Functionalization of gold nanostars with cationic ß-cyclodextrin-based polymer for drug co-loading and SERS monitoring

Gold nanostars (AuNSs) exhibit modulated plasmon resonance and have a high SERS enhancement factor. However, their low colloidal stability limits their biomedical application as a nanomaterial. Cationic ß-cyclodextrin-based polymer (CCD/P) has low cytotoxicity, can load and transport drugs more efficiently than the corresponding monomeric form, and has an appropriate cationic group to stabilize gold nanoparticles. In this work, we functionalized AuNSs with CCD/P to load phenylethylamine (PhEA) and piperine (PIP) and evaluated SERS-based applications of the products. PhEA and PIP were included in the polymer and used to functionalize AuNSs, forming a new AuNS-CCD/P-PhEA-PIP nanosystem. The system was characterized by UV–VIS, IR, and NMR spectroscopy, TGA, SPR, DLS, zeta potential analysis, FE-SEM, and TEM. Additionally, Raman optical activity, SERS analysis and complementary theoretical studies were used for characterization. Minor adjustments increased the colloidal stability of AuNSs. The loading capacity of the CCD/P with PhEA-PIP was 95 ± 7%. The physicochemical parameters of the AuNS-CCD/P-PhEA-PIP system, such as size and Z potential, are suitable for potential biomedical applications Raman and SERS studies were used to monitor PhEA and PIP loading and their preferential orientation upon interaction with the surface of AuNSs. This unique nanomaterial could be used for simultaneous drug loading and SERS-based detection

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30–79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30–79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306–359) million women and 317 (292–344) million men in 1990 to 626 (584–668) million women and 652 (604–698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55–62) of women and 49% (46–52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43–51) of women and 38% (35–41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20–27) for women and 18% (16–21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings

β-Cyclodextrin-Based Nanosponges Functionalized with Drugs and Gold Nanoparticles

Drugs are widely used as therapeutic agents; however, they may present some limitations. To overcome some of the therapeutic disadvantages of drugs, the use of β-cyclodextrin-based nanosponges (βCDNS) constitutes a promising strategy. βCDNS are matrices that contain multiple hydrophobic cavities, increasing the loading capacity, association, and stability of the included drugs. On the other hand, gold nanoparticles (AuNPs) are also used as therapeutic and diagnostic agents due to their unique properties and high chemical reactivity. In this work, we developed a new nanomaterial based on βCDNS and two therapeutic agents, drugs and AuNPs. First, the drugs phenylethylamine (PhEA) and 2-amino-4-(4-chlorophenyl)-thiazole (AT) were loaded on βCDNS. Later, the βCDNS–drug supramolecular complexes were functionalized with AuNPs, forming the βCDNS–PhEA–AuNP and βCDNS–AT–AuNP systems. The success of the formation of βCDNS and the loading of PhEA, AT, and AuNPs was demonstrated using different characterization techniques. The loading capacities of PhEA and AT in βCDNS were 90% and 150%, respectively, which is eight times higher than that with native βCD. The functional groups SH and NH2 of the drugs remained exposed and allowed the stabilization of the AuNPs, 85% of which were immobilized. These unique systems can be versatile materials with an efficient loading capacity for potential applications in the transport of therapeutic agents

Cyclodextrin-modified nanomaterials for drug delivery: Classification and advances in controlled release and bioavailability

In drug delivery, one widely used way of overcoming the biopharmaceutical problems present in several active pharmaceutical ingredients, such as poor aqueous solubility, early instability, and low bioavailability, is the formation of inclusion compounds with cyclodextrins (CD). In recent years, the use of CD derivatives in combination with nanomaterials has shown to be a promising strategy for formulating new, optimized systems. The goals of this review are to give in-depth knowledge and critical appraisal of the main CD-modified or CD-based nanomaterials for drug delivery, such as lipid-based nanocarriers, natural and synthetic polymeric nanocarriers, nanosponges, graphene derivatives, mesoporous silica nanoparticles, plasmonic and magnetic nanoparticles, quantum dots and other miscellaneous systems such as nanovalves, metal-organic frameworks, Janus nanoparticles, and nanofibers. Special attention is given to nanosystems that achieve controlled drug release and increase their bioavailability during in vivo studies.Fil: Real, Daniel Andrés. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Real, Daniel Andrés. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Bolaños, Karen. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Bolaños, Karen. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Bolaños, Karen. Universidad de Chile. Facultad de Medicina. Center for Studies on Exercise, Metabolism and Cancer. Cellular Communication Laboratory. Program of Cellular and Molecular Biology; Chile.Fil: Priotti, Josefina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Técnica Farmacéutica; Argentina.Fil: Yutronic, Nicolás. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química. Laboratorio de Nanoquímica y Química Supramolecular; Chile.Fil: Kogan, Marcelo J. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Kogan, Marcelo J. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Sierpe, Rodrigo. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Sierpe, Rodrigo. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Sierpe, Rodrigo. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química. Laboratorio de Nanoquímica y Química Supramolecular; Chile.Fil: Sierpe, Rodrigo. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Biosensores; Chile.Fil: Donoso González, Orlando. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Donoso González, Orlando. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Donoso González, Orlando. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química. Laboratorio de Nanoquímica y Química Supramolecular; Chile

Solid-State Formation of a Potential Melphalan Delivery Nanosystem Based on β-Cyclodextrin and Silver Nanoparticles

Melphalan (Mel) is an antineoplastic widely used in cancer and other diseases. Its low solubility, rapid hydrolysis, and non-specificity limit its therapeutic performance. To overcome these disadvantages, Mel was included in β-cyclodextrin (βCD), which is a macromolecule that increases its aqueous solubility and stability, among other properties. Additionally, the βCD–Mel complex has been used as a substrate to deposit silver nanoparticles (AgNPs) through magnetron sputtering, forming the βCD–Mel–AgNPs crystalline system. Different techniques showed that the complex (stoichiometric ratio 1:1) has a loading capacity of 27%, an association constant of 625 M−1, and a degree of solubilization of 0.034. Added to this, Mel is partially included, exposing the NH2 and COOH groups that stabilize AgNPs in the solid state, with an average size of 15 ± 3 nm. Its dissolution results in a colloidal solution of AgNPs covered by multiple layers of the βCD–Mel complex, with a hydrodynamic diameter of 116 nm, a PDI of 0.4, and a surface charge of 19 mV. The in vitro permeability assays show that the effective permeability of Mel increased using βCD and AgNPs. This novel nanosystem based on βCD and AgNPs is a promising candidate as a Mel nanocarrier for cancer therapy

Optimizing Dacarbazine Therapy: Design of a Laser-Triggered Delivery System Based on β-Cyclodextrin and Plasmonic Gold Nanoparticles

Dacarbazine (DB) is an antineoplastic drug extensively used in cancer therapy. However, present limitations on its performance are related to its low solubility, instability, and non-specificity. To overcome these drawbacks, DB was included in β-cyclodextrin (βCD), which increased its aqueous solubility and stability. This new βCD@DB complex has been associated with plasmonic gold nanoparticles (AuNPs), and polyethylene glycol (PEG) has been added in the process to increase the colloidal stability and biocompatibility. Different techniques revealed that DB allows for a dynamic inclusion into βCD, with an association constant of 80 M−1 and a degree of solubilization of 0.023, where βCD showed a loading capacity of 16%. The partial exposure of the NH2 group in the included DB allows its interaction with AuNPs, with a loading efficiency of 99%. The PEG-AuNPs-βCD@DB nanosystem exhibits an optical plasmonic absorption at 525 nm, a surface charge of −29 mV, and an average size of 12 nm. Finally, laser irradiation assays showed that DB can be released from this platform in a controlled manner over time, reaching a concentration of 56 μg/mL (43% of the initially loaded amount), which, added to the previous data, validates its potential for drug delivery applications. Therefore, the novel nanosystem based on βCD, AuNPs, and PEG is a promising candidate as a new nanocarrier for DB

Iron-Reduced Graphene Oxide Core–Shell Micromotors Designed for Magnetic Guidance and Photothermal Therapy under Second Near-Infrared Light

Core–shell micro/nanomotors have garnered significant interest in biomedicine owing to their versatile task-performing capabilities. However, their effectiveness for photothermal therapy (PTT) still faces challenges because of their poor tumor accumulation, lower light-to-heat conversion, and due to the limited penetration of near-infrared (NIR) light. In this study, we present a novel core–shell micromotor that combines magnetic and photothermal properties. It is synthesized via the template-assisted electrodeposition of iron (Fe) and reduced graphene oxide (rGO) on a microtubular pore-shaped membrane. The resulting Fe-rGO micromotor consists of a core of oval-shaped zero-valent iron nanoparticles with large magnetization. At the same time, the outer layer has a uniform reduced graphene oxide (rGO) topography. Combined, these Fe-rGO core–shell micromotors respond to magnetic forces and near-infrared (NIR) light (1064 nm), achieving a remarkable photothermal conversion efficiency of 78% at a concentration of 434 µg mL−1. They can also carry doxorubicin (DOX) and rapidly release it upon NIR irradiation. Additionally, preliminary results regarding the biocompatibility of these micromotors through in vitro tests on a 3D breast cancer model demonstrate low cytotoxicity and strong accumulation. These promising results suggest that such Fe-rGO core–shell micromotors could hold great potential for combined photothermal therapy