Carbon-Based Nanomaterials 4.0.

Research on carbon-based nanomaterials, such as carbon nanotubes and graphene and its derivatives, has experienced exponential development in recent years [...].

QbD-Based Fabrication of Biomimetic Hydroxyapatite Embedded Gelatin Nanoparticles for Localized Drug Delivery against Deteriorated Arthritic Joint Architecture.

Biomaterials such as nanohydroxyapatite and gelatin are widely explored to improve damaged joint architecture associated with rheumatoid arthritis (RA). Besides joint damage, RA is associated with inflammation of joints and cartilage, which potentiates the need for both bone nucleation and therapeutic intervention. For such purpose, a modified nanoprecipitation method is used herein to fabricate tofacitinib (Tofa)-loaded nanohydroxyapatite (nHA) embedded gelatin (GLT) nanoparticles (NPs) (Tofa-nHA-GLT NPs). The quality by design (QbD) approach is chosen to assess the key parameters that determine the efficiency of the NPs, and are further optimized via Box-Behnken design of experiment. The particle size, polydispersity, zeta potential, and encapsulation efficiency (EE) of the prepared NPs are found to be 269 nm, 0.18, -20.5 mV, and 90.7%, respectively. Furthermore, the NPs have improved stability, skin permeability, and a sustained drug release pattern at pH 6.5 (arthritic joint pH). Moreover, rhodamine-B loaded nHA-GLT NPs demonstrates considerably higher cellular uptake by the murine-derived macrophages than free rhodamine-B solution. In vitro, cell-based experiments confirm the good cell biocompatibility with insignificant toxicity. Thus, QbD-based approach has successfully led to the development of Tofa-nHA-GLT NPs with the potential to target inflamed arthritic joint.

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) Bionanocomposites with Crystalline Nanocellulose and Graphene Oxide: Experimental Results and Support Vector Machine Modeling.

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a biodegradable and biocompatible bacterial copolymer used in the biomedical and food industries. However, it displays low stiffness and strength for certain applications. This issue can be solved via reinforcement with nanofillers. In this work, PHBHHx-based bionanocomposites reinforced with different loadings of crystalline nanocellulose (CNC) and graphene oxide (GO) were developed by a green and straightforward solution casting technique. Their crystalline nature and surface topography were explored via X-ray diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM), respectively, their composition was corroborated via Fourier-transformed infrared spectroscopy (FTIR), and their crystallization and melting behavior were determined via differential scanning calorimetry (DSC). The nanofillers had a nucleating role, raising the crystallization temperature of the polymer, whilst hardly any changes were found in the melting temperature. Further, significant enhancements in the stiffness, strength, and thermal stability of the PHBHHx matrix were observed with the incorporation of both nanofillers, which was attributed to a synergic effect. The mechanical properties for various concentrations of CNC and GO were accurately predicted using a machine learning (ML) model in the form of a support vector machine (SVM). The model performance was evaluated in terms of the mean absolute error (MAE), the mean square error (MSE), and the correlation coefficient (R2). These bio-based nanocomposites are a valuable alternative to conventional petroleum-based synthetic polymeric materials used nowadays for biomedicine and food packaging applications.

Polymers and Nanotechnology for Industry 4.0.

The term "polymer" derives from the Greek words "πολύς" meaning "many, much" and "µÎ­ρος" meaning "part", and was proposed in 1833 by Jöns Jacob Berzelius, albeit with a different definition from the current IUPAC definition [...].

Development of chitosan based ß-carotene mucoadhesive formulation for skin cancer treatment.

Mucopermeating nanoformulations can enhance mucosal penetration of poorly soluble drugs at their target site. In this work, thiolated chitosan (TCS)-lithocholic acid (LA) nanomicelles loaded with ß-carotene, a safe phytochemical with anticancer properties, were designed to improve the pharmaceutical and pharmacological drug profile. The TCS-LA nanomicelles were characterized by FTIR to confirm the presence of the thiol group that favors skin adhesion, and to corroborate the conjugation of hydrophobic LA with hydrophilic CS to form an amphiphilic polymer derivative. Their crystalline nature and thermal behavior were investigated by XRD and DSC analyses, respectively. According to DLS and TEM, their average size was <300 nm, and their surface charge was +27.0 mV. ß-carotene entrapment and loading efficiencies were 64 % and 58 %, respectively. In vitro mucoadhesion and ex vivo mucopenetration analyses further corroborated the potential of the nanoformulation to deliver the drug in a sustained manner under conditions mimicking cancer micro-environment. Anticancer studies in mice demonstrated that the loaded nanomicelles delayed skin cancer growth, as revealed by both morphological and biochemical parameters. Based on the results obtained herein, it can be concluded that drug-loaded TCS-LA is a novel, stable, effective and safe mucoadhesive formulation of ß-carotene for the potential treatment of skin cancer.

Synthesis and Characterization of Polyhydroxyalkanoate/Graphene Oxide/Nanoclay Bionanocomposites: Experimental Results and Theoretical Predictions via Machine Learning Models.

Predicting the mechanical properties of multiscale nanocomposites requires simulations that are costly from a practical viewpoint and time consuming. The use of algorithms for property prediction can reduce the extensive experimental work, saving time and costs. To assess this, ternary poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV)-based bionanocomposites reinforced with graphene oxide (GO) and montmorillonite nanoclay were prepared herein via an environmentally friendly electrochemical process followed by solution casting. The aim was to evaluate the effectiveness of different Machine Learning (ML) models, namely Artificial Neural Network (ANN), Decision Tree (DT), and Support Vector Machine (SVM), in predicting their mechanical properties. The algorithms' input data were the Young's modulus, tensile strength, and elongation at break for various concentrations of the nanofillers (GO and nanoclay). The correlation coefficient (R2), mean absolute error (MAE), and mean square error (MSE) were used as statistical indicators to assess the performance of the models. The results demonstrated that ANN and SVM are useful for estimating the Young's modulus and elongation at break, with MSE values in the range of 0.64-1.0% and 0.14-0.28%, respectively. On the other hand, DT was more suitable for predicting the tensile strength, with the indicated error in the range of 0.02-9.11%. This study paves the way for the application of ML models as confident tools for predicting the mechanical properties of polymeric nanocomposites reinforced with different types of nanofiller, with a view to using them in practical applications such as biomedicine.

Novel chitosan/γ-alumina/carbon quantum dot hydrogel nanocarrier for targeted drug delivery.

Curcumin (CUR) is among the most natural and effective antitumor drugs for cancer treatment. These drugs have low solubility and short half-lives that reduce their effectiveness in drug release systems. Herein, a hydrogel nanocarrier containing chitosan (CS), alumina (γ-Al2O3), and carbon quantum dots (CQDs) was prepared by the water-in-oil-in-water (W/O/W) double nanoemulsion method. DLS revealed a nanocarrier size of 227 nm, with a zeta potential of -37.8 mV, which corroborates its stability. FE-SEM showed its quasi-spherical shape, FT-IR and XRD confirmed the presence of all the components in the nanocomposite and gave information about the intermolecular interactions between them and the crystalline nature of the nanocarrier, respectively. The drug loading (48 %) and entrapment efficiency (86 %) were higher than those reported previously for other CUR nanocarriers. The drug release profile revealed a controlled and stable release, and a pH-sensitive behavior, with faster CUR release in an acid environment. The breast cancer cell line was examined by cytotoxicity and cell apoptosis analyses. The results showed that the slow release over time and the programmed cell death were due to interactions between CUR and the nanocarrier. Considering the results obtained herein, CS/γAl2O3/CQDs/CUR can be considered as a promising new nanosystem for tumor treatment.

Isotropic and Anisotropic Complex Refractive Index of PEDOT:PSS.

In this work, the complex refractive indexes of seven PEDOT:PSS samples, three with isotropic behavior and four with optical anisotropy, were determined. For the anisotropic samples, the ordinary and extraordinary components of the refractive index were described. The effect of the film thickness, measurement technique and preparation method on the extinction coefficient (k) and refractive index (n) of each sample was also discussed. Important differences (up to 20% in the average n) were found among the samples investigated. In most anisotropic films, the mean value of the extraordinary component was between 7 and 10% higher than that of the ordinary. In the three isotropic films, the average k rose when the film thickness increased. Moreover, the different sets of refractive index data were fitted to three different models: the original Forouhi-Bloomer model, the Liu (2007) model and the revised version of the Forouhi-Bloomer model (2019). In general, Liu's model gave better results, with small errors in n and k (<7.81 and 4.68%, respectively, in all the cases). However, this model had seven fitting parameters, which led to significantly longer computation time than the other two models. The influence of the differences in the measurement of the complex refractive index on the simulation of the optical properties of PEDOT:PSS multilayers was discussed. The results showed that n must be known precisely to accurately calculate the light absorption in a multilayer, without ignoring the isotropic or anisotropic behavior of the material or the influence of the layer thickness on its optical properties. This study aids in the development of simulation and optimization tools that allow understanding the optical properties of PEDOT:PSS films for their potential applications in organic optoelectronic devices, such as organic solar cells.

Mannosylated preactivated hyaluronic acid-based nanostructures for bacterial infection treatment.

Salmonella Typhi is an intracellular bacterium causing a variety of enteric diseases, being typhoid fever the most common. Current modalities for treating S. typhi infection are subjected to multi-drug resistance. Herein, a novel macrophage targeting approach was developed via coating bioinspired mannosylated preactivated hyaluronic acid (Man-PTHA) ligands on a self-nanoemulsifying drug delivery system (SNEDDS) loaded with the anti-bacterial drug ciprofloxacin (CIP). The shake flask method was used to determine the drug solubility in the different excipients (oil, surfactants and co-surfactants). Man-PTHA were characterized by physicochemical, in vitro, and in vivo parameters. The mean droplet size was 257 nm, with a PDI of 0.37 and zeta potential of -15 mV. In 72 h, 85 % of the drug was released in a sustained manner, and the entrapment efficiency was 95 %. Outstanding biocompatibility, mucoadhesion, muco-penetration, anti-bacterial action and hemocompatibility were observed. Intra-macrophage survival of S. typhi was minimal (1 %) with maximum nanoparticle uptake, as shown by their higher fluorescence intensity. Serum biochemistry evaluation showed no significant changes or toxicity, and histopathological evaluation confirmed the entero-protective nature of the bioinspired polymers. Overall, results confirm that Man-PTHA SNEDDS can be employed as novel and effective delivery systems for the therapeutic management of S. typhi infection.

Green synthesis of chitosan/polyacrylic acid/graphitic carbon nitride nanocarrier as a potential pH-sensitive system for curcumin delivery to MCF-7 breast cancer cells.

A novel pH-sensitive nanocarrier containing chitosan (CS), polyacrylic acid (PAA), and graphitic carbon nitride (g-C3N4) was designed via water/oil/water (W/O/W) emulsification to administer curcumin (CUR) drug. g-C3N4 nanosheets with a high surface area and porous structure were produced via simple one-step pyrolysis process using thiourea as precursor, and incorporated into CS/PAA hydrogel. X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to assess the crystalline structure of the nanocarrier and the interactions between its components, respectively. Scanning electron microscopy (SEM) images revealed a spherical structure and confirmed the g-C3N4 impregnation into the CS/PAA matrix. Zeta potential and dynamic light scattering (DLS) provided information about the surface charge and average size distribution. High CUR loading and entrapment efficiencies were obtained, which were further improved upon addition of g-C3N4. The release kinetics of drug-loaded CS/PAA/g-C3N4 nanocomposites were investigated at pH = 5.4 and pH = 7.4, and the results showed an excellent controlled pH-sensitive release profile. Cell apoptosis and in vitro cytotoxicity were investigated using flow cytometry and MTT analyses. CS/PAA/g-C3N4/CUR resulted in the highest rate of apoptosis in MCF-7 breast cancer cells, demonstrating the excellent nanocomposite efficacy in eliminating cancerous cells. CS/PAA hydrogel coated with g-C3N4 shows great potential for pH-sensitive controlled drug release.

Aptamer-functionalized quantum dots as theranostic nanotools against cancer and bacterial infections: A comprehensive overview of recent trends.

Aptamers (Apts) are synthetic nucleic acid ligands that can be engineered to target various molecules, including amino acids, proteins, and pharmaceuticals. Through a series of adsorption, recovery, and amplification steps, Apts are extracted from combinatorial libraries of synthesized nucleic acids. Using aptasensors in bioanalysis and biomedicine can be improved by combining them with nanomaterials. Moreover, Apt-associated nanomaterials, including liposomes, polymeric, dendrimers, carbon nanomaterials, silica, nanorods, magnetic NPs, and quantum dots (QDs), have been widely used as promising nanotools in biomedicine. Following surface modifications and conjugation with appropriate functional groups, these nanomaterials can be successfully used in aptasensing. Advanced biological assays can use Apts immobilized on QD surfaces through physical interaction and chemical bonding. Accordingly, modern QD aptasensing platforms rely on interactions between QDs, Apts, and targets to detect them. QD-Apt conjugates can be used to directly detect prostate, ovarian, colorectal, and lung cancers or simultaneously detect biomarkers associated with these malignancies. Tenascin-C, mucin 1, prostate-specific antigen, prostate-specific membrane antigen, nucleolin, growth factors, and exosomes are among the cancer biomarkers that can be sensitively detected using such bioconjugates. Furthermore, Apt-conjugated QDs have shown great potential for controlling bacterial infections such as Bacillus thuringiensis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Campylobacter jejuni, Staphylococcus aureus, and Salmonella typhimurium. This comprehensive review discusses recent advancements in the design of QD-Apt bioconjugates and their applications in cancer and bacterial theranostics.

Carboxymethyl cellulose/starch/reduced graphene oxide composite as a pH-sensitive nanocarrier for curcumin drug delivery.

Nanocomposites are promising drug carriers to treat terminal cancers with few adverse effects. Herein, nanocomposite hydrogels composed of carboxymethyl cellulose (CMC)/starch/reduced graphene oxide (RGO) were synthesized via a green chemistry approach and then encapsulated in double nanoemulsions to act as pH-responsive delivery systems for curcumin, a potential antitumor drug. A water/oil/water nanoemulsion containing bitter almond oil served as a membrane surrounding the nanocarrier to control drug release. DLS and zeta potential measurements were used to estimate the size and confirm the stability of curcumin-loaded nanocarriers. The intermolecular interactions, crystalline structure and morphology of the nanocarriers were analyzed through FTIR spectroscopy, XRD and FESEM, respectively. The drug loading and entrapment efficiencies were significantly improved compared to previously reported curcumin delivery systems. In vitro release experiments demonstrated the pH-responsiveness of the nanocarriers and the faster curcumin release at a lower pH. The MTT assay revealed the increased toxicity of the nanocomposites against MCF-7 cancer cells compared to CMC, CMC/RGO or free curcumin. Apoptosis was detected in MCF-7 cells via flow cytometry tests. The results obtained herein support that the developed nanocarriers are stable, uniform and effective delivery systems for a sustained and pH-sensitive curcumin release.

Biopolymer Composites 2022.

Recently, sustainable, biodegradable, and nontoxic materials, especially from renewable resources, have gained a lot of attention, and an important effort has been put into the research of biodegradable and biocompatible polymers as an alternative to petroleum-based commodity plastics [...].

Electrochemical nanobiosensor based on reduced graphene oxide and gold nanoparticles for ultrasensitive detection of microRNA-128.

Acute lymphoblastic leukemia (ALL) is one of the most prevalent cancers in children and microRNA-128 is amongst the most useful biomarkers not only for diagnosis of ALL, but also for discriminating ALL from acute myeloid leukemia (AML). In this study, a novel electrochemical nanobiosensor based on reduced graphene oxide (RGO) and gold nanoparticles (AuNPs) has been fabricated to detect miRNA-128. Cyclic Voltametery (CV), Square Wave Voltametery (SWV) and Electrochemical Impedance Spectroscopy (EIS) have been applied to characterize the nanobiosensor. Hexacyanoferrate as a label-free and methylene blue as a labeling material were used in the design of the nanobiosensors. It was found that the modified electrode has excellent selectivity and sensitivity to miR-128, with a limit of detection of 0.08761 fM in label-free and 0.00956 fM in labeling assay. Additionally, the examination of real serum samples of ALL and AML patients and control cases confirms that the designed nanobiosensor has the potential to detect and discriminate these two cancers and the control samples.

Biomedical applications of aptamer-modified chitosan nanomaterials: An updated review.

Among polysaccharides of environmental and economic interest, chitosan (CS) is receiving much attention, particularly in the food and biotechnology industries to encapsulate active food ingredients and immobilize enzymes. CS nanoparticles (CS NPs) combine the intrinsic beneficial properties of both natural polymers and nanoscale particles such as quantum size effect, biocompatibility, biodegradability, and ease of modification, possessing enhanced capacity for bioimaging, drug delivery, and biosensing applications. Aptamers are single-stranded oligonucleotides that can fold into predetermined structures and bind to the corresponding biomolecules. They are mainly used as targeting ligands in biosensors, disease diagnostic kits, and treatment strategies. They can deliver contrast agents and drugs into cancer cells and tissues, control microorganism growth, and also precisely target pathogens. Aptamer-conjugated CS NPs can significantly improve the efficacy of conventional therapies, minimize their side effects on normal tissues, and overcome the enhanced permeability retention (EPR) effect. Further, aptamer-conjugated carbohydrate-based nanobiopolymers have shown excellent antibacterial and antiviral properties and can be used to develop novel biosensors for the efficient detection of antibiotics, toxins, and other biomolecules. This updated review aims to provide a comprehensive overview of the bioapplications of aptamer-conjugated CS NPs used as innovative diagnostic and therapeutic platforms, their limitations, and potential future directions.

Novel carboxymethyl cellulose-halloysite-polyethylene glycol nanocomposite for improved 5-FU delivery.

Drug nano-carriers are crucial for achieving targeted treatment against cancer disorders with minimal side effects. In this study, a pH-responsive nanocomposite based on halloysite nanotube (HNT) coated with carboxymethyl cellulose (CMC)/polyethylene glycol (PEG) hydrogel for controlled delivery of 5-Fluorouracil (5-FU), a hydrophobic chemotherapy drug prescribed for different types of cancers was synthesized for the first time using the water-in-oil-in-water (W/O/W) technique. The developed CMC/PEG/HNT/5-FU nanocomposite was characterized by dynamic light scattering (DLS), zeta potential, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Field emission scanning electron microscope (FE-SEM) to get information about the particle size, surface charge, interactions between functional groups, crystalline structure and morphology, respectively. High efficiencies in terms of drug entrapment and loading (46 % and 87 %, respectively) were attained. In-vitro drug release results revealed an improved and sustained 5-FU delivery in an acid environment compared to the physiological medium, corroborating the pH-sensitivity of the developed nano-carrier. Flow cytometry and MTT assays demonstrated that the 5-FU loaded nanocomposite had considerable cytotoxicity on MCF-7 breast cancer cells while it is not toxic against L929 fibroblast cells. The nanocomposite synthesized herein could serve as a platform for the pH-sensitive release of anti-cancer drugs.

Fabrication and in vitro evaluation of chitosan-gelatin based aceclofenac loaded scaffold.

Scaffold development is a nascent field in drug development. The scaffolds mimic the innate microenvironment of the body. The goal of this study was to formulate a biocompatible and biodegradable scaffold, loaded with an analgesic drug, aceclofenac (Ace). The bioscaffold is aimed to have optimum mechanical strength and rheology, with drug released in a sustained manner. It was prepared via chemical cross-linking method: a chitosan (CS) solution was prepared and loaded with Ace; gelatin (GEL) was added and the mixture was cross-linked to get a hydrogel. 20 formulations were prepared to optimize different parameters including the stirring speed, drug injection rate and crosslinker volume. The optimal formulation was selected based on the viscosity, drug solubility, homogeneity, porosity and swelling index. A very high porosity and swelling index were attained. In vitro release data showed sustained drug delivery, with effective release at physiological and slightly acidic pH. SEM analysis revealed a homogeneous microstructure with highly interconnected pores within an extended polymer matrix. FT-IR spectra confirmed the absence of polymer-drug interactions, XRD provided evidences for efficient drug entrapment within the scaffold. Rheological analysis corroborated the scaffold injectability. Mathematical models were applied to in-vitro data, and the best fit was attained with Korsmeyer-Peppas.

5-Fluorouracil nano-delivery systems as a cutting-edge for cancer therapy.

5-Fluorouracil (5-FU) is amongst the most commonly used antimetabolite chemotherapeutic agents in recent decades. However, its low bioavailability, short half-life, rapid metabolism and the development of drug resistance after chemotherapy limit its therapeutic efficiency. In this study, 5-FU applications as an anti-cancer drug for treating diverse types of cancers (e.g. colon, pancreatic and breast) have been reviewed. Different approaches lately designed to circumvent the drawbacks of 5-FU therapy are described herein, including 5-FU-loaded lipid-based nanoparticles (NPs), polymeric NPs (both stimuli and non-stimuli responsive), carbon-based nanostructures and inorganic NPs. Furthermore, co-delivery systems of 5-FU with other drugs (e.g. paclitaxel, gelatin-doxorubicin and naproxen) have been reviewed, which aid to attain better bioavailability, higher effectiveness at a lower concentration and lower toxicity. This review provides researchers with the latest progress on 5-FU-loaded nanocarriers, which show great potential as an advanced tool for cancer therapy.

Emulgel-loaded mannosylated thiolated chitosan-coated silver nanoparticles for the treatment of cutaneous leishmaniasis.

Topical treatment of cutaneous leishmaniasis holds great promise for decreasing drug associated side effects and improving efficacy. This study was aimed to develop mannosylated thiolated chitosan-coated silver nanoparticles (MTCAg) loaded emulgel for the treatment of cutaneous leishmaniasis. MTC-Ag were synthesized via a chemical reduction method and were loaded into the emulgel. The nanoparticles had a zeta potential of +19.8 mV, an average particle size of 115 nm and a narrow polydispersity index of 0.26. In-vitro release profiles showed controlled release of silver ions from both the MTC-Ag and the emulgel-loaded MTC-Ag nanoparticles after 24 h. An ex-vivo retention study indicated 5 times higher retention of silver by the emulgel-loaded MTC-Ag than by the MTC-Ag nanoparticles. The in-vitro anti-leishmanial assay revealed that MTC-Ag had an excellent inhibitory effect on intracellular amastigotes, leading to ~90 % inhibition at the highest concentration tested. A 4-fold reduction in the IC50 value was found for MTC-Ag compared to blank Ag nanoparticles. Cytotoxicity assay showed 83 % viability of macrophages for MTC-Ag and 30 % for Ag nanoparticles at a concentration of 80 µg/mL, demonstrating the improved biocompatibility of the polymeric nanoparticles. Drug release and retention studies corroborate the great potential of MTC-Ag-loaded emulgel for the treatment of cutaneous leishmaniasis.