Clinacanthus nutans crude polysaccharide extract as a green platform for microwave-assisted synthesis of silver nanoparticles: Optimization, characterization, and evaluation of bioactivities.

Clinacanthus nutans (C. nutans) is a plant in tropical Asia with proven biological activities. The optimized extraction method of C. nutans crude polysaccharide (CNP) uses water in the presence of an ultrasound-assisted mechanical method (UL_CNP). However, the use of UL_CNP for the synthesis and optimization of silver nanoparticles (AgNP), particularly their anticancer and photocatalytic properties, remains unexplored. Hence, this research aimed to employ a green method using UL_CNP and silver nitrate to produce AgNP (UL_AgNP) with a small size and assess its potential toxicity, anticancer, and photocatalytic activities. The synthesis condition was optimized using the Box-Behnken design method. The synthesized UL_AgNP showed the surface plasmon resonance peak at 458 nm. The optimized synthesis condition produced spherically shaped UL_AgNP with a size of 5.21 ± 1.92 nm and a zeta potential of -26.33 ± 0.93 mV. An X-ray diffraction analysis exhibited intense Bragg's reflection peaks at (111), (200), (220), and (311), having a face-centered cubic structure of AgNP. Attenuated total reflectance-Fourier-transform infrared spectroscopy and energy-dispersive X-ray spectroscopy further confirmed the presence of silver in the synthesized UL_AgNP. The brine shrimp lethality test of UL_AgNP reported a lethal concentration 50 value of <7.8 µg/mL after 24 h. The UL_AgNP exhibited antiproliferative activity against MCF-7 cells with a half-maximal inhibitory concentration value of 4.96 ± 0.31 µg/mL by inducing S-phase cell cycle arrest, apoptotic effect, and reduction of cell migration. Furthermore, UL_AgNP proved its efficient photocatalytic activity against methylene blue dye (50.22 % ± 0.06 %, after 10 min at a concentration of 50 µg/mL). Therefore, the UL_AgNP exhibited promising antiproliferative activity against MCF-7 cells, highlighting their potential as a therapeutic agent. Further investigations are needed to elucidate the precise mechanism of their action.

Phytofabrication and Characterisation of Zinc Oxide Nanoparticles Using Pure Curcumin.

Zinc oxide and curcumin, on their own and in combination, have the potential as alternatives to conventional anticancer drugs. In this work, zinc oxide nanoparticles (ZnO NPs) were prepared by an eco-friendly method using pure curcumin, and their physicochemical properties were characterised. ATR-FTIR spectra confirmed the role of curcumin in synthesising zinc oxide curcumin nanoparticles (Green-ZnO-NPs). These nanoparticles exhibited a hexagonal wurtzite structure with a size and zeta potential of 27.61 ± 5.18 nm and -16.90 ± 0.26 mV, respectively. Green-ZnO-NPs showed good activity towards studied bacterial strains, including Escherichia coli, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. The minimum inhibitory concentration of Green-ZnO-NPs was consistently larger than that of chemically synthesised ZnO NPs (Std-ZnO-NPs) or mere curcumin, advocating an additive effect between the zinc oxide and curcumin. Green-ZnO-NPs demonstrated an efficient inhibitory effect towards MCF-7 cells with IC50 (20.53 ± 5.12 µg/mL) that was significantly lower compared to that of Std-ZnO-NPs (27.08 ± 0.91 µg/mL) after 48 h of treatment. When Green-ZnO-NPs were tested against Artemia larvae, a minimised cytotoxic effect was observed, with LC50 being almost three times lower compared to that of Std-ZnO-NPs (11.96 ± 1.89 µg/mL and 34.60 ± 9.45 µg/mL, respectively). This demonstrates that Green-ZnO-NPs can be a potent, additively enhanced combination delivery/therapeutic agent with the potential for anticancer therapy.

Advanced Drug Delivery Systems for Renal Disorders.

Kidney disease management and treatment are currently causing a substantial global burden. The kidneys are the most important organs in the human urinary system, selectively filtering blood and metabolic waste into urine via the renal glomerulus. Based on charge and/or molecule size, the glomerular filtration apparatus acts as a barrier to therapeutic substances. Therefore, drug distribution to the kidneys is challenging, resulting in therapy failure in a variety of renal illnesses. Hence, different approaches to improve drug delivery across the glomerulus filtration barrier are being investigated. Nanotechnology in medicine has the potential to have a significant impact on human health, from illness prevention to diagnosis and treatment. Nanomaterials with various physicochemical properties, including size, charge, surface and shape, with unique biological attributes, such as low cytotoxicity, high cellular internalization and controllable biodistribution and pharmacokinetics, have demonstrated promising potential in renal therapy. Different types of nanosystems have been employed to deliver drugs to the kidneys. This review highlights the features of the nanomaterials, including the nanoparticles and corresponding hydrogels, in overcoming various barriers of drug delivery to the kidneys. The most common delivery sites and strategies of kidney-targeted drug delivery systems are also discussed.

Synthesis of Zinc Oxide Nanoparticles with Bioflavonoid Rutin: Characterisation, Antioxidant and Antimicrobial Activities and In Vivo Cytotoxic Effects on Artemia Nauplii.

This study aims to synthesise zinc oxide nanoparticles with rutin (ZnO-R NPs) using a green synthesis approach and characterise the nanostructures for diverse biomedical applications. In this study, the optical and chemical properties of synthesised ZnO-R NPs were verified through Fourier transform infrared (FTIR) spectroscopy and ultraviolet-visible (UV-Vis) spectroscopy. The FTIR spectroscopy revealed a symmetric bending vibration peak of 460 cm-1 for ZnO-R NPs, whereas UV-Vis spectroscopy showed a distinct absorption band at 395 nm. Moreover, the oval-shaped morphology of ZnO-R NPs was verified through scanning electron microscopy and transmission electron microscopy. The synthesised nanoformulation revealed a wurtzite structure with a crystallite size of 13.22 nm; however, the zeta potential value was recorded as -8.50 ± 0.46 mV for ZnO-R NPs. According to an antioxidant study, ZnO-R NPs demonstrated lower free-radical scavenging activity than pure rutin. The cytotoxicity study was conducted using a human breast cancer cell line (MCF-7). In vitro analysis verified that ZnO-R NPs exhibited significantly higher anticancer and microbial growth inhibition activities than standard ZnO NPs (ZnO Std NPs) and pure rutin. In addition, ZnO-R NPs revealed a significantly lower IC50 value than the commercial ZnO Std NPs and pure rutin in MCF-7 cells (16.39 ± 6.03 µg/mL, 27 ± 0.91 µg/mL and 350 ± 30.1 µg/mL, respectively) after 48 h. However, synthesised ZnO-R NPs demonstrated no significant toxicity towards Artemia nauplii. These results highlight the synthesis of rutin-mediated ZnO NPs and their possible chemotherapeutic potential.

Current Advances in Chitosan Nanoparticles Based Oral Drug Delivery for Colorectal Cancer Treatment.

As per the WHO, colorectal cancer (CRC) caused around 935,173 deaths worldwide in 2020 in both sexes and at all ages. The available anticancer therapies including chemotherapy, radiotherapy and anticancer drugs are all associated with limited therapeutic efficacy, adverse effects and low chances. This has urged to emerge several novel therapeutic agents as potential therapies for CRC including synthetic and natural materials. Orally administrable and targeted drug delivery systems are attractive strategies for CRC therapy as they minimize the side effects, enhance the efficacy of anticancer drugs. Nevertheless, oral drug delivery till today faces several challenges like poor drug solubility, stability, and permeability. Various oral nano-based approaches and targeted drug delivery systems have been developed recently, as a result of the ability of nanoparticles to control the release of the encapsulant, drug targeting and reduce the number of dosages administered. The unique physicochemical properties of chitosan polymer assist to overcome oral drug delivery barriers and target the colon tumour cells. Chitosan-based nanocarriers offered additional improvements by enhancing the stability, targeting and bioavailability of several anti-colorectal cancer agents. Modified chitosan derivatives also facilitated CRC targeting through strengthening the protection of encapsulant against acidic and enzyme degradation of gastrointestinal track (GIT). This review aims to provide an overview of CRC pathology, therapy and the barriers against oral drug delivery. It also emphasizes the role of nanotechnology in oral drug targeted delivery system and the growing interest towards chitosan and its derivatives. The present review summarizes the relevant works to date that have studied the potential applications of chitosan-based nanocarrier towards CRC treatment.

Exploring the Effect of Glycerol and Hydrochloric Acid on Mesoporous Silica Synthesis: Application in Insulin Loading.

Mesoporous silica (MPS), a carrier for active pharmaceutical ingredients, has a wide range of particle and pore morphology. A thorough understanding of ingredients used in MPS synthesis is an important prerequisite for optimizing its physicochemical characteristics. The present study aimed to evaluate the effect of glycerol and hydrochloric acid on the characteristics of synthesized MPS. Ordered MPS materials were synthesized using the pluronic P123 template and tetraethyl orthosilicate (TEOS) precursor. A three-level factorial design was employed to study the interaction between glycerol and hydrochloric acid. The optimized MPS particles were reasonably uniform in shape (short and rod-shaped) and < 1 µm in size with a smooth surface morphology. The nitrogen adsorption-desorption analysis revealed that the uniform cylindrical pores of the prepared MPS had a diameter > 5 nm and a total surface area > 500 m2/g. With increasing acid and glycerol concentrations, the particle size of MPS decreased. However, while the glycerol increased the heterogeneity of the synthesized particles, the acid decreased it. The developed MPS was successfully loaded with a biological drug (insulin) with a 21.94% encapsulation efficiency. The MPS prepared in this study exhibits potential applications as a drug delivery carrier for drugs with a large molecular weight.

Biocompatible Supramolecular Mesoporous Silica Nanoparticles as the Next-Generation Drug Delivery System.

Supramolecular mesoporous silica nanoparticles (MSNs) offer distinct properties as opposed to micron-sized silica particles in terms of their crystal structure, morphology-porosity, toxicity, biological effects, and others. MSN biocompatibility has touched the pharmaceutical realm to exploit its robust synthesis pathway for delivery of various therapeutic molecules including macromolecules and small-molecule drugs. This article provides a brief review of MSN history followed by special emphasis on the influencing factors affecting morphology-porosity characteristics. Its applications as the next-generation drug delivery system (NGDDS) particularly in a controlled release dosage form via an oral drug delivery system are also presented and shall be highlighted as oral delivery is the most convenient route of drug administration with the economical cost of development through to scale-up for clinical trials and market launch.

Synthesis and Characterization of Novel Ternary-Hybrid Nanoparticles as Thermal Additives.

The performance of water as a heat transfer medium in numerous applications is limited by its effective thermal conductivity. To improve the thermal conductivity of water, herein, we report the development and thermophysical characterization of novel metal-metal-oxide-carbon-based ternary-hybrid nanoparticles (THNp) GO-TiO2-Ag and rGO-TiO2-Ag. The results indicate that the graphene oxide- and reduced graphene oxide-based ternary-hybrid nanoparticles dispersed in water enhance the base fluid (H2O) thermal conductivity by 66% and 83%, respectively, even at very low concentrations. Mechanisms contributing to this significant enhancement are discussed. The experimental thermal conductivity is plotted against the existing empirical hybrid thermal conductivity correlations. We found that those correlations are not suitable for the metal-metal-oxide-carbon combinations, calling for new thermal conductivity models. Furthermore, the rheological measurements of the nanofluids display non-Newtonian behavior, and the viscosity reduces with the increase in temperature. Such behavior is possibly due to the non-uniform shapes of the ternary-hybrid nanoparticles.

3D culture of cancer cells in alginate hydrogel beads as an effective technique for emergency cell storage and transportation in the pandemic era.

Due to the restrictions in accessing research laboratories and the challenges in providing proper storage and transportation of cells during the COVID-19 pandemic, having an effective and feasible mean to solve these challenges would be of immense help. Therefore, we developed a 3D culture setting of cancer cells using alginate beads and tested its effectiveness in different storage and transportation conditions. The viability and proliferation of cancer cells were assessed using trypan blue staining and quantitative CCK-8 kit, respectively. The developed beads allowed cancer cells survival up to 4 weeks with less frequent maintenance measures such as change of the culture media or subculture of cells. In addition, the recovery of cancer cells and proliferation pattern were significantly faster with better outcomes in the developed 3D alginate beads compared to the standard cryopreservation of cells or the 2D culture conditions. The 3D alginate beads also supported the viability of cells while the shipment at room temperature for a duration of up to 5 days with no humidity or CO2  support. Therefore, 3D culture in alginate beads can be used to store or ship biological cells with ease at room temperature with minimal preparations.

Electrosprayed Alginate Nanoparticles as CRISPR Plasmid DNA Delivery Carrier: Preparation, Optimization, and Characterization.

Therapeutic gene editing is becoming more feasible with the emergence of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) system. However, the successful implementation of CRISPR/Cas9-based therapeutics requires a safe and efficient in vivo delivery of the CRISPR components, which remains challenging. This study presents successful preparation, optimization, and characterization of alginate nanoparticles (ALG NPs), loaded with two CRISPR plasmids, using electrospray technique. The aim of this delivery system is to edit a target gene in another plasmid (green fluorescent protein (GFP)). The effect of formulation and process variables were evaluated. CRISPR ALG NPs showed mean size and zeta potential of 228 nm and -4.42 mV, respectively. Over 99.0% encapsulation efficiency was achieved while preserving payload integrity. The presence of CRISPR plasmids in the ALG NPs was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy. The tests revealed that the nanoparticles were cytocompatible and successfully introduced the Cas9 transgene in HepG2 cells. Nanoparticles-transfected HepG2 was able to edit its target plasmid by introducing double-strand break (DSB) in GFP gene, indicating the bioactivity of CRISPR plasmids encapsulated in alginate nanoparticles. This suggests that this method is suitable for biomedical application in vitro or ex vivo. Future investigation of theses nanoparticles might result in nanocarrier suitable for in vivo delivery of CRISPR/Cas9 system.