 65 years old and older with non-ST elevation (NSTE) ACS. DATA SOURCES: We conducted a systematic review of randomized controlled trials (RCTs) through PubMed, Cochrane, and Google Scholar database. STUDY SELECTION: The studies included were RCTs that evaluated the effectiveness of invasive strategy compared to conservative treatment among patients ≥ 65 years old diagnosed with NSTEACS. Studies were included if they assessed any of the following outcomes of death, cardiovascular mortality, myocardial infarction (MI), stroke, recurrent angina, and need for revascularization. Six articles were subsequently included in the meta-analysis. DATA EXTRACTION: Three independent reviewers extracted the data of interest from the articles using a standardized data collection form that included study quality indicators. Disparity in assessment was adjudicated by another reviewer. DATA SYNTHESIS: All pooled analyses were initially done using Fixed Effects model. For pooled analyses with significant heterogeneity (I2≥ 50%), the Random Effects model was used. A total of 3,768 patients were included, 1,986 in the invasive strategy group, and 1,782 in the conservative treatment group. RESULTS: Meta-analysis showed less incidence of revascularization in the invasive (2%) over conservative treatment groups (8%), with overall risk ratio of 0.29 (95% CI 0.14 to 0.59). Across all pooled studies, no significant effect of invasive strategy on all-cause mortality, cardiovascular mortality, stroke, and MI was observed. Only one study assessed the outcome of recurrent angina. CONCLUSION: There was a significantly lower rate of revascularization in the invasive strategy group compared to the conservative treatment group. In the reduction of all-cause mortality, cardiovascular mortality, MI, and stroke there was no significant effect of invasive strategy versus conservative treatment. This finding does not support the bias against early routine invasive intervention in patients ≥ 65 years old with NSTEACS. Further studies focusing on these patients with larger population sizes are still needed.

May Measurement Month 2017: Results of 39 national blood pressure screening programmes.

Raised blood pressure is the biggest single risk factor responsible for mortality worldwide. Despite this, the majority of people with hypertension are unaware of having it, are untreated, or are on treatment but uncontrolled. May Measurement Month is a global campaign initiated by the International Society of Hypertension with the aim of raising awareness of high blood pressure. In the first year of the campaign in 2017, over 1.2 million people were screened in 80 countries across the world, finding over 100 000 people with hypertension who were not on treatment and over 150 000 people on anti-hypertensive treatment who were not controlled. The individual national results from 39 countries are presented in this supplement. In this article, we discuss the background to the campaign, along with some of the logistical and methodological challenges that were faced in setting up the campaign, and in collecting and analysing the data from such a large cross-sectional study. With the lessons learned from the 2017 campaign, the campaign was repeated in 2018 and is to be repeated again in 2019.

May Measurement Month 2017: an analysis of blood pressure screening in the Philippines-South-East Asia and Australasia.

Cardiovascular diseases remain the Philippines' leading cause of mortality, with hypertension as a prevalent contributory risk factor. We took part in May Measurement Month 2017 (MMM17), a global initiative to raise awareness of high blood pressure (BP) and to serve as a temporary solution to the lack of screening programs worldwide. Following the standard MMM protocol, data for 271 604 screened individuals were submitted from the Philippines. After multiple imputation, 91 994 (34.3%) were hypertensive; 28 662 out of 205 158 participants (14.0%) not receiving treatment had hypertension; and of the 60 370 receiving treatment, 25 144 (41.6%) had uncontrolled BP. Blood pressures were significantly higher in the overweight and obese, current smokers, in participants receiving antihypertensive medication, those with previous myocardial infarction or stroke. The BP measurements were relatively lower when taken on the left arm, and in pregnant women. A slightly higher systolic BP was noted in participants who reported no alcohol intake. Blood pressures recorded during the weekends were highest, and the lowest readings were obtained on Tuesdays. MMM17 was the largest BP screening campaign conducted in the Philippines. Opportunistic BP screening, harnessing volunteers, are a cost-effective public health measure to improve awareness and treatment rates of raised BP. These may help provide additional information that can guide medical practitioners and health officials in drafting preventive and therapeutic measures to improve control rates and long-term outcomes of hypertensive individuals in the population.

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension.

AIMS: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. METHODS AND RESULTS: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. CONCLUSION: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.

Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update.

INTRODUCTION: Mesoporous silica nanoparticles (MSNs) are outstanding nanoplatforms for drug delivery. Herein, the most recent advances to turn MSN-based carriers into minimal side effect drug delivery agents are covered. AREAS COVERED: This review summarizes the scientific advances dealing with MSNs for targeted and stimuli-responsive drug delivery since 2015. Delivery aspects to diseased tissues together with approaches to obtain smart MSNs able to respond to internal or external stimuli and their applications are here described. Special emphasis is done on the combination of two or more stimuli on the same nanoplatform and on combined drug therapy. EXPERT OPINION: The use of MSNs in nanomedicine is a promising research field because they are outstanding platforms for treating different pathologies. This is possible thanks to their structural, chemical, physical and biological properties. However, there are certain issues that should be overcome to improve the suitability of MSNs for clinical applications. All materials must be properly characterized prior to their in vivo evaluation; furthermore, preclinical in vivo studies need to be standardized to demonstrate the MSNs clinical translation potential.

Functional Mesoporous Silica Nanocomposites: Biomedical applications and Biosafety.

The rise and development of nanotechnology has enabled the creation of a wide number of systems with new and advantageous features to treat cancer. However, in many cases, the lone application of these new nanotherapeutics has proven not to be enough to achieve acceptable therapeutic efficacies. Hence, to avoid these limitations, the scientific community has embarked on the development of single formulations capable of combining functionalities. Among all possible components, silica-either solid or mesoporous-has become of importance as connecting and coating material for these new-generation therapeutic nanodevices. In the present review, the most recent examples of fully inorganic silica-based functional composites are visited, paying particular attention to those with potential biomedical applicability. Additionally, some highlights will be given with respect to their possible biosafety issues based on their chemical composition.

Molecular Scaffolds as Double-Targeting Agents For the Diagnosis and Treatment of Neuroblastoma.

The selective delivery of therapeutic and imaging agents to tumoral cells has been postulated as one of the most important challenges in the nanomedicine field. Meta-iodobenzilguanidine (MIBG) is widely used for the diagnosis of neuroblastoma (NB) due to its strong affinity for the norepinephrine transporter (NET), usually overexpressed on the membrane of malignant cells. Herein, a family of novel Y-shaped scaffolds has been synthesized, which have structural analogues of MIBG covalently attached at each end of the Y-structure. The cellular uptake capacity of these double-targeting ligands has been evaluated in vitro and in vivo, yielding one specific Y-shaped structure that is able to be engulfed by the malignant cells, and accumulates in the tumoral tissue, at significantly higher levels than the structure containing only one single targeting agent. This Y-shaped ligand can provide a powerful tool for the current treatment and diagnosis of this disease.

Building Block Based Construction of Membrane-Organelle Double Targeted Nanosystem for Two-Drug Delivery.

Despite the claim that encapsulation of drugs improves the therapeutic profile of free drugs, there are still important limitations in drug delivery. With respect to cancer treatment, two promising implementations are combination therapy and targeted devices, which are aimed at increasing the drug effect either by achieving higher cell death rates or by discriminating between cell populations. However, for the time being, the scope of combining both approaches is unknown. To advance this knowledge, a two-drug-delivery system with dual cell-organelle targeting based on mesoporous silica nanoparticles, which are known to be able to host drugs within their pores, has been designed. In vitro results show a synergistic effect and high efficacy, demonstrating that the combination of dual therapy and targeting could still advance the development of drug-delivery nanodevices against difficult-to-treat cancers.

May Measurement Month 2017: an analysis of blood pressure screening results worldwide.

BACKGROUND: Increased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screening programmes. METHODS: This cross-sectional survey included volunteer adults (≥18 years) who ideally had not had their blood pressures measured in the past year. Each participant had their blood pressure measured three times and received a a questionnaire about demographic, lifestyle, and environmental factors. The primary objective was to raise awareness of blood pressure, measured by number of countries involved, number of people screened, and number of people who have untreated or inadequately treated hypertension (defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, or on the basis of receiving antihypertensive medication). Multiple imputation was used to estimate the mean of the second and third blood pressure readings if these were not recorded. Measures of association were analysed using linear mixed models. FINDINGS: Data were collected from 1 201 570 individuals in 80 countries. After imputation, of the 1 128 635 individuals for whom a mean of the second and third readings was available, 393 924 (34·9%) individuals had hypertension. 153 905 (17·3%) of 888 616 individuals who were not receiving antihypertensive treatment were hypertensive, and 105 456 (46·3%) of the 227 721 individuals receiving treatment did not have controlled blood pressure. Significant differences in adjusted blood pressures and hypertension prevalence were apparent between regions. Adjusted blood pressure was higher in association with antihypertensive medication, diabetes, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm than on the left arm, and blood pressure was highest on Saturdays. INTERPRETATION: Inexpensive global screening of blood pressure is achievable using volunteers and convenience sampling. Pending the set-up of systematic surveillance systems worldwide, MMM will be repeated annually to raise awareness of blood pressure. FUNDING: International Society of Hypertension, Centers for Disease Control and Prevention, Servier Pharmaceutical Co.