Alginate templated synthesis, characterization and in vitro osteogenic evaluation of strontium-substituted hydroxyapatite.

The objective of this study is to explore the potential role of alginate (Alg) in the crystallization of metal-substituted hydroxyapatite, with application in orthopaedic reconstruction. The alginate at different concentrations (0.5 and 1.0 wt%) facilitated in situ mineralization of hydroxyapatite (HA) and strontium-substituted HA (SHA, 10 and 30 mol%). The incorporation of the biopolymer and dopant induced notable changes in HA, including reduced crystal size from 31.0 to 16.4 nm and increased lattice volume from 577.3 to 598.0 Å3. The superior affinity of alginate for Sr2+ than for Ca2+ resulted in higher residual alginate in Alg/SHA (13.0 to 19.0 %) compared to Alg/HA (7.1 to 8.2 %). This residual alginate influenced composite properties: surface charge decreased from -26.5 to -45.7 mV, microhardness increased from 0.33 to 0.54 GPa, and dissolution increased from 0.17 to 0.39 %. The in vitro studies revealed that strontium substitution as well as the organization and crystallographic aspects of apatite regulated osteoblastic cell survival, proliferation, differentiation, and biomineralization. The findings suggest that an alginate concentration of 0.5 wt% is optimal for the crystallization of SHA with 10 mol% substitution, and its resulting composite possesses the ideal biomechanical properties to imitate native bone.

Dextrose, maltose and starch guide crystallization of strontium-substituted hydroxyapatite: A comparative study for bone tissue engineering application.

The influence of carbohydrates on the crystallization of metal-substituted hydroxyapatite predicts its relevance to natural bone growth. This study demonstrates the role of carbohydrates in the crystallization of strontium-substituted hydroxyapatite (SHAP). The increasing order of hydroxyl groups, dextrose (monosaccharide) < maltose (disaccharide) < starch (polysaccharide), coordinated with Ca2+/Sr2+ and thus guided SHAP crystallization, with crystal size reduced from 35 to 19 nm, lattice volume increased from 518 to 537 Å3, and residual carbohydrates increased from 1.8 to 20.2 %. The variation in residual carbohydrates is due to their interaction with apatite and/or aqueous insolubility. Compared to pure SHAP, the starch-SHAP with higher residual starch showed increased water uptake from 1.23 ± 0.18 to 4.26 ± 0.21 % and degradation from 0.22 ± 0.06 to 1.53 ± 0.14 %, but decreased microhardness from 0.73 ± 0.12 to 0.38 ± 0.01 GPa and protein affinity from 4.82 ± 0.01 to 0.81 ± 0.01 µg/mg. However, its microhardness value was bone-like, and the reduced protein adsorption was masked by the rich osteogenic behaviour. In vitro cellular response demonstrated that the residual carbohydrate and strontium augmented osteocompatibility, proliferation, differentiation and biomineralization. The result concludes that carbohydrates drive SHAP crystallization, and starch-SHAP replicates natural bone.

Effect of pectin on the crystallization of strontium substituted HA for bone reconstruction application.

The biomacropolymers of bone extracellular matrix (ECM) guide the growth of hydroxyapatite (HA) with various ionic substitutions. Pectin, a plant polysaccharide with chemical similarities to ECM, was investigated for its potential to promote the crystallization of strontium-substituted HA (SH). The influence of pectin (0.5 and 1.0 wt%) on the in situ mineralization of SH (10 and 30 mol% calcium substitution with strontium) was studied. The preferential affinity of pectin to strontium over calcium favoured the incorporation of strontium in apatite, decreased crystal size (18.85-26.22 nm) and retained more pectin residues (8-16%). The residual pectin strongly interacted with small SH particles, resulting in high microhardness (0.43-0.85 GPa) and high surface charge (-32.1 to -30.3 mV), while weak interaction with large HA particles resulted in low microhardness (0.15-0.25 GPa) and low surface charge (-35.4 to -34.6 mV). The in vitro cellular study using human osteoblast-like MG-63 cells demonstrated that inorganic size and material crystallinity play a vital role in regulating osteogenesis. The study suggests that the synchronization of low pectin concentration (0.5 wt%) and high strontium substitution in HA (30 mol%) offers the desired microhardness and in vitro osteogenic properties to emulate natural bone.

Development of a quaternary ammonium poly (amidoamine) dendrimer-based drug carrier for the solubility enhancement and sustained release of furosemide.

Furosemide (FRSD) is a loop diuretic that has been categorized as a class IV drug according to the Biopharmaceutics Classification System (BCS). It is used in the treatment of congestive heart failure and edema. Owing to low solubility and permeability, its oral bioavailability is very poor. In this study, two types of poly (amidoamine) dendrimer-based drug carriers (generation G2 and G3) were synthesized to increase the bioavailability of FRSD through solubility enhancement and sustained release. The developed dendrimers enhanced the solubility of FRSD 58- and 109-fold, respectively, compared with pure FRSD. In vitro studies demonstrated that the maximum time taken to release 95% of the drug from G2 and G3 was 420-510 min, respectively, whereas for pure FRSD the maximum time was only 90 min. Such a delayed release is strong evidence for sustained drug release. Cytotoxicity studies using Vero and HBL 100 cell lines through an MTT assay revealed increased cell viability, indicating reduced cytotoxicity and improved bioavailability. Therefore, the present dendrimer-based drug carriers are proven to be prominent, benign, biocompatible, and efficient for poorly soluble drugs, such as FRSD. Therefore, they could be convenient choices for real-time applications of drug delivery.

Graphene oxide reinforced SrHAP composite as a drug carrier in bone regeneration.

Strontium substituted HAP (SrHAP), with a 10 mol% substitution, was mineralized on increasing weight percentages of graphene oxide (2, 4 and 6). The GS composites were comprehensively characterized for drug delivery in bone reconstruction. The formation of SrHAP was verified by XRD and FT-IR results. The apatite crystallization was influenced by graphene oxide content and strontium. The EDS results confirmed the presence of strontium and HR-SEM depicted rod shape apatite, of length between 58 and 135 nm, uniformly embedded on graphene oxide. The reinforcement of graphene oxide increased the surface area, porosity, microhardness (upto 0.59 GPa), protein adsorption (upto 18.16 µg/mg), water uptake and degradation properties. Also, the increase in graphene oxide fraction significantly enhanced the curcumin encapsulation efficiency (upto 80.16%) and the drug release was considerably retarded over SrHAP. The in vitro studies using human osteoblast-like MG-63 cells demonstrated that curcumin-loaded composite was biocompatible and promoted proliferation, differentiation and matrix mineralization. The results highlight the combinational therapy of osteogenic ion (strontium) and osteogenic drug (curcumin) as a promising platform in bone tissue engineering.

Evaluation of quaternization effect on chitosan-HAP composite for bone tissue engineering application.

This study attempts to improve the aqueous solubility of chitosan and utilizes it in the fabrication of composites with hydroxyapatite (HAP). The composites were evaluated as a curcumin delivery vehicle for bone regeneration. The chitosan was modified by quaternization, with a quaternization degree of 5 % for low quaternized chitosan (LQC) and 11 % for high quaternized chitosan (HQC). The modified chitosan, at alkaline pH 11, facilitated in situ HAP growth and formed LQC-HAP and HQC-HAP composites. The quaternization weakens intermolecular hydrogen bonds, facilitates interaction with the apatite precursor ions and promotes the growth of HAP. The modification significantly improved drug encapsulation (2.6 fold) but at the cost of a slight decrease in mechanical strength and increase in drug release. The in vitro studies with human osteoblast-like MG-63 cells established that the curcumin-loaded composites, LQC-HAP-C and HQC-HAP-C are biocompatible, encourage proliferation and promote a 2-fold increase in calcium mineralization over drug-free composites. The study exemplifies the reciprocity between quaternization degree and drug load/release properties and also illustrates that the magnitude of the latter reflects bioactivity. Thus, the quaternized chitosan-based HAP composite with tailorable bio-physicochemical properties becomes an interesting drug delivery system in bone regeneration.

Size controlled silver nanoparticles on ß-cyclodextrin/graphitic carbon nitride: an excellent nanohybrid material for SERS and catalytic applications.

A nanohybrid (NH), having high dispersion of silver nanoparticles (AgNPs) on ß-cyclodextrin (ß-CD)/graphitic carbon nitride (g-CN), designated as AgNPs/ß-CD/g-CN-NH, was synthesized and characterized. It was exploited for a couple of environmental remediation applications like SERS sensing and catalytic reduction of specific organic pollutants in water. It showed excellent SERS activity as a Raman probe for the detection of malachite green (MG). Its enhancement factor (EF) and detection limit for MG were equal to 7.26 × 106 and 1 × 10-9 M, respectively. The relative standard deviation (RSD) was equal to 3.8% which indicates high homogeneity of AgNP dispersion and signal reproducibility of the SERS substrate. The NH displayed high catalytic activity for the reduction of eosin yellow (EY) in the presence of NaBH4 with the rate constant (k) of 0.1142 min-1. A comparison of the present NH with other reported materials reveals better SERS and catalytic activities of the former than those of the latter. The SERS activity of the NH was also examined for sensing of other triphenylamine dyes like methyl violet (MV), and it was successful. The same NH also exhibited high catalytic activity towards the reduction of Congo red (CR). The results of both studies clarify that the NH is an excellent SERS substrate and efficient catalyst for the detection of organic environmental pollutants having structures similar to MG and their degradation. This is due to the distribution of the controlled size of AgNPs on g-CN promoted by ß-CD. Therefore, we focus our attention on future environmental applications of the nanohybrid as a very cheap SERS substrate and a very active catalyst.

Silver nanoparticles decorated g-C3N4: An efficient SERS substrate for monitoring catalytic reduction and selective Hg2+ions detection.

Graphitic carbon nitride supported Ag NPs(AgNPs@g-C3N4) were synthesized by an in-situ chemical reduction using a green reducing agent, tannic acid. They were characterized by UV-Vis, FTIR, XPS, XRD, FESEM, EDAX and HRTEM. They were very much SERS sensitive, and capable of detecting methylene blue and 4-aminothiophenol at 1 × 10-12 M and 1 × 10-10 M, respectively with the corresponding SERS enhancement factor of 1.4 × 108 and 4.7 × 107. Apart from its high SERS sensitivity, it exhibited high catalytic activity for the reduction of MB with NaBH4. So, their SERS activity and catalytic activity were combined successfully to monitor catalytic reduction of MB by SERS technique. Further, the SERS activity towards MB was also employed for the detection/quantification of free Hg2+ ions in aqueous solution. The SERS intensity of MB drastically decreased in the presence of Hg2+ ions, and hence it provides novel route to detect and quantify the latter. Presence of Ca2+, Mg2+, Cu2+ and Cd2+ions showed zero interference for it. So, this study proves that Ag NPs@g-C3N4 as a unique substrate for multiple SERS applications.

Facile synthesis of core-shell nanocomposites Au catalysts towards abatement of environmental pollutant Rhodamine B.

Magnetically recoverable Au nanoparticles immobilized/stabilized on core-shell nanocomposites are synthesized by the combination of suspension polymerization as well as surface initiator atom transfer radical polymerization (SI-ATRP) methods. The magnetic core-shell supported Au nanocatalysts are namely Fe3O4-PAC-AuNPs, Fe3O4-PVBC-g-PAC-AuNPs, Fe3O4-HEA-AuNPs, and Fe3O4-PVBC-g-HEA-AuNPs. Among all the catalysts, Fe3O4-PVBC-g-PAC-Au NPs exhibited an excellent activity in the reduction of Rhodamine B with an apparent rate constant of 10.77 × 10-3 s-1 and TOF value of 47.62 × 10-3 s-1 under pseudo-first order reaction condition. Further, Fe3O4-PVBC-g-PAC-Au NPs has an outstanding activity and recyclability without applying any external magnetic field. This new approach provides an exciting potential way in the preparation of recyclable metal nano-catalysts with high catalytic activity.

Drug delivery investigations of quaternised poly(propylene imine) dendrimer using nimesulide as a model drug.

This study describes the demonstration of quaternized poly(propylene imine) dendrimer of generation-3, QPPI (G3) as a drug carrier for poorly soluble drug nimesulide (NMD, an anti-inflammatory drug). QPPI (G3) was prepared by treating the surface amine groups of poly(propylene imine) dendrimer with glycidyltrimethyl ammonium chloride and it was characterized with FTIR, (1)H and (13)C NMR and MALDI-TOF mass spectral techniques. The drug carrying potential of QPPI (G3) was assessed by analyzing drug solubility, in vitro release and cytotoxicity studies. The observed results reveal that the aqueous solubility of NMD has been dramatically increased in the presence of QPPI (G3) and also can sustain the release of NMD. It is further noticed that the complexation of NMD with QPPI (G3) is responsible for increased solubility and sustained release. This complexation was evidenced through NMR ((1)H & 2D) and UV-vis spectral techniques, DSC and DLS studies. Cytotoxicity study through MTT assay on Vero and HBL-100 cell lines reveal that this dendrimer increase the biocompatibility and the tolerance concentration of NMD in drug-dendrimer formulations. The observed results prove that the QPPI (G3) is one of the new promising candidate for effective delivery of NMD.

Synthesis, characterization, and catalytic activity for hybrids of multi-walled carbon nanotube and amphiphilic poly(propyleneimine) dendrimer immobilized with silver and palladium nanoparticle.

Four types of new multi-walled carbon nanotube (MWCNT) based nanohybrid catalysts were prepared through simple methods. Initially, MWCNT was functionalized with carboxyl group and subsequently bonded with amphiphilic poly(propyleneimine) dendrimer (APPI) having generation (G2) and (G3). They are abbreviated as MWCNT-APPI (G2) and MWCNT-APPI (G3). Silver nanoparticles (AgNPs) and palladium nanoparticles (PdNPs) were separately immobilized to each hybrid to obtain four types of MWCNT based nanohybrid catalysts. The pseudo-first order rate constants for reduction of 4-nitrophenol revealed that among the four types of MWCNT nanohybrid catalysts, MWCNT-APPI (G3)-PdNPs was more efficient than the other catalysts with five-fold higher efficiency than the homogeneous PPI (G3)-PdNPs. For the same reaction with MWCNTs-APPI (G3)-PdNPs catalyst, the variation of [catalyst] and [NaBH4] was directly proportional to kobs. The study of reusability of MWCNT-APPI (G3)-PdNPs proved no loss in activity even after recycling the catalyst for five times.

Effective functionalization of multiwalled carbon nanotube with amphiphilic poly(propyleneimine) dendrimer carrying silver nanoparticles for better dispersability and antimicrobial activity.

Two multiwalled carbon nanotube hybrids have been prepared: (a) multiwalled carbon nanotubes (MWCNTs) functionalized with amphiphilic poly(propyleneimine) dendrimer (APPI), viz. MWCNTs-APPI, and (b) silver nanoparticles (AgNPs)-deposited multiwalled carbon nanotubes functionalized with an amphiphilic poly(propyleneimine) dendrimer (MWCNTs-APPI-AgNPs). The degree of covalent functionalization of APPI in MWCNTs and deposition of AgNPs in MWCNTs-APPI were examined by Fourier transform infrared spectroscopy, zeta potential, scanning and high-resolution transmission electron microscopy, energy-dispersive spectroscopy, thermogravimetric analysis, and Raman spectroscopy. The amount of APPI functionalized on MWCNTs determined by thermal gravimetric analysis was about 67% which enables an effective dispersability in aqueous and organic solvents without sonication and these solutions were stable for 6 months without undergoing aggregation of MWCNTs. The electronic properties of the hybrid materials were not altered drastically as verified by the Raman studies. The antimicrobial activities of MWCNTs-APPI and MWCNTs-APPI-AgNPs against three different bacteria, viz. Bacillus subtilis, Staphylococcus aureus, and Escheriachia coli illustrated excellent activity.

A novel steroid from Elephantopus scaber L. an ethnomedicinal plant with antidiabetic activity.

Acetone extract of Elephantopus scaber, an ethnomedicnal plant, reduced the blood glucose levels in streptozotocin-induced diabetic rats significantly. Acute toxicity studies revealed the non-toxic nature of the crude extract. Fractionation of the acetone extract yielded a new steroid, 28Nor-22(R)Witha 2,6,23-trienolide. Biological testing of the compound demonstrated a significant antidiabetic activity by reducing the elevated blood glucose levels and restoring the insulin levels in streptozotocin-induced diabetic rats. This compound can be a useful candidate to treat diabetes.