Nanoscience & Nanotechnology-Asia - Volume 11, Issue 1, 2021

Cancer is a leading cause of mortality, and its individual and collective impact is substantial. Conventional chemotherapy utilizes drugs that effectively destroy tumour cells. However, these agents destroy healthy cells along with the tumour cells, leading to many adverse effects, which include hypersensitivity reactions, nephrotoxicity, and neurotoxicity. To minimize these adverse effects, various drug delivery systems (DDSs) have been developed. Among them, nano drug delivery systems are particularly attractive platform. Thus, this review paper explores recent work on targeted delivery; tumour accumulation enhancement and sustained blood circulation using more effective biomaterials to enhance the properties of nanoparticles. Moreover, various target-specific drug delivery mechanisms, such as antibody-mediated delivery as well as the targeting of angiogenesis, mitochondria, and the CD44 receptor, are also explained.

To study an in-depth overview of tumor microenvironment, its target sites and the impact of nanoformulation in the modulation of tumor microenvironment specifically in the case of breast cancer as a treatment strategy. Tumor microenvironment has many sites for possible action such as extracellular matrix, acidic pH, vascular abnormalities, etc. Nanoformulation may change tumor microenvironment via targeting these sites and help to treat cancer. Various types of cancer were treated through this mechanism and discussed in this manuscript. In the future, discussed mechanisms may play a pivotal role to develop new nano-drug delivery for cancer therapy. It can be concluded after extensive literature survey that nanoformulation is able to modulate tumor microenvironment specifically in case of breast cancer which leads to beneficial therapeutic effect against tumor growth. Improved understanding of this relation (nano-formulation and tumor microenvironment) may provide many ideas to develop new nanoformulation for breast cancer treatment.

Aim: To propose a method of KBT synthesis at a lower temperature to solve the volatility of the components. Background: Lead-based perovskite materials have long been employed in electroceramic industries due to their excellent piezoelectric, ferroelectric, and dielectric properties. The high toxicity of lead, however, leads to the replacement of the use of lead-based perovskite in devices with more environmentally friendly materials. KBT powders are traditionally prepared by solid-state reaction through the calcinations of K2CO3, Bi2O3 and TiO2 at high temperature. The high-temperature calcination process leads to serious particle agglomeration, grain growth and small surface area, which decrease the activity of the KBT powder. Instability of the KBT ceramic according to the high volatility of its component ions at elevated temperatures was the main concern for the application feasibility. Objective: This work was aimed to present the simplified method called “sol-hydrothermal” for the synthesis of KBT nanoparticles. Microstructure and phase evolution of the nanoparticles were investigated in detail. Methods: The sol-hydrothermal method was performed in potassium hydroxide (KOH) solution at 140-200°C for 2-24 h. Results: The result showed that increasing hydrothermal temperatures from 140°C to 200°C, the crystal structure was changed from pseudo-cubic to tetragonal. At 200°C, phase separation was observed. Suitable hydrothermal time was found to be between 6-12 h, above which phase separation was also observed. Increasing the KOH solution concentration from 10 to 12 or 15 and finally, 20 M gave rise to greater KBT peak intensity, suggesting a more complete crystallization process when the concentration was increased. Tetragonal KBT nanoparticles with c/a ratio of 1.0620 were obtained under the synthesis condition of 180°C for 12 h in 20 M KOH solution. Sinterability of the synthesized KBT nano-particles was further investigated by varying the sintering temperatures from 1000°C to 1080°C; the highest relative density of 97% was obtained in the sample sintered at 1050°C. However, at this sintering temperature and beyond, the sublimation of the K-containing component occurred as evident by the appearance of Bi2O3 and Bi4Ti3O12 phases. Conclusion: In summary, KBT nanoparticles have been successfully prepared by the simple solhydrothermal method in a basic solution at low temperatures. Synthesis temperature, time and KOH concentration were found to affect the powder characteristics greatly. Increasing synthesis temperature was found to affect the phase development while increasing synthesis time resulted in the development of crystallinity of the KBT powder obtained. Increasing KOH concentration from 10 M to 20 M gave rise to different particle growth and agglomeration degrees. The optimum synthesis conditions were at 180°C for 24 h in 10 M KOH solution. At this condition, KBT powder with a uniform particle size distribution and tetragonal structure could be obtained. The synthesis powder showed excellent sinterability. Sintering at only 1020°C for 2 h gave rise to fine grain ceramics with 95% relative density. However, as potassium was prone to sublime, increasing sintering temperature to 1050°C and beyond resulted in K-deficient phases. Sintering of the KBT should be done in K-saturating atmosphere to suppress this sublimation.

Background: Cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NP) are natural biogenic inorganic material that is used in drug delivery mainly as a bone-remodeling agent as well as a delivery agent for various therapeutics against bone diseases. Curcumin possesses a wide safety margin and yet puzzled with the problem of poor bioavailability due to insolubility. Propounding in vitro and in vivo studies on toxicity assessments of newly synthesized nanoparticles are ongoing to overcome some crucial challenges regarding their safety administration. Nanotoxicology has paved ways for concise test protocols to monitor sequential events with regards to possible toxicity of newly synthesized nanomaterials. The development of nanoparticle with no or less toxic effect has gained tremendous attention. Objective: This study aimed at evaluating the in vitro cytotoxic effect of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) and assessing its biocompatibility on normal cells using standard techniques of WST’s assay. Methods: Standard techniques of WST’s assay was used for the evaluation of the biocompatibility and cytotoxicity. Results: The result showed that CSCaCO3NP and Cur-CSCaCO3NP possess minimal toxicity and high biocompatibility on normal cells even at a higher dose of 500 μg/ml and 40 μg/ml, respectively. Conclusion: CSCaCO3NP can be termed an excellent non-toxic nanocarrier for curcumin delivery. Hence, curcumin loaded cockle shell derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) could further be assessed for various in vivo and in vitro therapeutic applications against various bone- related ailments.

Background: Ramipril, an antihypertensive drug exhibits 28% of oral bioavailability and is also excreted out quickly through the kidneys. Moreover, numerous side effects of Ramipril have been reported such as, hypotension (postural), increasing potassium level, and angioedema, when it is presented as an immediate dosage form. Hence, to conquer the side-effects associated with the drug and to increase its bioavailability, the present study was undertaken. Objective: The objective of the proposed approach was to design, develop and optimize Ramiprilloaded solid lipid nanoparticles. Methods: Solvent emulsification and evaporation method were employed to prepare Ramiprilloaded solid lipid nanoparticles containing stearic acid and phosphatidylcholine as a lipid and surfactant, respectively. The prepared formulations were studied for particle size analysis, % entrapment efficiency, Zeta Potential, SEM, X-ray diffraction study, FTIR, NMR spectroscopy, in vitro release study and stability study. Results: The obtained results were noted to be within the standard limits. No interaction between Ramipril and other excipients, was confirmed with the FT-IR study of the formulations. Particle size analysis confirmed that the size of the prepared formulations ranged between 200-350 nm. The percent entrapment efficiency was observed in the range of 70.61-91.60%. The result of entrapment and particle size of the nanoparticles from the R5 batch was adjudged. The designed formulation noted a 70.50% cumulative drug release within a period of 7 h. The designed batch showed a mean zeta potential of -29.4 mV, exhibiting good stability of the formulation. Conclusion: The developed formulation was found to be stable and it represents a promising system for the sustained and controlled delivery of Ramipril.

Background: The research work involves the development of PLGA biodegradable microspheres loaded with dexamethasone for intraocular delivery. Objective: The study aimed to design and evaluate long acting PLGA microspheres for ocular delivery of dexamethasone. Methods: The present formulation involves the development of long-acting dexamethasone loaded microspheres composed of a biodegradable controlled release polymer, Poly(D,L-lactide-coglycolide) (PLGA), for the treatment of posterior segment eye disorders intravitreally. PLGA with a monomer ratio of 50:50 of lactic acid to glycolic acid was used to achieve a drug release for up to 45 days. Quality by Design approach was utilized for designing the experiments. Single emulsion solvent evaporation technique along with high-pressure homogenization was used to facilitate the formation of microspheres. Results: Particle size evaluation, drug content and drug entrapment efficiency were determined for the microspheres. Particle size and morphology were observed using Field Emission Gun- Scanning Electron Microscopy (FEG-SEM) and microspheres were in the size range of 1-5 μm. Assessment of drug release was done using in vitro studies and trans retinal permeation was observed by ex vivo studies using goat retinal tissues. Conclusion: Considering the dire need for prolonged therapeutic effect on diseases of the posterior eye, an intravitreal long-acting formulation was designed. The use of biodegradable polymer with biocompatible degradation products was a rational approach to achieve this aim. The outcome of the present research shows that developed microspheres would provide a long-acting drug profile and reduce the frequency of administration thereby improving patient compliance.

Background: In recent years, the applications of nanoparticles have received a great attention due to their industrial and biomedical applications, while their beneficial effects suffer from controversial results at clinical stages. Objective: In the current study, cytotoxicity of cerium oxide (CeNP) nanoparticles (100 nm) were evaluated using mitochondria derived from wistar rat's liver. Methods: Isolated mitochondria from rat’s liver were divided into 7 groups including group 1 as control and group 2 to 7 as treatment group with different doses of CeNP (5, 10, 50, 100, 250 and 500 mg/ml, respectively), for 24, 48 and 72 h. After exposure, oxidative stress biomarkers such as total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), catalase activity (CAT) and mitochondrial viability, were determined in isolated rat liver mitochondria. Results: Results have shown that CeNPs increase TAC, TTG, CAT, LPO and viability of mitochondria in various exposure times and confirm antioxidant properties of CeNPs in mithocondria while mitochondria is a main source for the generation of reactive oxygen species (ROS). Conclusion: CeNPs trigger a wide range of biological responses that vary from cytotoxic to cytoprotective.

Objective: In this study, magnetic iron oxide nanoparticles were synthesized by cost effective and an easy co-precipitation method. Methods: The effects of reaction parameters such as the mole ratio of Fe²⁺/Fe³⁺ (1/1, 1/2 and 1/3) and the base type (NaOH and NH4OH) on the average hydrodynamic diameter, zeta potential, chemical and morphological structure and saturation magnetization values of magnetic iron oxide nanoparticles were systematically investigated. Results: Magnetic iron oxide nanoparticles synthesized at the mole ratio of 1/2 using NH4OH base gave better results in terms of particle size and particle shape, magnetization value. Conclusion: In order to prevent the formation of different phases in the co-precipitation method, an alternative approach was developed and the reaction was performed using inert supercritical CO2 atmosphere.

Background and Objective: Biogenic nanomaterials are recently being researched in biomedicine for their antioxidant, antimicrobial, anti-inflammatory and antitumor performance. In this study, gold nanoparticles (AuNPs) were biologically synthesized using Nothapodytes foetida (N. foetida), a camptothecin producing plant, to evaluate its potent cytotoxic activity against cancer cells and antimicrobial activities against human pathogenic bacteria. Methods: The AuNPs were characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and dynamic light scattering (DLS). The antimicrobial activity of AuNPs was determined by conducting the minimum inhibitory concentration (MIC) assay on gram positive and gram negative bacteria, whereas cytotoxicity against cancer cells was assessed through the MTT assay and genotoxicity was assayed by DNA fragmentation. Results: TEM and DLS results showed the synthesis of 20-200 nm sized M. foetida AuNPs (NFAuNPs). The NFAuNPs exerted growth inhibitory effects on gram negative bacteria with the MIC for the inhibition of Eschericia coli, Pseudomonas aeruginosa being 0.15 mg/mL and 0.25 mg/mL respectively. The cytotoxicity results indicated that the sublethal concentrations of NFAuNPs for inhibiting 50% of cell growth (IC50) of cancer cells including HeLa, MCF-7 and HCT-15 after 48 h of exposure were 7.2, 9.67 and 5.28 μg/mL respectively. DNA fragmentation in cells exposed to 10-75 μg/mL of NFAuNP concentrations revealed their genotoxic effects. Conclusion: The study revealed the biogenic synthesis of AuNPs using the N. foetida plant extract and its biological potential as an antimicrobial and anticancer agent.

Introduction: Here, we present an n-channel cylindrical gate tunnel FET with drain underlap engineering (CGT-DU) and the simulation process is carried out using a 3-D device simulator from Synopsys. Methods: The analog and radio frequency (RF) performance of the device has been studied extensively in terms of the electric field, energy band analysis, drain current, gain bandwidth product, unity gain cutoff frequency, transconductance frequency product, and maximum oscillation frequency for different values of drain underlap length. Results: The increase in underlap length in CGT paves the way for a substantial reduction in ambipolar current without degrading the ON-state current. The proposed device exhibits lower lateral electric field, larger tunneling length and lower gate to drain capacitance at the drain end with a higher underlap length. Conclusion: CGT-DU exhibits superior ambipolar and RF performance without degrading ONstate current and threshold voltage.

Background: The current research work reports an investigation of the effects of employing CuO and TiO² nanoparticles as potential additives to refinery (petroleum) diesel fuel, in order to reduce the emissions of combustion process as well as to enhance the combustion process. Methods: Nanodiesel samples were prepared with various concentrations (50 ppm, 100 ppm, 200 ppm, 300 ppm). The experimental work was conducted using a four stroke diesel engine with a single cylinder at various loads in order to accurately determine the influence of nanoparticles on combustion process. The experimental readings were measured at two conditions, cold start and hot start relative to the engine. Results: It was clearly observed that the nanodiesel fuels have significantly reduced CO, CO², NO, unburned HC, and enhanced the engine performance. According to the experimental results the 100 ppm TiO² and 200 ppm CuO nanodiesel have showed almost the highest performance and lowest emissions comparable to neat diesel fuel and other nanodiesel samples. Owing to 100 ppm TiO2 on hot start conditions, it was found that the CO, CO², NO, unburnt HC, exhaust temperature, and BSFC have been reduced by 41.4%, 37 %, 38.3%, 81%, 4.9%, and 20.5% respectively at maximum load. Meanwhile, the brake power, RPM and thermal efficiency have increased by 1.5%, 1% and 2.65% respectively. Conclusion: Eventually the stability of nanodiesel fuels were investigated. Accordingly, the stability of 100 ppm TiO² and for 200 ppm CuO are 7 days and 3 days.

Background: Gold nanoparticles (GNPs) have diverse optical and photo-thermal properties. It is used for diagnostic imaging because of their ability to absorb near infrared (NIR) and X-rays, and their surface enhanced Raman scattering properties. Recently they are used for drug delivery and more particularly photothermal treatment. Their ability to absorb NIR energy and convert it to heat by a Surface Plasmon Resonance mechanism has made these materials promising for the treatment of tumors. GNPs having diameter higher than 1.4-1.5 nm is found nontoxic to the environment. Methods: In the present work, polymer anchored GNPs are synthesized by reducing AuIII to Au0 in presence of either chitosan or polyvinyl alcohol, which act as in situ reducers cum stabilizers. Microscopic techniques (TEM, SEM and DLS) are used to analyse the size, surface morphology and size distribution respectively. The unique mucoadhesive properties of chitosan particularly make the system promising with respect to antimicrobial (anti-bacteria as well as anti-fungus) activities. An attempt has been made to understand the mechanistic path involved in antimicrobial activities. Antimicrobial potential of chitosan anchored gold nanoparticles (GNPc) are noticed even at very low dose. Results: The results of bio-chemical analysis (MDA, NBT, DNA fragmentation and overexpression of heat shock protein) clearly explain antimicrobial activities. Additionally, gold chitosan systems interact with microbial DNA and inhibit the action of DNA repair enzyme. Interestingly, in vitro (rat peritoneal MФ) or in vivo (Wistar rat) analysis exhibits negligible cytotoxicy. Conclusion: Thus the synthesized material (particularly GNPc) is promising as an effective nano therapeutic agent.

Aim: The aim of this study was to develop effective topical antifungal formulation containing sertaconazole nitrate. Background: Sertaconazole nitrate, a topical antifungal, was incorporated in solid-liquid lipid nanostructures and gelled further for topical application. Objective: The objective of this investigation was to develop a topical formulation containing sertaconazole nitrate which was incorporated in the solid-state of the matrix to prolong the release in deep skin infection and hence reduce the application frequency. Methods: The nanostructured lipid carriers of sertaconazole nitrate were developed by high-speed homogenization followed by ultrasonication using Estosoft-GTS® (glyceryl tristearate) as a solid lipid, oleic acid as liquid lipid and Tween 80 as an emulsifier. The central composite design was used to optimize total lipid concentration and fraction of liquid lipid in the total lipid and its effect on entrapment efficiency and drug release was determined. Results: The carrier particles had an average size of 366.3 nm; entrapment efficiency in between 50.66% to 87.36%; cumulative drug release up to 92.90% and zeta potential of 7.43 mV. Characterization by FTIR indicated no negative interaction between drug and excipients, XRD showed the disappearance of crystalline peaks of the encapsulated drug while DSC revealed complete solubilization of the drug. About 99.6% of the drug was estimated by HPLC method. The drug release from gel and cream was 25.04% and 72.97% respectively. The lipid and gel excipients did not interfere with the antifungal activity of the drug. Conclusion: The developed nanocarriers loaded gel was stable. It prolonged the drug release (for 24 h) than marketed cream. It could be a promising concept for the topical delivery of antifungal and anti-inflammatory materials.

Introduction: The encapsulations of phytochemical compounds within nanoparticles are attracting interest as a novel effective strategy to induce bacterial damage regardless of antibiotic sensitivity. Objective: The purpose of this study is to evaluate the antibacterial activities of different extracts of Moringa oleifera combined with alginate nanoparticles (ALg NPs) against different pathogenic bacteria. Methods: The Moringa-ALg NPs were characterized by dynamic light scattering, zeta potential, and FTIR. In addition to that, the antimicrobial activities were assessed by using the agar well diffusion method. Moreover, the scanning electron microscope (SEM) was utilized to examine the ultrastructural changes induced in bacteria by Moringa-ALg NPs. Results: In this study, the Moringa-ALg NPs have a hydrodynamic diameter of 12 nm and zeta potential of -56 mV. The FTIR results indicatde the successful encapsulation of Moringa within ALg NPs. On the other hand, the Moringa-ALg NPs exhibited excellent antimicrobial activity against all examined pathogens as compared to pure Moringa extracts. Furthermore, the SEM images revealed that the bacterial cells exposed to Moringa-ALg NPs had an irregular and wrinkled appearance. Conclusion: In summary, these results suggested that the Moringa-ALg NPs could be used as a powerful antibacterial agent against a wide range of microbes.