Insight into Preventing Global Dengue Spread: Nanoengineered Niclosamide for Viral Infections.

Millions of cases of dengue virus (DENV) infection yearly from Aedes mosquitoes stress the need for effective antivirals. No current drug effectively combats dengue efficiently. Transient immunity and severe risks highlight the need for broad-spectrum antivirals targeting all serotypes of DENV. Niclosamide, an antiparasitic, shows promising antiviral activity against the dengue virus, but enhancing its bioavailability is challenging. To overcome this issue and enable niclosamide to address the global dengue problem, nanoengineered niclosamides can be the solution. Not only does it address cost issues but also with its broad-spectrum antiviral effects nanoengineered niclosamide offers hope in addressing the current health crisis associated with DENV and will play a crucial role in combating other arboviruses as well.

The Next Generation COVID-19 Antiviral; Niclosamide-Based Inorganic Nanohybrid System Kills SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic is a serious global threat with surging new variants of concern. Although global vaccinations have slowed the pandemic, their longevity is still unknown. Therefore, new orally administrable antiviral agents are highly demanded. Among various repurposed drugs, niclosamide (NIC) is the most potential one for various viral diseases such as COVID-19, SARS (severe acute respiratory syndrome), MERS (middle east respiratory syndrome), influenza, RSV (respiratory syncytial virus), etc. Since NIC cannot be effectively absorbed, a required plasma concentration for antiviral potency is hard to maintain, thereby restricting its entry into the infected cells. Such a 60-year-old bioavailability challenging issue has been overcome by engineering with MgO and hydroxypropyl methylcellulose (HPMC), forming hydrophilic NIC-MgO-HPMC, with improved intestinal permeability without altering NIC metabolism as confirmed by parallel artificial membrane permeability assay. The inhibitory effect on SARS-CoV-2  replication is confirmed in the Syrian hamster model to reduce lung injury. Clinical studies reveal that the bioavailability of NIC hybrid drug can go 4 times higher than the intact NIC. The phase II clinical trial shows a dose-dependent bioavailability of NIC from hybrid drug  suggesting its potential applicability as a game changer in achieving the much-anticipated endemic phase.

Implantable multireservoir device with stimulus-responsive membrane for on-demand and pulsatile delivery of growth hormone.

Implantable devices for on-demand and pulsatile drug delivery have attracted considerable attention; however, many devices in clinical use are embedded with the electronic units and battery inside, hence making them large and heavy for implantation. Therefore, we propose an implantable device with multiple drug reservoirs capped with a stimulus-responsive membrane (SRM) for on-demand and pulsatile drug delivery. The SRM is made of thermosensitive POSS(MEO2MA-co-OEGMA) and photothermal nanoparticles of reduced graphene oxide (rGO), and each of the drug reservoirs is filled with the same amount of human growth hormone (hGH). Therefore, with noninvasive near-infrared (NIR) irradiation from the outside skin, the rGO nanoparticles generate heat to rupture the SRM in the implanted device, which can open a single selected drug reservoir to release hGH. Therefore, the device herein is shown to release hGH reproducibly only at the times of NIR irradiation without drug leakage during no irradiation. When implanted in rats with growth hormone deficiency and irradiated with an NIR light from the outside skin, the device exhibits profiles of hGH and IGF1 plasma concentrations, as well as body weight change, similar to those in animals treated with conventional s.c. hGH injections.

The emergence of nanoporous materials in lung cancer therapy.

Lung cancer is one of the most common cancers, affecting more than 2.1 million people across the globe every year. A very high occurrence and mortality rate of lung cancer have prompted active research in this area with both conventional and novel forms of therapies including the use of nanomaterials based drug delivery agents. Specifically, the unique physico-chemical and biological properties of porous nanomaterials have gained significant momentum as drug delivery agents for delivering a combination of drugs or merging diagnosis with targeted therapy for cancer treatment. This review focuses on the emergence of nano-porous materials for drug delivery in lung cancer. The review analyses the currently used nanoporous materials, including inorganic, organic and hybrid porous materials for delivering drugs for various types of therapies, including chemo, radio and phototherapy. It also analyses the selected research on stimuli-responsive nanoporous materials for drug delivery in lung cancer before summarizing the various findings and projecting the future of emerging trends. This review provides a strong foundation for the current status of the research on nanoporous materials, their limitations and the potential for improving their design to overcome the unique challenges of delivering drugs for the treatment of lung cancer.

Bio-Inorganic Layered Double Hydroxide Nanohybrids in Photochemotherapy: A Mini Review.

Clay-based bio-inorganic nanohybrids, such as layered double hydroxides (LDH), have been extensively researched in the various fields of biomedicine, particularly for drug delivery and bio-imaging applications. Recent trends indicate that such two-dimensional LDH can be hybridized with a variety of photo-active biomolecules to selectively achieve anti-cancer benefits through numerous photo/chemotherapies (PCT), including photothermal therapy, photodynamic therapy, and magnetic hyperthermia, a combination of therapies to achieve the best treatment regimen for patients that cannot be treated either by surgery or radiation alone. Among the novel two-dimensional clay-based bio-inorganic nanohybrids, LDH could enhance the photo-stability and drug release controllability of the PCT agents, which would, in turn, improve the overall phototherapeutic performance. This review article highlights the most recent advances in LDH-based two-dimensional clay-bio-inorganic nanohybrids for the aforementioned applications.

Polyphosphazene-Based Biomaterials for Biomedical Applications.

Recently, synthetic polymers have attracted great interest in the field of biomedical science. Among these, polyphosphazenes (PPZs) are regarded as one of the most promising materials, due to their structural flexibility and biodegradability compared to other materials. PPZs have been developed through numerous studies. In particular, multi-functionalized PPZs have been proven to be potential biomaterials in various forms, such as nanoparticles (NPs) and hydrogels, through the introduction of various functional groups. Thus, PPZs have been applied for the delivery of therapeutic molecules (low molecular weight drugs, genes and proteins), bioimaging, phototherapy, bone regeneration, dental liners, modifiers and medical devices. The main goal of the present review is to highlight the recent and the most notable existing PPZ-based biomaterials for aforementioned applications, with future perspectives in mind.

pH-Responsive Inorganic/Organic Nanohybrids System for Controlled Nicotinic Acid Drug Release.

Although nicotinic acid (NA) has several clinical benefits, its potency cannot be fully utilized due to several undesirable side effects, including cutaneous flushing, GIT-associated symptoms, etc. To overcome such issues and improve the NA efficacy, a new inorganic-organic nanohybrids system was rationally designed. For making such a hybrid system, NA was intercalated into LDH through a coprecipitation technique and then coated with Eudragit® S100 to make the final drug delivery system called Eudragit® S100-coated NA-LDH. The as-made drug delivery system not only improved the NA release profile but also exhibited good bio-compatibility as tested on L929 cells. Such an inorganic-organic nanohybrid drug delivery agent is expected to reduce the undesirable side effects associated with NA and hopefully improve the pharmacological effects without inducing any undesirable toxicity.

Niclosamide encapsulated in mesoporous silica and geopolymer: A potential oral formulation for COVID-19.

COVID-19 is a rapidly evolving emergency, for which there have been no specific medication found yet. Therefore, it is necessary to find a solution for this ongoing pandemic with the aid of advanced pharmaceutics. What is proposed as a solution is the repurposing of FDA approved drug such as niclosamide (NIC) having multiple pathways to inactivate the SARS-CoV-2, the specific virion that induces COVID-19. However, NIC is hardly soluble in an aqueous solution, thereby poor bioavailability, resulting in low drug efficacy. To overcome such a disadvantage, we propose here an oral formulation based on Tween 60 coated drug delivery system comprised of three different mesoporous silica biomaterials like MCM-41, SBA-15, and geopolymer encapsulated with NIC molecules. According to the release studies under a gastro/intestinal solution, the cumulative NIC release out of NIC-silica nanohybrids was found to be greatly enhanced to ~97% compared to the solubility of intact NIC (~40%) under the same condition. We also confirmed the therapeutically relevant bioavailability for NIC by performing pharmacokinetic (PK) study in rats with NIC-silica oral formulations. In addition, we discussed in detail how the PK parameters could be altered not only by the engineered porous structure and property, but also by interfacial interactions between ion-NIC dipole, NIC-NIC dipoles and/or pore wall-NIC van der Waals in the intra-pores of silica nanoparticles.

Doxorubicin Encapsulated in TPGS-Modified 2D-Nanodisks Overcomes Multidrug Resistance.

Multidrug resistance (MDR) is regarded as a main obstacle for effective chemotherapy, and P-glycoprotein (P-gp)-mediated drug efflux has been demonstrated to be the key factor responsible for MDR. In this study, a novel pH-responsive hybrid drug delivery system was developed by conjugating d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a kind of P-gp inhibitor, on the surface of laponite nanodisks to overcome MDR. The prepared LM-TPGS display excellent colloidal stability, a high encapsulation efficiency of doxorubicin (DOX), and a pH-responsive drug release profile. In vitro experiments verified that LM-TPGS/DOX could exhibit significantly enhanced therapeutic efficacy in treating DOX-resistant breast cancer cells (MCF-7/ADR) through inhibiting the activity of P-gp-mediated drug efflux and effectively accumulating DOX within cancer cells. In vivo results revealed that LM-TPGS/DOX outstandingly suppressed MCF-7/ADR tumors with low side effects. Therefore, the high drug payload, enhanced inhibition efficacy to drug-resistant cells, and low side effects make the LM-TPGS/DOX a promising nanoplatform to reverse MDR for effective chemotherapy.

Alendronate-Anionic Clay Nanohybrid for Enhanced Osteogenic Proliferation and Differentiation.

BACKGROUND: Alendronate (AL), a drug for inhibiting osteoclast-mediated bone-resorption, was intercalated into an inorganic drug delivery nanovehicle, layered double hydroxide (LDH), to form a new nanohybrid, AL-LDH, with 1:1 heterostructure along the crystallographic C-axis. Based on the intercalation reaction strategy, the present AL-LDH drug delivery system (DDS) was realized with an enhanced drug efficacy of AL, which was confirmed by the improved proliferation and osteogenic differentiation of osteoblast-like cells (MG63). METHODS: The AL-LDH nanohybrid was synthesized by conventional ion-exchange reaction and characterized by powder X-ray diffraction (PXRD), high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared (FT-IR) spectroscopy. Additionally, in vitro efficacy tests, such as cell proliferation and alkaline phosphatase (ALP) activity, were analyzed. RESULTS: The AL was successfully intercalated into LDH via ion-exchange reaction, and thus prepared AL-LDH DDS was X-ray single phasic and chemically well defined. The accumulated AL content in MG63 cells treated with the AL-LDH DDS nanoparticles was determined to be 10.6-fold higher than that within those treated with the intact AL after incubation for 1 hour, suggesting that intercellular permeation of AL was facilitated thanks to the hybridization with drug delivery vehicle, LDH. Furthermore, both in vitro proliferation level and ALP activity of MG63 treated with the present hybrid drug, AL-LDH, were found to be much more enhanced than those treated with the intact AL. This is surely due to the fact that LDH could deliver AL drug very efficiently, although LDH itself does not show any effect on proliferation and osteogenic differentiation of MG63 cells. CONCLUSION: The present AL-LDH could be considered as a promising DDS for improving efficacy of AL.

2D Nanostructured Metal Hydroxides with Gene Delivery and Theranostic Functions; A Comprehensive Review.

Layered double hydroxides (LDHs) with two dimensional structure have been attracted considerable interest in exploring new intercalative nanohybrids, such as inorganic-LDHs, organic-LDHs and bio-LDHs ones, which often exhibit extraordinarily synergetic effects and complementary performances. More recently, bio-related nanotechnology becomes one of the most essential research field in the viewpoint of the health and safety of human being. In this regard, LDHs have been focused as an important inorganic material for gene and drug delivery carriers with imaging and targeting functions. In the present review, an attempt has been made to describe gene delivery systems based on LDH nanoparticles in terms of synthetic routes of gene-LDH nanohybrids, their physico-chemical properties, intercellular uptake mechanisms, intracellular trafficking pathways and drug resistance, and passive and active targeting functions in in-vitro and in-vivo, and finally imaging functions. And recent studies of gene-therapies with LDHs are also discussed from the viewpoint of state-of-the-art nanohybrids technology.

Polylactic Acid/Chitosan Nanoparticles Loading Nifedipine: Characterization Findings and In Vivo Investigation in Animal.

This paper presents the results of zeta potential, water contact angle, atomic force microscopy image, in vitro solubility, and content of heavy metals in polylactic acid (PLA)/chitosan (CS) nanoparticles loading nifedipine. In addition, the In Vivo test of the PLA/CS nanoparticles loading nifedipine in the mice is also one of highlights of this work. The Zeta potential result shows that the charged surface of the PLA/CS nanoparticles loading nifedipine is neutral, negative or complex depending on nifedipine content. Nifedipine plays a role in increase of hydrophobic property, swelling degree and regular surface as well as decrease of surface rough of the nanoparticles. The PLA/CS/nifedipine nanoparticles are dissolved in the solutions with pH 6.8, pH 4.5 and pH 1.2. The In Vivo test of PLA/CS nanoparticles loading nifedipine on mice was evaluated by the change in diastolic pressure, systolic pressure, arterial pressure and heart rate. The obtained results confirm that the PLA/CS nanoparticles loading nifedipine is suitable to apply in the treatment of hypertension patients lately.

Correction: Mesoporous carbon nitrides: synthesis, functionalization, and applications.

Correction for 'Mesoporous carbon nitrides: synthesis, functionalization, and applications' by Kripal S. Lakhi et al., Chem. Soc. Rev., 2017, DOI: .

Mesoporous carbon nitrides: synthesis, functionalization, and applications.

Mesoporous carbon nitrides (MCNs) with large surface areas and uniform pore diameters are unique semiconducting materials and exhibit highly versatile structural and excellent physicochemical properties, which promote their application in diverse fields such as metal free catalysis, photocatalytic water splitting, energy storage and conversion, gas adsorption, separation, and even sensing. These fascinating MCN materials can be obtained through the polymerization of different aromatic and/or aliphatic carbons and high nitrogen containing molecular precursors via hard and/or soft templating approaches. One of the unique characteristics of these materials is that they exhibit both semiconducting and basic properties, which make them excellent platforms for the photoelectrochemical conversion and sensing of molecules such as CO2, and the selective sensing of toxic organic acids. The semiconducting features of these materials are finely controlled by varying the nitrogen content or local electronic structure of the MCNs. The incorporation of different functionalities including metal nanoparticles or organic molecules is further achieved in various ways to develop new electronic, semiconducting, catalytic, and energy harvesting materials. Dual functionalities including acidic and basic groups are also introduced in the wall structure of MCNs through simple UV-light irradiation, which offers enzyme-like properties in a single MCN system. In this review article, we summarize and highlight the existing literature covering every aspect of MCNs including their templating synthesis, modification and functionalization, and potential applications of these MCN materials with an overview of the key and relevant results. A special emphasis is given on the catalytic applications of MCNs including hydrogenation, oxidation, photocatalysis, and CO2 activation.

Biodegradable Inorganic Nanovector: Passive versus Active Tumor Targeting in siRNA Transportation.

The biodegradable inorganic nanovector based on a layered double hydroxide (LDH) holds great promise for gene and drug delivery systems. However, in vivo targeted delivery of genes through LDH still remains a key challenge in the development of RNA interference therapeutics. Here, we describe in vivo and in vitro delivery system for Survivin siRNA (siSurvivin) assembled with passive LDH with a particle size of 100 nm or active LDH conjugated with a cancer overexpressing receptor targeting ligand, folic acid (LDHFA), conferring them an ability to target the tumor by either EPR-based clathrin-mediated or folate receptor-mediated endocytosis. When not only transfected into KB cells but also injected into xenograft mice, LDHFA/siSurvivin induced potent gene silencing at mRNA and protein levels in vitro, and consequently achieved a 3.0-fold higher suppression of tumor volume than LDH/siSurvivin in vivo. This anti-tumor effect was attributed to a selectively 1.2-fold higher accumulation of siSurvivin in tumor tissue compared with other organs. Targeting to the tumor with inorganic nanovector can guide and accelerate an evolution of next-generation theranosis system.

Highly ordered nanoporous carbon films with tunable pore diameters and their excellent sensing properties.

Ordered porous carbon films with tunable pore diameters, immobilized with glucose oxidase (GOD) have been fabricated and employed for the construction of a biosensor for glucose molecules. The as-prepared porous films have large specific surface areas and highly ordered porous structure with uniform pore sizes, which are critical for the immobilization of large amounts of GOD and support the promotion of heterogeneous electron transfer. The developed biosensors give enough room for the encapsulation of a high amount of GOD molecules and show excellent biosensing performance with a linear response to glucose concentration ranging from 0.5 to 9 mM and a detection limit of 1.5 µM. It is also demonstrated that the sensitivity of the biosensor can be easily tuned by modulating the pore size of carbon film as it dictates the amount of immobilization of GOD in the porous channels. The fabricated carbon-film-based biosensor has a good stability and a high reproducibility, which opens the gateway for the commercialization of this excellent technology.

Highly magnetic nanoporous carbon/iron-oxide hybrid materials.

The preparation of size-controllable Fe2O3 nanoparticles grown in nanoporous carbon with tuneable pore diameters is reported. These hybrid materials exhibit strong non-linear magnetic properties and a magnetic moment of approximately 229 emu g(-1), which is the highest value ever reported for nanoporous hybrids, and can be attributed to the nanosieve effect and the strong interaction between the nanoparticles and the carbon walls.

Mesoporous BN and BCN nanocages with high surface area and spherical morphology.

Novel mesoporous BN and BCN materials with cage type porous structure and spherical morphology have been synthesized using carbon nanocages with 3D porous structure as a template via an elemental substitution method at a low synthesis temperature. The obtained materials exhibit a large specific pore volume with uniform pore size distribution and the specific surface area ranging from 945 to 1023 m(2) g(-1).

A functionalized cell membrane biomimetic nanoformulation based on layered double hydroxide for combined tumor chemotherapy and sonodynamic therapy.

The development of nanoformulations with simple compositions that can exert targeted combination therapy still remains a great challenge in the area of precision cancer nanomedicine. Herein, we report the design of a multifunctional nanoplatform based on methotrexate (MTX)-loaded layered double hydroxide (LDH) coated with chlorin e6 (Ce6)-modified MCF-7 cell membranes (CMM) for combined chemo/sonodynamic therapy of breast cancer. LDH nanoparticles were in situ loaded with MTX via coprecipitation, and coated with CMM that were finally functionalized with phospholipid-modified Ce6. The created nanoformulation of LDH-MTX@CMM-Ce6 displays good colloidal stability under physiological conditions and can release MTX in a pH-dependent manner. We show that the formulation can homologously target breast cancer cells, and induce their significant apoptosis through arresting the cell cycle via cooperative MTX-based chemotherapy and ultrasound (US)-activated sonodynamic therapy. The assistance of US can not only trigger sonosensitizer Ce6 to produce reactive oxygen species, but also enhance the cellular uptake of LDH-MTX@CMM-Ce6 via an acoustic cavitation effect. Upon intravenous injection and US irradiation, LDH-MTX@CMM-Ce6 displays an admirable antitumor performance towards a xenografted breast tumor mouse model. Furthermore, the modification of Ce6 on the CMM endows the LDH-based nanoplatform with fluorescence imaging capability. The developed LDH-based nanoformulation here provides a general intelligent cancer nanomedicine platform with simple composition and homologous targeting specificity for combined chemo/sonodynamic therapy and fluorescence imaging of tumors.

Aripiprazole-montmorillonite: a new organic-inorganic nanohybrid material for biomedical applications.

Poor aqueous solubility and the unpleasant taste of aripiprazole (APZ) have been recurring problems, owing to its low bioavailability and low patient tolerance, respectively. Herein, we prepared a nanohybrid system that was based on a bentonite clay material, montmorillonite (MMT), which could both mask the taste and enhance the solubility of APZ (i.e., APZ-MMT). To further improve the efficacy of this taste masking and drug solubility, APZ-MMT was also coated with a cationic polymer, polyvinylacetal diethylamino acetate (AEA). In vitro dissolution tests at neutral pH showed that the amount of drug that was released from the AEA-coated APZ-MMT was greatly suppressed (<1%) for the first 3 min, thus suggesting that AEA-coated APZ-MMT has strong potential for the taste masking of APZ. Notably, in simulated gastric juice at pH 1.2, the total percentage of APZ that was released within the first 2 h increased up to 95% for AEA-coated APZ-MMT. Furthermore, this in vitro release profile was also similar to that of Abilify®, a commercially available medication. In vivo experiments by using Sprague-Dawley rats were also performed to compare the pharmacokinetics of AEA-coated APZ-MMT and Abilify®. AEA-coated APZ-MMT exhibited about 20% higher systemic exposure of APZ and its metabolite, dehydro-APZ, compared with Abilify®. Therefore, a new MMT-based nanovehicle, which is coated with a cationic polymer, can act as a promising delivery system for both taste masking and for enhancing the bioavailability of APZ.