Nanoparticle System Research Articles

Bioresponsive hydroxyethyl starch-flurbiprofen nanoparticles targeted to inflammatory microenvironments for post-operative pain management

Post-operative pain can hinder post-operative recovery by activating the neuroendocrine stress response to surgery, caused by inflammation. Preemptive analgesia using flurbiprofen preoperatively is a potential treatment option to avoid hyperalgesia and prevent post-operative pain. However, the hydrophobicity and short in vivo elimination half-life of flurbiprofen are limitations. In this study, a strategy is presented for targeting inflammatory microenvironments using bioresponsive nanoparticles that simultaneously alleviate inflammation and inhibit hyperalgesia, effectively managing post-operative pain in rats. Our study demonstrates that flurbiprofen-conjugated hydroxyethyl starch can self-assemble into nanoparticles in water, imparting flurbiprofen with higher solubility in water and a longer half-life. Additionally, these biocompatible flurbiprofen-conjugated hydroxyethyl starch nanoparticles accumulate in the incision. Pathological analysis of nerves indicates that hyperalgesia was effectively inhibited by the preoperative administration of HES-Flurbiprofen nanoparticles in the rat incisional pain model. This hydroxyethyl starch-based nanoparticle system also suggests a promising and straightforward strategy for developing biocompatible and bioresponsive formulations for post-operative pain management.

Magnetic irreversibility and magnetization processes in Ni5Al3/NiO core/shell nanoparticle system

This work brings out many interesting facets of magnetism in the Ni5Al3/NiO core/shell nanoparticle system. Theweakandstrongmagnetic irreversibility lines (TWI(H)andTSI(H)) reproduce the previously reportedH - Tphase diagram at fieldsH⩽30 Oe, but strong departures occur forH > 30 Oe. Comparison with the theoretically predictedH - Tphase diagram allows us to identifyTWIwithTCG+SG, where the paramagnetic (PM)-chiral glass (CG) and PM-spin glass (SG) phase transitions occursimultaneously, andTSIwithTSG, the temperature at which transition to the replica symmetry breakingSGstate takes place. TheTSI(H)transition line abruptly ends at the point (H≃30 Oe,T≃90K). AsHexceeds 30 Oe, a new transition appears which gets completely suppressed at fieldsH>1 kOewhere the magnetic irreversibility ceases to exist. Nointrinsiclong-range ferromagnetic ordering exists but fields as low as 3 kOe suffice to induce long-range ferromagnetic order. At fixed temperatures, the magnetocrystalline anisotropy fluctuations essentially govern the 'approach-to-saturation' in magnetization for fields in the range 3 - 70 kOe. The present nanocrystalline system behaves as an isotropic system with random easy axis in which the magnetization reversal occurs through the coherent rotation of the magnetizations of weakly-interacting single-domain Ni5Al3particles. Saturation magnetization, likeM(T) atH⩾2 kOe, exhibits an anomalous upturn at temperatures below ≈ 30 K. This upturn is associated with the anomalous softening of spin-wave modes which results in the thermal excitation of a large number of non-equilibrium (finite lifetime) magnons. At sub-Kelvin temperatures, these magnons undergo Bose-Einstein condensation.

Rational optimization of glycoprotein E (gE)-encoding mRNA for improved Varicella-zoster Virus mRNA vaccine development

The past decades have seen increasingly rapid advances in the field of mRNA technology and its successful applications in prophylactic vaccine development [1,2]. Recently, we reported on the development of a novel Varicella-zoster virus (VZV) mRNA vaccine (named as ZOSAL) that contains mRNAs encoding for full-length gE immunogen (623 aa) encapsulated into a novel lipid nanoparticle (LNP) system [3]. In mice and rhesus macaques, ZOSAL induced superior virus-specific immunity over licensed subunit vaccine Shingrix, which potentiated the power of mRNA platform in next-generation VZV vaccine development [3].

Paracellular Delivery of Protein Drugs with Smart EnteroPatho Nanoparticles.

A general platform for the safe and effective oral delivery of biologics would revolutionize the administration of protein-based drugs, improving access for patients and lowering the financial burden on the health-care industry. Because of their dimensions and physiochemical properties, nanomaterials stand as promising vehicles for navigating the complex and challenging environment in the gastrointestinal (GI) tract. Recent developments have led to materials that protect protein drugs from degradation and enable controlled release in the small intestine, the site of absorption for most proteins. Yet, once present in the small intestine, the protein must transit through the secreted mucus and epithelial cells of the intestinal mucosa into systemic circulation, a process that remains a bottleneck for nanomaterial-based delivery. One attractive pathway through the intestinal mucosa is the paracellular route, which avoids cell trafficking and other degradative processes in the interior of cells. Direct flux between cells is regulated by epithelial tight junctions (TJs) that seal the paracellular space and prevent protein flux. Here, we describe a smart nanoparticle system that directly and transiently disrupts TJs for improved protein delivery, an unrealized goal to-date. We take inspiration from enteropathogenic bacteria that adhere to intestinal epithelia and secrete inhibitors that block TJ interactions in the local environment. To mimic these natural mechanisms, we engineer nanoparticles (EnteroPatho NPs) that attach to the epithelial glycocalyx and release TJ modulators in response to the intestinal pH. We show that EnteroPatho NPs lead to TJ disruption and paracellular protein delivery, giving rise to a general platform for oral delivery.

Exploring mesophase formation: Structural characterization approaches in a soft sphere model

This study employs Molecular Dynamics simulations to enhance the structural characterization of sphere mixture systems, focusing on local order parameters to identify order-disorder transitions within lamellar and hexagonal mesophases. The structural characterization included the use of neural networks and the search for clusters with topological order. We have identified the order-disorder transition at a characteristic temperature TOD, effectively captured by the structural parameters analyzed. Below TOD, the system organizes into an ordered mesophase, while above this temperature, it transitions into an isotropic liquid state. Moreover, within the isotropic region, we observe that the liquid begins to form clusters. This clustering phenomenon becomes evident below a specific temperature, denoted as T⁎. At T⁎, there are noticeable changes in the volume versus temperature curves, indicating a process of micellization or clustering in the system. The structural parameters used in our study also register this behavioral change at T⁎, further supporting the occurrence of this phenomenon. Additionally, our analysis of the overlap in detecting ordered particles between the two structural parameters using the Sørensen-Dice similarity coefficient reveals a significant spatial correlation in the isotropic phase, with a correlation higher than what would be expected in a random case. This indicates that both neural networks and topological cluster classification detect statistically similar ordered regions in the isotropic phase, highlighting the clustering. Our findings reveal that the structural parameters effectively capture both the order-disorder transition at TOD and the clustering process at T⁎. These results provide valuable insights into the self-assembly mechanisms and phase behavior in this soft-sphere model, advancing our understanding of self-assembly processes in material science, particularly in exploring phase behavior in mesogenic nanoparticle systems.

Glutathione-modified hyaluronic acid nanoparticles for the targeted delivery of sulfasalazine to neuroblastoma

A new nanoparticulate system based on hyaluronic acid for targeted delivery of sulfasalazine (SSA) to neuroblastoma was synthetized and characterized. The SSA-containing nanoparticles were obtained by nanoprecipitation and then surface-modified with PEG chains and glutathione using EDC/NHS chemistry. The resulting hydrogel nanospheres had a hydrodynamic diameter of about 165 nm and were colloidally stable. AFM and cryo-TEM images confirmed their spherical shape, nanometer size and low aggregation tendency. SSA was effectively encapsulated in the polymer matrix and released from the nanoparticles in a controlled manner. Bioassays showed that our nanoparticles were non-hemolytic, efficiently taken up by neuroblastoma cells and, compared to free SSA, showed superior cytotoxicity against SH-SY5Yneuroblastoma cells at low concentrations. Both the release profile and biological studies indicate the high potential of our delivery system in neuroblastoma therapy.

Surface engineering of metal-organic framework nanoparticles-based miRNA carrier: Boosting RNA stability, intracellular delivery and synergistic therapy

MicroRNAs (miRNAs) are small noncoding RNAs that are critical for the regulation of multiple physiological and pathological processes, thus holding great clinical potential. However, the therapeutic applications of miRNAs are severely limited by their biological instability and poor intracellular delivery. Herein, we describe a dual-layers surface engineering strategy to design an efficient miRNA delivery nanosystem based on metal–organic frameworks (MOFs) incorporating lipid coating. The resulting nanoparticle system was demonstrated to protect miRNA from ribonuclease degradation, enhance cellular uptake and facilitate lysosomal escape. These ensured effective miRNA mediated gene therapy, which synergized with MOF-specific photodynamic therapy and pre-encapsulated doxorubicin (Dox) chemotherapy to provide a multifunctional with therapeutic effectiveness against cencer cells The mechanisms of miRNA binding and Dox loading were revealed, demonstrating the potential of the present MOFs surface-engineered strategy to overcome their inherent pore-size restriction for macromolecular miRNA carrying, enableefficient co-delivery. In vitro studies revealed the potential of our multifunctional system for miRNA delivery and the demonstrated the therapeutic effectiveness against cancer cells, thereby providing a versatile all-in-one MOFs strategy for delivery of nucleic acids and diverse therapeutic molecules in synergistic therapy.

Computational and Experimental Investigations of the Au and NiOOH Interface in the Oxygen Evolution Reaction

The transition to renewable energy sources is crucial for combating climate change, and hydrogen (H2) is a promising clean fuel. Electrolysis of water, specifically the oxygen evolution reaction (OER), is a key process for producing H2. Prior experimental results have shown that gold (Au) could improve the apparent activities of the OER electrocatalysts such as nickel hydroxide (Ni(OH)2) in alkaline electrolytes.1-3 However, the detailed interfacial atomic structure and mechanisms of the increased catalytic activity remain poorly understood.To understand the interfacial effect between Au and Ni(OH)2 in the OER process, our research uses the model system of Au nanoparticles (NPs) and nickel oxyhydroxide (NiOOH), which is the active phase of Ni(OH)2 layers in the OER, to investigate their interfacial interactions with both experimental and computational approaches. We hypothesize that the Au NPs on NiOOH enhances the OER activity by promoting electron transfer at the interface. Our studies involve computational analysis using Density Functional Theory (DFT) calculations to obtain the local density of states (LDOS), which can help us better visualize and compare the local electronic structure of NiOOH in the presence and in the absence of AuNPs. Two architectures of the Au and NiOOH interface will be investigated: Au NPs on a NiOOH film and NiOOH NPs on a Au film.Additionally, Bader analysis is employed to determine the Bader charge, offering a more detailed understanding of how electrons are distributed across the AuNPs/NiOOH interface. Furthermore, the catalytic efficacy of AuNPs on NiOOH is assessed through electrodepositions followed by cyclic voltammetry(CV) measurements. The experimental and computational results will be directly compared, and this research is expected to contribute to the insights of substrate and catalyst interactions for design of more efficient electrocatalysts.

(Invited) Tuning Selective CO2 Electrohydrogenation Under Mid Temperature and Pressure

To address rising environmental concerns and energy challenges, it is highly desirable to develop green technologies for a sustainable future. Hydrogenation reactions are essential processes in the chemical industry, giving access to a variety of valuable compounds. Electrochemical CO2 hydrogenation using renewable electricity is considered one of the most promising pathways to reach the environmental economics. Among various electrochemical devices, a solid state electrolyzer working at intermediate temperatures has the advantages of high reaction rates and low overpotentials. As CO2 molecules is quite stable, it is critical to develop electrocatalysts with high activity to reduce electricity engagement. Also, CO2 hydrogenation has multiple pathways which normally results in low selectivity for a target product. A tunable electrocatalyst with high selectivity to different products is desirable for CO2 conversion reactions. Heterostructured nanomaterials attracts great attentions in electrochemical systems. With careful design, they can show very high activity and selectivity towards an electrochemical reaction pathway. In this work, we combine theoretical simulations, including density functional theory (DFT) and ab initio molecular dynamics (AIMD) calculations, with experimental methods (characterizations and electrochemical measurements) for rational design of highly efficient heterostructured nanomaterials for CO2 hydrogenations. We studied the strong metal-support interaction (SMSI) in a doped CeO2 supported noble metal nanoparticles (NPs) system using theoretical calculations. The results indicate that SMSI largely depends on chemical conditions of the support and particle size of dispersed metal NPs. By tuning the SMSI, we can successfully change the catalytic activity and selectivity towards CO2 hydrogenation reactions. Based on these findings, we designed tunable heterostructured nanomaterials for efficient hydrogenation reactions at intermediate temperatures. These predictions were further confirmed by experimental method. By using a combination of high-throughput theoretical calculations and electrochemical measurements, we successfully developed highly active catalysts for electrochemical CO2 hydrogenation reactions. This framework is also applicable to other electrochemical systems using heterostructured materials.

(Invited) Perspectives from in Situ spectroscopy on the Molecular-Level Interactions of Carbon Dioxide in Nanomaterials for Capture and Conversion

Understanding the molecular level foundations of CO2 capture and conversion might unveil design strategies for efficient materials for these key decarbonization technologies. The control over the reaction channel in the complex network of reactions to produce selectively and on-demand chemicals from CO2 via electrocatalysis is appealing to scientists worldwide on a fundamental and technological level. Operando techniques have become very popular to help achieve this goal as demonstrated by a flourishing number of dedicated studies [1-3] and other initiatives for discussion [4-6]. In this contribution, I will present recent work on the spectroscopic characterisation of the CO2 interaction with several prototypical nanostructural systems of relevance, [7-11] emphasising characteristic spectroscopic fingerprints and their critical assessment. This contribution aims to discuss opportunities and current limitations encountered in situ X-ray methods to extract mechanistic insights.[1] Y. Han, H. Zhang, Y. Yu, Z. Liu, In Situ Characterization of Catalysis and Electrocatalysis Using APXPS, ACS Catalysis, 11 (2021), 1464-1484.[2] V. Pfeifer, M. Hävecker, J. J. Velasco Vélez, A. Knop-Gericke, R. Schlögl, R. Arrigo, An in situ electrochemical cell for studying OER materials, Topics in Catalysis, 61 (2019), 2064-2084.[3] G. Held, F. Venturini, D. C. Grinter, P. Ferrer, R. Arrigo, L. Deacon, W. Quevedo Garzon, K. Roy, A. Large, C. Stephens, A. Watts, P. Larkin, M. Hand, H. Wang, L. Pratt, J. J. Mudd, T. Richardson, S. Patel, M. Hillman and S. Scott, Ambient-pressure end station of the Versatile Soft X-ray (VerSoX) beamline at Diamond Light Source, J. Synchrotron Rad., 27 (2020), 1153-1166.[4] R. Arrigo, A. Logsdail, L. Torrente-Murciano, Highlights from Faraday Discussion on Designing Nanoparticle Systems for Catalysis, London, UK, May 2018, (Conference Report) Chem. Commun., 2018, 54, 9385-9393DOI: 10.1039/C8CC90324G;[5] R. Arrigo et al., The challenges of characterising nanoparticulate catalysts: general discussion Faraday Discussion, 208 (2018), 339-394.[6] C. R. A. Catlow, P. wells, D. Gianolio Synchrotron radiation techniques in catalytic science, Phys. Chem. Chem. Phys., 22 (2020), 18745-18746.[7] R. Arrigo, R. Blume, V. Streibel, C. Genovese, A. Roldan, M. E. Schuster, C. Ampelli, S. Perathoner, J.-J. Velasco-Vélez, M. Hävecker, A. Knop-Gericke, R. Schlögl, G. Centi, Dynamics at Polarized, Carbon Dioxide/Iron Oxyhydroxide Interfaces Unveil the Origin of Multicarbon Product Formation, ACS Catalysis, 12 (2021) 411-430.[8] J.-J. Velasco-Vélez, T. Jones, D. Gao, E. Carbonio, R. Arrigo, C.-J. Hsu, Y.-C. Huang, C.-L. Dong, J.-M. Chen, J.-F. Lee, P. Strasser, B. Roldan Cuenya, R. Schlögl, A. Knop-Gericke, C.-H. Chuang, The Role ofthe Copper Oxidation State in the Electrocatalytic Reduction of CO2 into Valuable Hydrocarbons, ACS Sustainable Chem. Eng., 7 (2019), 1485–1492.[9] J.-J. Velasco-Vélez, C.-H. Chuang, D. Gao, Q. Zhu, D. Ivanov, H. S. Jeon, R. Arrigo, R. V. Mom, E. Stotz, H.-L. Wu, T. E. Jones, B. Roldan Cuenya, A. Knop-Gericke, R. Schlögl, On the activity/selectivity and phase stability of thermally grown copper oxides during the electrocatalytic reduction of CO2, ACS Catalysis, 10 (2020) 11510-11518.[10] J-J. Velasco-Velez, R.V. Mom, L.-E. Sandoval-Diaz, L. J. Falling, C.-H. Chuang, D. Gao, T. E. Jones, Q. Zhu, R. Arrigo, B. Roldan Cuenya, A. Knop-Gericke, T. Lunkenbein, R. Schlögl, Revealing the ActivePhase of Copper during the Electroreduction of CO2 in Aqueous Electrolyte by Correlating In Situ X-ray Spectroscopy and In Situ Electron Microscopy, ACS Energy Lett., 5 (2020), 2106–2111.[11] R. Arrigo, R. Blume, A. Large, J.-J. Velesco-Velez, M., Haevecker, A. Knop-Gericke, G. Held, Dynamics over a Cu-graphite electrode during the gas-phase CO2 reduction investigated by APXPS, Faraday Discuss., 236 (2022) 126-140.

Drug Loading in Chitosan-Based Nanoparticles.

Chitosan nanoparticles (CSNPs) are promising vehicles for targeted and controlled drug release. Recognized for their biodegradability, biocompatibility, low toxicity, and ease of production, CSNPs represent an effective approach to drug delivery. Encapsulating drugs within nanoparticles (NPs) provides numerous benefits compared to free drugs, such as increased bioavailability, minimized toxic side effects, improved delivery, and the incorporation of additional features like controlled release, imaging agents, targeted delivery, and combination therapies with multiple drugs. Keys parameters in nanomedicines are drug loading content and drug loading efficiency. Most current NP systems struggle with low drug loading, presenting a significant challenge to the field. This review summarizes recent research on developing CSNPs with high drug loading capacity, focusing on various synthesis strategies. It examines CSNP systems using different materials and drugs, providing details on their synthesis methods, drug loadings, encapsulation efficiencies, release profiles, stability, and applications in drug delivery. Additionally, the review discusses factors affecting drug loading, providing valuable guidelines for future CSNPs' development.

Topical calcineurin and mammalian target of rapamycin inhibitors in inflammatory dermatoses: Current challenges and nanotechnology‑based prospects (Review).

Topical therapy remains a critical component in the management of immune‑mediated inflammatory dermatoses such as psoriasis and atopic dermatitis. In this field, macrolactam immunomodulators, including calcineurin and mammalian target of rapamycin inhibitors, can offer steroid‑free therapeutic alternatives. Despite their potential for skin‑selective treatment compared with topical corticosteroids, the physicochemical properties of these compounds, such as high lipophilicity and large molecular size, do not meet the criteria for efficient penetration into the skin, especially with conventional topical vehicles. Thus, more sophisticated approaches are needed to address the pharmacokinetic limitations of traditional formulations. In this regard, interest has increasingly focused on nanoparticulate systems to optimize penetration kinetics and enhance the efficacy and safety of topical calcineurin and mTOR inhibitors in inflamed skin. Several types of nanovectors have been explored as topical carriers to deliver tacrolimus in both psoriatic and atopic skin, while preclinical data on nanocarrier‑based delivery of topical sirolimus in inflamed skin are also emerging. Given the promising preliminary outcomes and the complexities of drug delivery across inflamed skin, further research is required to translate these nanotherapeutics into clinical settings for inflammatory skin diseases. The present review outlined the dermatokinetic profiles of topical calcineurin and mTOR inhibitors, particularly tacrolimus, pimecrolimus and sirolimus, focusing on their penetration kinetics in psoriatic and atopic skin. It also summarizes the potential anti‑inflammatory benefits of topical sirolimus and explores novel preclinical studies investigating dermally applied nanovehicles to evaluate and optimize the skin delivery, efficacy and safety of these 'hard‑to‑formulate' macromolecules in the context of psoriasis and atopic dermatitis.

Establishment of nanoparticle screening technique: A pivotal role of sodium carboxymethylcellulose in enhancing oral bioavailability of poorly water-soluble aceclofenac

A novel nanoparticle screening technique was established to mostly enhance the aqueous solubility and oral bioavailability of aceclofenac using nanoparticle systems. Among the polymers investigated, sodium carboxymethylcellulose (Na-CMC) showed the greatest increase in drug solubility. Utilizing spray-drying technique, the solvent-evaporated solid dispersion (SESD), surface-attached solid dispersion (SASD), and solvent-wetted solid dispersion (SWSD) were prepared using aceclofenac and Na-CMC at a weight ratio of 1:1 in 50 % ethanol, distilled water, and ethanol, respectively. Using Na-CMC as a solid carrier, an aceclofenac-loaded liquid self-emulsifying drug delivery system was spray-dried and fluid-bed granulated together with microcrystalline cellulose, producing a solid self-nanoemulsifying drug delivery system (SNEDDS) and solid self-nanoemulsifying granule system (SNEGS), respectively. Their physicochemical properties and preclinical assessments in rats were performed. All nanoparticles exhibited very different properties, including morphology, crystallinity, and size. As a result, they significantly enhanced the solubility, dissolution, and oral bioavailability in the following order: SNEDDS ≥ SNEGS > SESD ≥ SASD ≥ SWSD. Based on our screening technique, the SNEDDS was selected as the optimal nanoparticle with the highest bioavailability of aceclofenac. Thus, our nanoparticle screening technique should be an excellent guideline for solubilization research to improve the solubility and bioavailability of many poorly water-soluble bioactive materials.

Amino-functionalised mesoporous silica nanoparticles for the delivery of isoniazid and its metal complexes

The effective delivery of poor water-soluble anti-tubercular drugs such as isoniazid to their target sites is a major factor that has made it difficult for tuberculosis to be eradicated. Isoniazid derivatives and nano-particulate drug delivery systems are explored as one way to address this limitation. This study investigated the use of amino-functionalised mesoporous silica nanoparticles (MCM-41) as nano-carriers for the delivery of isoniazid-based metal complexes, Cu–INH and Fe–INH. The Sol-gel method was used to synthesise the nano-carriers, which produced a series of well-ordered nano-carriers. Their physicochemical properties were modified through surface functionalisation with amino groups via post-grafting synthesis. The isoniazid-based metal complexes were incorporated into the nano-carriers using rotary evaporation. The nano-carriers were characterised using X-ray diffraction (XRD), Zeta potential, Fourier Transmission Infra-red (FT-IR), Brunaeur Emmett Teller (BET), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Thermogravimetric analysis (TGA). These characterisation techniques confirmed the successful surface functionalisation of the nano-carriers with amino groups and their encapsulation with INH, Cu–INH and Fe–INH. The amino-functionalised nano-carriers were observed to have the highest drug loading capacities and entrapment efficiencies within the range of 7.85%–19.31 % and 39.26%–96.53 %, respectively. The release rates of INH, Cu–INH, and Fe–INH from the nano-carriers were also studied in Phosphate Buffer Solution (PBS) with pH of 7.4 and 5.4 using ultraviolet–visible spectroscopy. The cumulative release rates of INH, Cu–INH, and Fe–INH from their nano-carriers depended on their release media's textural properties and environmental conditions. Amino functionalised nano-carriers had high release rates, with A-MCM-41+Cu–INH having the highest of 37.09 % in PBS at 5.4 after 24 h. The cumulative data obtained was fitted into Zero order, First order, Hixson Crowell, Higuchi, Korsmeyer-Peppas and Weibull models. The Hixson Crowell, Korsmeyer-Peppas, and Weibull models fitted well with correlation coefficients (R2) of 0.9813, 0.9769 and 0.9802, respectively, for MCM-41+INH in PBS of pH 5.4.

Inhaled Nanoparticulate Systems: Composition, Manufacture and Aerosol Delivery.

An increasing growth in nanotechnology is evident from the growing number of products approved in the past decade. Nanotechnology can be used in the effective treatment of several pulmonary diseases by developing therapies that are delivered in a targeted manner to select lung regions based on the disease state. Acute or chronic pulmonary disorders can benefit from this type of therapy, including respiratory distress syndrome (RDS), chronic obstructive pulmonary disease (COPD), asthma, pulmonary infections (e.g. tuberculosis, Yersinia pestis infection, fungal infections, bacterial infections, and viral infections), lung cancer, cystic fibrosis (CF), pulmonary fibrosis, and pulmonary arterial hypertension. Modification of size and surface property renders nanoparticles to be targeted to specific sites, which can serve a vital role in innovative pulmonary drug delivery. The nanocarrier type chosen depends on the intended purpose of the formulation and intended physiological target. Liquid nanocarriers and solid-state nanocarriers can carry hydrophilic and hydrophobic drugs (e.g. small molecular weight drug molecules, large molecular weight drugs, peptide drugs, and macromolecular biological drugs), while surface modification with polymer can provide cellular targeting, controlled drug release, and/or evasion of phagocytosis by immune cells, depending on the polymer type. Polymeric nanocarriers have versatile architectures, such as linear, branched, and dendritic forms. In addition to the colloidal dispersion liquid state, the various types of nanoparticles can be formulated into the solid state, offering important unique advantages in formulation versatility and enhanced stability of the final product. This chapter describes the different types of nanocarriers, types of inhalation aerosol device platforms, liquid aerosols, respirable powders, and particle engineering design technologies for inhalation aerosols.

Multifunctional nanoparticle system provides both diagnostic, therapeutic applications

Multifunctional nanoparticle system provides both diagnostic, therapeutic applications

A label-free G-quadruplex aptamer/gold nanoparticle-based colorimetric biosensor for rapid detection of bovine viral diarrhea virus genotype 1.

Bovine viral diarrhea virus (BVDV) is the cause of bovine viral diarrhea disease, one of the most economically important livestock diseases worldwide. The majority of BVD disease control programs rely on the detection and then elimination of persistent infection (PI) cattle, as the continuing source of disease. The main purpose of this study was to design and develop an accurate G-quadruplex-based aptasensor for rapid and simple detection of BVDV-1. In this work, we utilized in silico techniques to design a G-quadruplex aptamer specific for the detection of BVDV-1. Also, the rationally designed aptamer was validated experimentally and was used for developing a colorimetric biosensor based on an aptamer-gold nanoparticle system. Firstly, a pool of G-quadruplex forming ssDNA sequences was constructed. Then, based on the stability score in secondary and tertiary structures and molecular docking score, an aptamer (Apt31) was selected. In the experimental part, gold nanoparticles (AuNPs) with an average particle size of 31.7 nm were synthesized and electrostatically linked with the Apt31. The colorimetric test showed that salt-induced color change of AuNPs from red to purple-blue occurs only in the presence of BVDV-Apt31 complex, after 20 min. These results approved the specificity of Apt31 for BVDV. Furthermore, our biosensor could detect the virus at as low as 0.27 copies/ml, which is an acceptable value in comparison to the qPCR method. The specificity of the aptasensor was confirmed through cross-reactivity testing, while its selectivity was confirmed through plasma testing. The sample analysis showed 90% precision and 94% accuracy. It was concluded that the biosensor was adequately sensitive and specific for the detection of BVDV in plasma samples and could be used as a simple and rapid method on the farm.

Design, synthesis and anti-oxidant activities of novel 1,2,3,4-tetrazine, 1,2,3-triazoles and coumarin derivatives and their nanoparticular encapsulation

Nitrogen-containing heterocyclic compounds are currently used for a number of pharmaceutical and agricultural applications because they have biological activities such as antimicrobial, antiviral, antituberculosis, anticancer, analgesic, antioxidant, anti-inflammatory and antidepressant. 1,2,3,4-Tetrazines and 1,2,3-triazoles are examples of high-nitrogen heterocyclic compounds. Coumarins, on the other hand, are lactones that form a group of oxygenated heterocyclic compounds found in plants. In this article, two analogs of 1,2,3,4-tetrazine, two analogs of 1,2,3-triazole and five analogs of coumarin were designed and synthesized. Their chemical structures were characterized by detecting their FTIR, 1H-NMR, and 13C-NMR (APT) spectra. The antioxidant activities of all synthesized molecules were compared at a fixed concentration (0.25 mg ml−1) using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. Molecules 9c and 9e, which showed the highest antioxidant activity, were loaded into PLGA (poly(lactic-co-glycolic) acid) nanoparticles using the oil in water (o/w) single emulsion solvent evaporation method as a model study. Synthesized nanoparticles characterized for particle size, zeta potential, functional groups, morphology, and release properties. Particle size and zeta potential of 9c/NP were determined as 216.1 ± 8.944 nm and −14.1 ± 2.40 mV, respectively. The particle size and zeta potential for 9e/NP were measured as 222.0 ± 12.490 nm and −12.4 ± 1.42 mV respectively. The study results obtained on model nanoparticle systems with elucidated physicochemical properties may have the potential to provide a promising basis for oxidative stress-related diseases in the future.

Gum Arabic-assisted green synthesis of gold nanoparticles as fluorescence modulator for potential analytical applications

Aim: To demonstrate a simple, eco-friendly, and cost-effective green method to synthesize gold nanoparticles (AuNPs) using the aqueous extract of gum Arabic (GA) as a reducing and stabilizing agent. Methods: Green synthesis of nanoparticles, characterization by absorption, infra-red and fluorescence spectroscopy. Results: The absorption spectrum (UV-Vis) showed an absorption peak ~522 nm corresponding to the surface plasmon resonance (SPR) absorption peak of AuNPs. Transmission electron microscopy (TEM) images revealed spherical-shaped nanoparticles with an average size of 15 nm. Fourier transform infrared (FTIR) analysis showed that the nanoparticles are coated with organic compounds that are present in GA. The fluorescence quenching properties of the AuNPs were assessed by monitoring their effects on fluorescence intensity of coumarin 153 (C153) dye. The fluorescence of the dye decreased with an increase in concentration of the nanoparticles. Upon addition of the protein bovine serum albumin (BSA) to the mixture the fluorescence increased (recovery) again. Conclusions: The fluorescence quenching and recovery (turn-on/off system) is a valuable method for protein detection in solution. By observing the effect of BSA on the quenched fluorescence, this nanoparticle system shows promise in biomedicine, drug delivery and environmental monitoring.

Optimization of Interfacial Properties Improved the Stability and Activity of the Catalase Enzyme Immobilized on Plastic Nanobeads.

The immobilization of catalase (CAT), a crucial oxidoreductase enzyme involved in quenching reactive oxygen species, on colloids and nanoparticles presents a promising strategy to improve dispersion and storage stability while maintaining its activity. Here, the immobilization of CAT onto polymeric nanoparticles (positively (AL) or negatively (SL) charged) was implemented directly (AL) or via surface functionalization (SL) with water-soluble chitosan derivatives (glycol chitosan (GC) and methyl glycol chitosan (MGC)). The interfacial properties were optimized to obtain highly stable AL-CAT, SL-GC-CAT, and SL-MGC-CAT dispersions, and confocal microscopy confirmed the presence of CAT in the composites. Assessment of hydrogen peroxide decomposition ability revealed that applying chitosan derivatives in the immobilization process not only enhanced colloidal stability but also augmented the activity and reusability of CAT. In particular, the use of MGC has led to significant advances, indicating its potential for industrial and biomedical applications. Overall, the findings highlight the advantages of using chitosan derivatives in CAT immobilization processes to maintain the stability and activity of the enzyme as well as provide important data for the development of processable enzyme-based nanoparticle systems to combat reactive oxygen species.