Bactericidal, anti-biofilm, anti-oxidant potency and catalytic property of silver nanoparticles embedded into functionalised chitosan gel.

Chitosan is a versatile biocompatible polysaccharide which has attracted great attention for gel synthesis. Its reducing character is specifically exploited for nanoparticle synthesis via green approach. A silver nanocomposite synthesized using this gel, with a novel gelling agent 2,4,6-trihydroxy benzaldehyde, was found to be a promising candidate for several applications including anti-bacterial, anti-biofilm and anti-oxidant activity as well as catalysis. The nanocomposite was well characterized using various spectroscopic and microscopic techniques such as IR, TGA, XRD, XPS, SEM and TEM. The nanocomposite exhibited high bactericidal activity against both S. aureus and E. coli. Further, it was evaluated for anti-biofilm forming property and its potency as antioxidant agent. The nanocomposite served as a catalyst for degradation of Methyl Orange and Rhodamine B at high concentrations (in the range of mM) with a catalytic efficiency of 98.58 % and 99.56 % within 3 min and 5 min respectively.

Functionalization of hyaluronic acid for development of self-healing hydrogels for biomedical applications: A review.

Materials that are capable of undergoing self-repair following any physical damage or rupture due to external stimuli are identified as self-healing materials. Such materials are engineered by crosslinking the polymer backbone chains typically through reversible linkages. These reversible linkages include imines, metal-ligand coordination, polyelectrolyte interaction, disulfide, etc. These bonds are reversibly responsive to changes in various stimuli. Newer self-healing materials are now being developed in the field of biomedicine. Chitosan, cellulose, starch etc. are a few examples of polysaccharides that are generally used to synthesize such materials. Hyaluronic acid has been a very recent addition to the list of polysaccharides that are being investigated for construction of self-healing materials. It is non-toxic, non-immunogenic, has good gelation property and good injectability. Hyaluronic acid based self-healing materials are particularly employed for targeted drug delivery, protein and cell delivery, electronics, biosensors and many such biomedical applications. This review critically focuses on the functionalization of hyaluronic acid to fabricate self-healing hydrogels for biomedical applications. It also explores and sums up the mechanical data as well as self-healing efficiency of the hydrogels across wide range of interactions as discussed in the review below.

Palladium nanoparticles-confined pore-engineered urethane-linked thiol-functionalized covalent organic frameworks: a high-performance catalyst for the Suzuki Miyaura cross-coupling reaction.

Covalent organic frameworks (COFs) are potential templates for the synthesis of nanomaterials owing to the versatility of their structure. Most of the reported COFs comprise imine linkages. Herein, we report for the first time the synthesis of a urethane-linked COF (UCOF) using monoformylphloroglucinol and 1,4-phenylene diisocyanate as monomers. Furthermore, the UCOF was functionalized with cysteamine to introduce free dangling thiol groups into the cavity. The latter played a critical role in fixing the active metal efficiently and facilitating the confined growth of small metal nanoparticles (∼4-6 nm) with a high surface area leading to a pore-engineered heterogeneous Pd catalyst (PdNPs@UCOF-SH). The COF and Pd catalyst were characterized using various analytical techniques such as CP-MAS NMR, FTIR, PXRD, BET, FEG-SEM, HRTEM, XPS, TGA, and ICP-AES. The as-prepared UCOF-SH-supported Pd nanoparticles showed excellent catalytic activity in the Suzuki Miyaura cross-coupling reaction under mild conditions with low catalyst loading and eco-friendly solvents. The scope was extended to various aryl boronic acids and aryl halides (I, Br, and Cl). The halo-substituted and non-halo biaryl derivatives were obtained in good to excellent yields, within a shorter reaction time, avoiding the homocoupling of aryl boronic acid. The pore-engineered COF-derived catalyst is selective and easily recycled up to 10 runs without significant loss of catalytic activity. This reveals the robust nature of the PdNPs@UCOF-SH catalyst and the sustainability of the process which opens a new frontier for several catalytic applications.

α-Hydroxy acids modified ß-cyclodextrin capped iron nanocatalyst for rapid reduction of nitroaromatics: A sonochemical approach.

This study reports a sonochemical approach for the synthesis and catalytic performance of zerovalent iron nanoparticles (nZVI) capped with two cyclodextrin (CD) crosslinked polymers derived from Lactic acid and Citric acid (CDLA and CDCA respectively). The polymers and the catalysts were characterized by NMR, FTIR, HRTEM, DLS, Zeta potential, FESEM, EDAX, VSM, XRD, XPS, TGA analysis. The catalysts proved to be sustainable and recyclable for rapid sonochemical reduction of nitroaromatics under ambient conditions. The isolated yield of the derivatives was found to be greater than 90%. The results suggest excellent dispersibility, stability, high iron content and smaller size of CDLA polymer capped nZVI compared to CDCA capped nZVI, leading to two-fold higher catalytic activity. The effect of various crucial catalysis parameters was investigated and optimized. The scope of the reaction was extended to other nitroaromatics under the optimized conditions. Being magnetically separable, the cost effective and non-toxic catalysts exhibited high recycling efficiency (~13 cycles), high turnover number (TON) and turnover frequency (TOF). The recyclable catalysts could be low-cost and sustainable options for organic transformation in water via sonochemical approach in aqueous medium.

Vitamin-H Channeled Self-Therapeutic P-gp Inhibitor Curcumin-Derived Nanomicelles for Targeting the Tumor Milieu by pH- and Enzyme-Triggered Hierarchical Disassembly.

An effective nanocarrier-mediated drug delivery to cancer cells primarily faces limitations like the presence of successive drug delivery barriers, insufficient circulation time, drug leakage, and decreased tumor penetration capacity. With the aim of addressing this paradox, a self-therapeutic, curcumin-derived copolymer was synthesized by conjugation with PEGylated biotin via enzyme- and acid-labile ester and acetal linkages. This copolymer is a prodrug of curcumin and self-assembles into ∼150-200 nm-sized nanomicelles; it is capable of encapsulating doxorubicin (DOX) and hence can be designated as self-therapeutic. pH- and enzyme-responsive linkages in the polymer skeleton assist in its hierarchical disassembly only in the tumor microenvironment. Further, the conjugation of biotin and poly(ethylene glycol) (PEG) imparts features of tumor specificity and improved circulation times to the nanocarrier. The dynamic light scattering (DLS) analysis supports this claim and demonstrates rapid swelling and disruption of micelles under acidic pH. UV-vis spectroscopy provided evidence of an accelerated acetal degradation at pH 4.0 and 5.0. The in vitro release studies revealed a controlled release of DOX under acidic conditions and curcumin release in response to the enzyme. The value of the combination index calculated on HepG2 cells was found to be <1, and hence, the drug pair curcumin and DOX acts synergistically for tumor regression. To prove the efficiency of acid-labile linkages and the prodrug strategy for effective cancer therapy, curcumin-derived polymers devoid of sensitive linkages were also prepared. The prodrug stimuli-responsive nanomicelles showed enhanced cell cytotoxicity and tumor penetration capability on HepG2 cells as well as drug-resistant MCF-7 cell lines and no effect on normal NIH/3T3 fibroblasts as compared to the nonresponsive micelles. The results were also supported by in vivo evidence on a hepatocellular carcinoma (HCC)-induced nude mice model. An evident decrease in MMP-2, MMP-9, and α-fetoprotein (AFP), the biomarkers specific to tumor progression, was observed along with metastasis upon treatment with the drug-loaded dual-responsive nanomicelles. These observations corroborated with the SGOT and SGPT data as well as the histoarchitecture of the liver tissue in mice.

A review on remediation technologies using functionalized Cyclodextrin.

Modern lifestyle and alleviated anthropogenic activities have increased the pollutant load, ultimately causing stress on the environment. In industrialization, many harmful compounds are released into the environment polluting air, water, and soil, triggering adverse impacts on the ecosystem and human beings. Therefore, the development of advanced remediation technologies turns out as a significant environmental priority. Less polar cyclic oligosaccharide Cyclodextrin (CD) with cavity binding organic compounds attracted attention by helping effectively as environmental application. The formation of inclusion complexes and modified Cyclodextrin by cross-linking or surface modification enhances their capacity to abate pollutant effectively from the environment. Modification results in the formation of several novel materials such as CD-based composites, nanocomposites, crosslinked polymer or hydrogels, potent cross-linkers, CD-based membranes, and CD immobilized supports. Several environmental remediation technologies based on Cyclodextrin and modified Cyclodextrin have been discussed in detail in this review. Various environmental applications of Cyclodextrin and its derivatives have been discussed, along with their formation, properties, and characterization. Effective removal of organic pollutants, inorganic pollutants, micropollutants, volatile compounds etc., has been explained using several remediation technologies. Based on CD innocuity, this is referred to as the green process. The reversible equilibrium corresponded by the inclusion phenomenon sets a significant trend in the field of CD environmental application to develop techniques by incorporating supramolecular chemistry as well as irreversible methods such as biodegradation and advanced oxidation. It helps in the complete removal of pollutants and ultimately recycling the CD.

Emerging hybrid biomaterials for oxidative stress induced photodynamic therapy.

Cancer therapy has undergone tremendous advancements in the past few years. The drawbacks of most of these therapies have encouraged researchers to obtain further insight into the complex chemical, biochemical and biological processes ongoing in the evolving cancer cells. These studies have led to an advent of reactive oxygen species mediated therapies to target and disrupt the cancer pathology. Photodynamic therapy (PDT) has emerged as a potent candidate for oxidative stress mediated non-invasive technique for rapid diagnosis and treatment of cancer. Towards this, biomacromolecules derived hybrid nanomaterials have contributed largely in the development of various therapeutics and theranostics for efficacious cancer management that can assist PDT. This review summarizes various hybrid biomaterials and advanced techniques that have been explored widely in the past few years for PDT application. The article also mentions some of the important in-vitro and in-vivo developments and observations explored by employing these materials for PDT application. The article also describes the interactions of these materials at the biological interface and the probable mechanism that assist in generation of oxidative stress and subsequent cell death.

Carbon nanotube embedded cyclodextrin polymer derived injectable nanocarrier: A multiple faceted platform for stimulation of multi-drug resistance reversal.

A combination of cocktail chemotherapy (CCT), photothermal therapy (PTT) and inhibition of angiogenesis was investigated as an effective approach to combat major challenges of multidrug resistance and non-targeted drug delivery encountered in conventional cancer therapy. An injectable nanocarrier was developed through functionalization of carbon nanotubes (CNTs) with rationally modified carbohydrate (ß-Cyclodextrin-CD) derived pH and thermo responsive polymer. Embedding CNT to CD polymer offers a nanocarrier which effectively demonstrated CCT, high NIR triggered photothermal efficiency, anti-angiogenic potential for selective tumor homing as well as enhanced multi-drug resistance (MDR) reversal with minimal toxic effects on normal cells. The simultaneously loading with curcumin and doxorubicin hydrochloride exhibited synergistic effect for triggering antitumor effect in vitro and demonstrated down regulation of growth factors associated with angiogenesis ex-ovo. In-vivo studies ascertained that the nanocarrier synthesized with the rational for MDR reversal can lead to enhanced cancer cell death via multiple approaches.

Maleic Anhydride Cross-Linked ß-Cyclodextrin-Conjugated Magnetic Nanoadsorbent: An Ecofriendly Approach for Simultaneous Adsorption of Hydrophilic and Hydrophobic Dyes.

A magnetic nanoadsorbent with a cross-linked ß-Cyclodextrin maleic anhydride polymer capable of simultaneous removal of hydrophilic and hydrophobic dyes was developed with high efficacy and desorption/recycling efficiency. The effect of various parameters (concentration, adsorbent dosage, contact time, pH, and temperature) was evaluated to assess the optimum adsorption conditions. The superparamagnetic nanoadsorbent (SPNA) could be easily separated by magnetic decantation and showed maximum removal of malachite green with 97.2% adsorption efficiency. Studies on simultaneous adsorption of dyes from a mixture were performed and the adsorption capacity was calculated. Interestingly, the phenomenon of competitive adsorption was observed. The adsorption process can be fitted well into the Langmuir isotherm model and follows pseudo-second-order kinetics. SPNA could be effectively regenerated and recycled at least five times without any significant loss in removal efficiency. SPNA could be an ideal adsorbent for water remediation because of excellent dye removal efficiency in addition to chemical stability, ease of synthesis, and better reusability.

Toxicity evaluation of magnetic iron oxide nanoparticles reveals neuronal loss in chicken embryo.

Magnetic iron oxide nanoparticles (IONs) display the ability to cross blood - brain barrier and are envisioned as diagnostic and therapeutic applications, but there are few studies on their potential embryonic toxicity in higher vertebrates. This study investigates interaction of IONs with egg albumen and its subsequent toxicity on chicken embryo. Physicochemical interactions of IONs with egg albumen revealed alterations in friccohesity and secondary structural changes due to weak Vander Waals forces. Toxicity assessment of IONs (10, 25, 50, 100, and 200 µg/ml doses) on chicken embryo accounted for 100% mortality at 200 µg/ml dose due to Fe2+ ions overload. However, lower doses (50 and 100 µg/ml) recorded decrement in whole weights and crown-rump lengths of chicken embryo possibly due to ION-albumen interactions. Histology of brain tissue revealed degeneration of neurons (50-60%) at 10-100 µg/ml dose range of IONs. Toxicity studies of IONs with diverse animal models are needed to set a toxicity benchmark for preventing embryonic toxicity prior to its use in biomedical applications. This is the first study on toxicity assessment of IONs in chicken embryo.

ß-cyclodextrin based dual-responsive multifunctional nanotheranostics for cancer cell targeting and dual drug delivery.

Multifunctional nanoconjugates possessing an assortment of key functionalities such as magnetism, florescence, cell-targeting, pH and thermo-responsive features were developed for dual drug delivery. The novelty lies in careful conjugation of each of the functionality with magnetic Fe3O4 nanoparticles by virtue of urethane linkages instead of silica in a simple one pot synthesis. Further ß-cyclodextrin (CD) was utilized to carry hydrophobic as well as hydrophilic drug. Superlative release of DOX could be obtained under acidic pH conditions and elevated temperature, which coincides with the tumor microenvironment. Mathematical modelling studies revealed that the drug release kinetics followed diffusion mechanism for both hydrophobic drug and hydrophilic drug. A number of fluorophores onto a single nanoparticle produced a strong fluorescence signal to optically track the nanoconjugates. Enhanced internalization due to folate specificity could be observed by fluorescence imaging. Further their accumulation driven by magnet near tumor site led to magnetic hyperthermia. in vitro studies confirmed the nontoxicity and hemocompatibility of the nanoconjugates. Remarkable cell death was observed with drug-loaded nanoconjugates at very low concentrations in cancer cells. The internalization and cellular uptake of poor bioavailable anticancer agent curcumin were found to be remarkably enhanced on dosing the drug loaded nanoconjugates as compared to free curcumin. Site specific drug delivery due to folate conjugation and subsequent significant suppression in tumor growth was demonstrated by in vivo studies.

TiO2 nanoparticles induce omphalocele in chicken embryo by disrupting Wnt signaling pathway.

Titanium dioxide nanoparticles (TiO2 NPs) are among abundantly used metal oxide NPs but their interactions with biomolecules and subsequent embryonic toxicity in higher vertebrates is not extensively reported. Physicochemical interactions of TiO2 NPs with egg albumen reveals that lower doses of TiO2 NPs (10 and 25 µg/ml) accounted for higher friccohesity and activation energy but an increment in molecular radii was recorded at higher doses (50 and 100 µg/ml). FTIR analysis revealed conformational changes in secondary structure of egg albumen as a result of electrostratic interactions between egg albumen and TiO2 NPs. The morphometric data of chicken embryo recorded a reduction at all the doses of TiO2 NPs, but toxicity and developmental deformity (omphalocele and flexed limbs) were recorded at lower doses only. Inductively coupled plasma optical emission spectrometry (ICP-OES) confirmed presence of Ti in chicken embryos. mRNA levels of genes involved in canonical and non-canonical Wnt signaling were lowered following TiO2 NPs treatment resulting in free radical mediated disruption of lateral plate mesoderm and somite myogenesis. Conformational changes in egg albumen and subsequent developmental deformity in chicken embryo following TiO2 NPs treatment warrants detailed studies of NP toxicity at lower doses prior to their biomedical applications.

A review on carbohydrate embedded polyurethanes: An emerging area in the scope of biomedical applications.

Polyurethanes (PUs) are expanding to newer horizons in the field of biomedical sciences, particularly due to their exceptional set of properties that deem fit for applications in the said field. On the other hand, carbohydrates find increasing attention as components of biomedical devices due to their easy availability from renewable resources. The manipulation of PUs by carbohydrate has solved the major concern of biodegradability, biocompatibility and economy. This review summarizes the recent trends in PUs embedded with carbohydrates ranging from monosaccharide to polysaccharides, including supramolecular host such as cyclodextrin etc. Diverse approaches for embedding them in PUs in various forms have been listed. In recent decade, significant research has been carried out to employ such polymers in biomedical applications such as drug delivery devices, implants, scaffolds for tissue engineering etc. This knowledge could facilitate the selection of more efficient approach for synthesis of polymeric systems based on the biological macromolecules.

Cellulose crosslinked pH-responsive polyurethanes for drug delivery: α-hydroxy acids as drug release modifiers.

Cellulose crosslinked waterborne polyurethanes (PUs) based on poly ɛ-caprolactone with lactic acid/glycolic acid/dimethylol-propionic acid as a drug release modifiers cum chain extenders were prepared. PUs were loaded with felodipine and drug release was monitored at different pH values. The structure of the polymers was characterized by FTIR, DSC & TGA and SEM. The encapsulation of dug inside PU matrix and the morphology of polymer after drug release were studied by using SEM. All the PUs were observed to degrade under highly basic conditions. The PUs act as pH sensitive drug carriers with an added advantage of modulated release rate as a function of acid chain extenders. The rate of release of the drug was significantly faster at pH 7.4 as compared to gastric pH 1.2, with same incubation time. The PUs reported in the present study may be suitable for medical applications like vaginal drug delivery and colon specific drug delivery.

Sunflower oil mediated biomimetic synthesis and cytotoxicity of monodisperse hexagonal silver nanoparticles.

In this work, sunflower oil was utilized for the biomimetic synthesis of silver (Ag) nanoparticles (NPs), leading to highly mono-dispersed hexagonal-shaped silver nanoparticles (NPs) at various concentrations. It was found that the biomolecules of the oil not only have the capability to reduce silver ions, due to its extended phenolic system, but also appear to recognize and affect the Ag nanocrystal growth on the (110) face, leading to hexagonal growth of the NPs of 50 nm size. Initially, some spherical AgNPs of less than 10nm diameter were observed; however, over a longer period of time, a majority of hexagonal-shaped nanocrystals were formed. The one step synthesis can be extended for other metals. The as prepared sunflower oil capped AgNPs being completely free of toxic chemicals can be directly utilized for in vitro studies and offer a more rational approach for cellular applications. The NP solution exhibited dose-dependent cytotoxicity in human lung carcinoma cells and physiologically relevant cell model (3T3L1 cells).

Structure-property relationships and biocompatibility of carbohydrate crosslinked polyurethanes.

Biocompatible and biodegradable polyurethanes (PUs) based on castor oil and polypropylene glycols (PPGs) were prepared using various carbohydrate crosslinkers: monosaccharide (glucose), disaccharide (sucrose) and polysaccharides (starch and cellulose). The mechanical and thermal properties were investigated and interpreted on the basis of SEM study. The advantage of incorporating various carbohydrates is to have tunable mechanical properties and biodegradability due to variety in their structure. The glass transition temperature and sorption behavior were dominated by the type of polyol than by the type of crosslinker. All the PUs were observed to be biodegradable as well as non-cytotoxic as revealed by MTT assay in normal lung cell line L132. The study supports the suitability of carbohydrates as important components of biocompatible PUs for development of biomedical devices.

Synthesis and cytotoxicity evaluation of novel acylated starch nanoparticles.

Starch nanoparticles (StNPs) were acylated under ambient conditions to obtain various nanosized derivatives formed stable suspension in water and soluble in organic solvents. The degree of substitution (DS) was determined using (1)H NMR technique. The cytotoxicity potential of the derivatised StNPs was evaluated in mouse embryonic fibroblast (3T3L1) cells and A549 tumor cell line using MTT cell viability assay. Other parameters that determine the oxidative stress viz., reactive oxygen species (ROS) generation, intracellular reduced glutathione (GSH), superoxide generation and acridine orange/ethidium bromide staining were also investigated. The present study led to the conclusion that cytotoxic activity of acylated starch nanoparticles was dependent on their dosage, DS and type of substitution. The non-toxic nature in non-cancerous cells reveals that the nanoparticles (NPs) can be used for cancer therapy and drug delivery. The nanoparticles also offered reasonable binding propensity with CT-DNA.

Cytotoxicity evaluation and antimicrobial studies of starch capped water soluble copper nanoparticles.

Water soluble monodisperse copper nanoparticles of about 10nm diameter were prepared by microwave irradiation using starch as green capping agent. The resulting Cu-starch conjugate were characterized by FTIR and energy dispersive X-ray analysis (EDX). The study confirmed the presence of copper embedded in polysaccharide matrix. The aqueous solution of starch capped copper nanoparticles (SCuNPs) exhibited excellent bactericidal action against both gram negative and gram positive bacteria. The in vitro cytotoxicity evaluation of the nanoparticles was carried out using mouse embryonic fibroblast (3T3L1) cells by MTT cell viability assay, extracellular lactate dehydrogenase (LDH) release and dark field microscopy imaging. The capped nanoparticles exhibited cytotoxicity at much higher concentration compared to cupric ions. Minimum bactericidal concentration (MBC) of SCuNPs was well below the in vitro cytotoxic concentration. Statistical analysis demonstrated p<0.05 for significant results and p>0.05 for non-significant ones as compared to untreated cells. The non-cytotoxic green Cu-starch conjugate offers a rational approach towards antimicrobial application and for integration to biomedical devices.

Oxidative stress induced apoptosis of human lung carcinoma (A549) cells by a novel copper nanorod formulation.

This study elucidates the process of synthesis of copper (Cu) nanorods using almond skin extract as stabilizing cum capping agent. These nanorods were (about 200 nm long and 40 nm wide) characterized by transmission electron microscopy (TEM). Further, cytotoxicity potential of these nanorods was evaluated in A549 cells (Human lung carcinoma cell line) via cell viability assay and extracellular lactate dehydrogenase (LDH) release. Also, reduced glutathione (GSH), lipid peroxidation (LPO), cellular oxidative stress (Rhodamine 123 florescence) and apoptosis (Annexin V FITC/Propidium iodide staining) were also investigated in control and treated cells. Results indicated that Cu nanorods induced apoptotic death of cancer cells by induction of oxidative stress, depletion of cellular antioxidants and mitochondrial dysfunction. This study reports a novel process of synthesis of almond skin extract capped Cu nanorods and its potential as an anticancer agent against A549 lung carcinoma cells.

Isocyanate crosslinked reactive starch nanoparticles for thermo-responsive conducting applications.

Hydrophobic nanoparticles and nanocomposite films of 1,4-hexamethylene diisocyanate (HMDI)-modified starch nanoparticles (SNPs) have been synthesized at ambient temperatures. The platelet-like starch nanocrystals become pseudospherical after modification with HMDI and the size increases or decreases depending on diisocyanate concentration compared to the ungrafted particles as revealed by transmission electron microscopy (TEM) results. The obtained nanocrystals were characterized by means of the FT-IR and X-ray diffraction (XRD) techniques. When compared with the hydrophobic performance of the unmodified starch nanocrystals, that of crosslinked starch nanocrystals significantly increased. X-ray diffraction reveals that the crystalline structure of modified starch nanocrystals was preserved. The resulting hydrophobic starch nanoparticles are versatile precursors to the development of nanocomposites. The polyether-polyurethane crosslinked with SNPs nanocomposite film exhibited thermo-responsive electrical conductivity.