Thermoresponsive lipids engineered magnetic nanoparticles for spatiotemporal delivery of hesperidin to inflammatory sites in animal model.

Thermoresponsive nanoparticles are exploited as drug-delivery vehicles that release their payload upon increment in temperature. We prepared and characterized thermoresponsive lipid-anchored folic acid engineered magnetic nanoparticles (LP-HP-FANPs) that combine receptor-based targeting and thermoresponsive sustained release of hesperidin (HP) in response to endogenous inflammation site temperature. The progressive surface engineering of NPs was validated by FTIR analysis. Our LP-HP-FANPs had a particle size of 100.5 ± 1.76 nm and a zeta potential of 14.6 ± 2.65 mV. The HP encapsulation effectiveness of LP-HP-FANPs is around 91 ± 0.78%. AFM scans indicated that our modified nanoparticles were spherical. LP-HP-FANPs exhibit increased drug release (85.8% at pH 4.0, 50.9% at pH 7.0) at 40 °C. Animal studies showed no toxicity from nanoparticles. Compared to conventional drugs and HP, LP-HP-FANPs effectively decreased paw edema, cytokine levels, and total cell recruitment in thioglycollate-induced peritonitis (p < 0.05). LP-HP-FANPs substantially decreased cytokines compared to HP, HP-FA-NPs, and the standard medication (p < 0.05, p < 0.01, and p < 0.001). These findings imply that the synthesized HP-loaded formulation (LP-HP-FANPs) may be a potential anti-inflammatory formulation for clinical development.

Highly functionalized pH-triggered supramolecular nanovalve for targeted cancer chemotherapy.

Chemotherapeutic drug delivery systems are commonly limited by their short half-lives, poor bioavailability, and unsuccessful targetability. Herein, pH-responsive hybrid NPs consist of benzimidazole-coated mesoporous silica nanoparticles (BZ-MSN) loaded with naturally occurring flavonoid quercetin (QUE-BZ-MSN). The NPs were further capped with beta-cyclodextrin (BCD) to obtain our desired BCD-QUE-BZMSN, with a zeta potential around 7.05 ± 2.37 mV and diameter about 115.2 ± 19.02 nm. The abundance of BZ onto the nanoparticles facilitates targeted quercetin chemotherapy against model lung and liver cancer cell lines. FTIR, EDX, and NMR analyses revealed evidence of possible surface functionalizations. Powder XRD analysis showed that our designed BCD-QUE-BZMSN formulation is amorphous in nature. The UV and SEM showed that our designed BCD-QUE-BZMSN has high drug entrapment efficiency and a nearly spherical morphology. In vitro, drug release assessments show controlled pH-dependent release profiles that could enhance the targeted chemotherapeutic response against mildly acidic regions in cancer cell lines. The obtained BCD-QUE-BZMSN nanovalve achieved significantly higher cytotoxic efficacy as compared to QUE alone, which was evaluated by in vitro cellular uptake against liver and lung cancer cell lines, and the cellular morphological ablation was further confirmed via inverted microscopy. The outcomes of the study imply that our designed BCD-QUE-BZMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Targeted pH-responsive delivery of rosmarinic acid via phenylboronic acid functionalized mesoporous silica nanoparticles for liver and lung cancer therapy.

Currently, chemotherapy is one of the most practiced approaches for the treatment of cancers. However, existing chemotherapeutic drugs have poor aqueous solubility, poor selectivity, higher systematic toxicity, and poor target accumulation. In this study, we designed and synthesized a boronic acid/ester-based pH-responsive nano-valve that specifically targets the microenvironment in cancer cells. The nano-valve comprises phenylboronic acid-coated mesoporous silica nanoparticles (B-MSN) loaded with polyphenolic compound Rosmarinic acid (ROS-B-MSN). The nano-valve was further coated with lignin (LIG) to achieve our desired LIG-ROS-BMSN nano-valve for targeted chemotherapy against Hep-G2 and NCI-H460 cell lines. The structure and properties of NPs were characterized by Fourier-transformed infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM) in combination with EDX, and Dynamic light scattering (DLS). The outcomes revealed that the designed LIG-ROS-BMSN were in the nanorange (144.1 ± 0.70 nm), had negative Zeta potential (-15.7 ± 0.46 mV) and had a nearly spherical morphology. In vitro, drug release investigations showed a controlled pH-dependent release profile under mild acidic conditions that could enhance the targeted chemotherapeutic response against cancer in mild acidic environments. The obtained LIG-ROS-BMSN nano valve achieved significantly lower IC50 values of (1.70 ± 0.01 µg/mL and 3.25 ± 0.14 µg/mL) against Hep-G2 and NCI-H460 cell lines as compared to ROS alone, which was (14.0 ± 0.7 µg/mL and 29.10 ± 0.25 µg/mL), respectively. The cellular morphology before and after treatment was further confirmed via inverted microscopy. The outcomes of the current study imply that our designed LIG-ROS-BMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Synthesis and characterization of honey based hybrid dental implants with enhanced antibacterial activity.

Dental implants are commonly used for tooth replacement tools due to their good oral rehabilitation and reconstruction capacities. Dental implants treatment for natural teeth is desired to achieve successful implants treatment with improved osseointegration through promotion of mammalian cell activity and prevention of bacterial activity. Honey is potentially known for its antimicrobial and antibacterial potential, specifically for burns and wound healing. In this study, honey based silver nanoparticles were synthesized using various concentrations of honey. The synthesized HNY-AgNPs, MSN and HNY-AgMSN were characterized for their surface Plasmon resonance using UV spectroscopy, Hydrodynamic diameter using Zetasizer. Morphology using AFM. Furthermore, surface functional groups were characterized using FTIR spectroscopy at 4cm-1 resolutions. The developed hybrid nanoparticles were tested for their anti-bacterial activity at concentration of 3000µg/mL. It was found HNY-AgNPs was active against both bacterial strains i.e, Streptococcus mutans and streptococcus aureus. HNY-AgNPs-MSN hybrid implant demonstrated potential new type of dental implants, which can offer an effective design for the fabrication of advanced dental implants.

Beneficial Effects of Trillium govanianum Rhizomes in Pain and Inflammation.

Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC50, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation.

Atomic force microscopic imaging of Acanthamoeba castellanii and Balamuthia mandrillaris trophozoites and cysts.

Light microscopy and electron microscopy have been successfully used in the study of microbes, as well as free-living protists. Unlike light microscopy, which enables us to observe living organisms or the electron microscope which provides a two-dimensional image, atomic force microscopy provides a three-dimensional surface profile. Here, we observed two free-living amoebae, Acanthamoeba castellanii and Balamuthia mandrillaris under the phase contrast inverted microscope, transmission electron microscope and atomic force microscope. Although light microscopy was of lower magnification, it revealed functional biology of live amoebae such as motility and osmoregulation using contractile vacuoles of the trophozoite stage, but it is of limited value in defining the cyst stage. In contrast, transmission electron microscopy showed significantly greater magnification and resolution to reveal the ultra-structural features of trophozoites and cysts including intracellular organelles and cyst wall characteristics but it only produced a snapshot in time of a dead amoeba cell. Atomic force microscopy produced three-dimensional images providing detailed topographic description of shape and surface, phase imaging measuring boundary stiffness, and amplitude measurements including width, height and length of A. castellanii and B. mandrillaris trophozoites and cysts. These results demonstrate the importance of the application of various microscopic methods in the biological and structural characterization of the whole cell, ultra-structural features, as well as surface components and cytoskeleton of protist pathogens.

Structural dynamics and anti-biofilm screening of novel imidazole derivative to explore their anti-biofilm inhibition mechanism against Pseudomonas Aeruginosa.

The biofilm formation is still prevalent mechanism of developing the drug resistance in the Pseudomonas aeruginosa, gram-negative bacteria, known for its major role in nosocomial, ventilator-associated pneumonia (VAP), lung infections and catheter-associated urinary tract infections. As best of our knowledge, current study first time reports the most potent inhibitors of LasR, a transcriptional activator of biofilm and virulence regulating genes in, Pseudomonas aeruginosa LasR, utilizing newly functionalized imidazoles (5a-d), synthesized via 1,3-dipolar cycloaddition using click approach. The synthesized ligands were characterized through Mass Spectrometry and 1H NMR. The binding potency and mode of biding of ligands. Quantum Mechanical(QM) methods were utilized to investigate the electronic basis, HOMO/LUMO and dipole moment of the geometry of the ligands for their binding potency. Dynamics cross correlation matrix (DCCMs) and protein surface analysis were further utilized to explore the structural dynamics of the protein. Free energy of binding of ligands and protein were further estimated using Molecular Mechanical Energies with the Poisson-Boltzmann surface area (MMPBSA) method. Molecular Docking studies revealed significant negative binding energies (5a - 10.33, 5b -10.09, 5c - 10.11, and 5d -8.33 KJ/mol). HOMO/LUMO and potential energy surface map estimation showed the ligands(5a) with lower energy gaps and larger dipole moments had relatively larger binding potency. The significant change in the structural dynamics of LasR protein due to complex formation with newlyfunctionalized imidazoles ligands. Hydrogen bond surface analysis followed by MMPBSA calculations of free energy of binding further complemented the Molecular docking revelations showing the specifically ligand (5a) having the relatively higher energy of binding(-65.22kj/mol).Communicated by Ramaswamy H. Sarma.

Highly selective, sensitive and simpler colorimetric sensor for Fe2+ detection based on biosynthesized gold nanoparticles.

Herein, we describe the fabrication of green bell pepper, Capsicum annuum L. extract capped gold nanoparticles (CA-AuNPs) in aqueous medium using tetrachloroaurate (HAuCl4·3H2O) as precursor salt and sodium hydroxide (NaOH) solution as accelerator as well as pH adjuster. Formation of CA-AuNPs was verified via colour change from yellowish to ruby red with further confirmation through surface plasmon resonance (SPR) band at 519 nm using ultraviolet violet-visible (UV-Vis) spectroscopy. Other characterizations techniques include, Fourier transform infra-red (FTIR) spectroscopy, atomic force microscopy (AFM), dynamic light scattering (DLS) with Zeta-potential analysis (ZPA) and X-ray diffraction (XRD) method. The resulting AuNPs were efficaciously implemented as highly sensitive colorimetric sensor for selective detection of Fe2+ in the presence of several interfering cations including Fe3+. Importantly, the fabricated CA-AuNPs based colorimetric sensor functioned linearly in the range of 0.3-7.0 ppb Fe2+, based on increasing absorption intensity with R2 value of 0.9938 using UV-Vis spectrometry. The limit of detection (LOD) and limit of quantification (LOQ) for Fe2+ were estimated as 0.036 and 0.12 ppb, respectively. Finally, the sensor was effectively tested for determination of Fe2+ in some locally collected real water samples.

2-(4-Chloro-phen-yl)-4-[1-(4-chloro-phen-yl)-3-methyl-1H-pyrazol-5-yl]-5-methyl-1H-pyrazol-3(2H)-one.

The title compound, C(20)H(16)Cl(2)N(4)O, has two mol-ecules in the asymmetric unit. The two five-membered rings form a dihedral angle of 54.2 (3)° in one mol-ecule and 56.8 (3)° in the other independent mol-ecule. The amino group of the dihydro-pyrazolone unit of one mol-ecule acts as a hydrogen-bond donor to the carbonyl group of the dihydro-pyrazolone system of the other mol-ecule. The resulting N-H⋯O hydrogen bonds generate a chain running along the c axis. The crystal selected was a pseudo-merohedral twin with a 44.9 (3)% twin component.

4,4'-(Propane-1,3-diyldi-oxy)dibenz-aldehyde.

The title compound, C(17)H(16)O(4), is a dialdehyde in which two formyl-phen-oxy units are linked by a -CH(2)CH(2)CH(2)- chain; the mol-ecule is V-shaped with the middle methyl-ene C atom as the apex. The two benzene rings are aligned at 77.4 (1)°. In the crystal, mol-ecules are linked into centrosymmetric dimers by pairs of non-classical C-H⋯O hydrogen bonds.

9,9-Bis[4-(prop-2-yn-yloxy)phen-yl]-9H-fluorene.

In the title compound, C(31)H(22)O(2), the bond angle at the C atom belonging to the five-membered ring of the fluorene system is opened to 112.64 (12)°. The two benzene rings are twisted with respect to the fluorene ring system at dihedral angles of 72.81 (6) and 81.83 (6)°. One C(ar-yl)-O-C-C  fragment is extended, with a C-O-C-C torsion angle of -178.77 (13)°, but the other C(ar-yl)-O-C-C  fragment is bent, with a C-O-C-C torsion angle of 64.78 (19)°. Inter-molecular weak C-H⋯O hydrogen bonding is present in the crystal structure.

Propane-1,3-diyl bis-(4-amino-benzoate).

Mol-ecules of the title compound, C(17)H(18)N(2)O(4), lie on a twofold rotation axis that passes through the central methyl-ene C atom. The mol-ecules adopt a 'V' shape and the trimethyl-ene unit assumes a gauche-gauche conformation. The amino N atom shows a nonplanar coordination. Adjacent mol-ecules are connected by N-H⋯O hydrogen bonds into chains running along [001]. Furthermore, N-H⋯N hydrogen bonds connect these chains into a three-dimensional network.

(Butane-1,3-diyne-1,4-diyl)bis-(tri-isopropyl-silane).

The mol-ecule of the title compound, C(22)H(42)Si(2), lies on a center of inversion, and the triisopropyl-silyl groups are staggered.

Di-tert-butyl 2,2'-[9H-fluorene-9,9-diylbis(p-phenyl-ene-oxy)]diacetate.

In the title mol-ecule, C(37)H(38)O(6), the non-fused C atom belonging to the five-membered ring of the fluorene system is connected to two p-phenyl-ene rings, the rings opening up the C(ar-yl)-C-C(ar-yl) angle to 113.1 (1)°. The four-atom -O-CH(2)-C(=O)-O- chain between the p-phenyl-ene ring and the tert-butyl group assumes a more regular W-shaped conformation for one substituent [O-C-C-C torsion angle = 171.9 (2)°] but a less regular W-shaped conformation for the other [torsion angle = 147.4 (2)°].

Di-tert-butyl 2,2'-[(biphenyl-4,4'-diyl)-dioxy]diacetate.

The complete molecule of the title compound, C(24)H(30)O(6), is generated by a crystallographic inversion centre. In the unique part of the mol-ecule, the four-atom -O-CH(2)-C(= O)-O- chain between the benzene ring and the tert-butyl group assumes a zigzag conformation [O-C-C-O torsion angle = -162.3 (1)°].

tert-Butyl 2-[4-(2-{4-[(tert-butoxycar-bonyl)methoxy]-3-methylphenyl}-2-propyl)-2-methylphenoxy]acetate.

In the mol-ecule of the title compound, C(29)H(40)O(6), the carbon atom belonging to the propyl chain is connected to two aromatic rings that open up the C(ar-yl)-C-C(ar-yl) angle to 111.5 (1)°. The four-atom -O-CH(2)-C(=O)-O- linkage between the aromatic ring and the tert-butyl group assumes a (-)anti-periplanar conformation for one substituent and a (-)syn-periplanar conformation for the other substituent; the O-C-C-O torsion angles are -173.7 (2) and -10.2 (3)°.

Ortho-rhom-bic modification of bis-[4-(3-pyridyl-methyl-idene-amino)-phen-yl]methane.

The title compound, C(25)H(20)N(4), is a disubstituted methane derivative having two pyridyl-methyl-ene-amino-phenyl arms, one of which is essentially rigid as all atoms lie on a plane (r.m.s. deviation = 0.074 Å), whereas the other is twisted [dihedral angle between the phenyl-ene and pyridyl rings = 51.1 (4)°]. The angle at the methyl-ene C atom is 113.2 (2)°.

9,9-Bis[4-(2-chloro-eth-oxy)phen-yl]-9H-fluorene.

The title compound, C(29)H(24)Cl(2)O(2), a fluorene derivative, features a C atom that is connected to four phenyl-ene rings, two of which are almost coplanar (r.m.s. deviation = 0.035 Å) as they belong to the fluorene system. The other two rings are aligned at angles of 67.5 (5) and 85.5 (5)° with respect to the pair. The O and Cl atoms of the -OCH(2)CH(2)Cl- units adopt a gauche conformation [torsion angles = 61.6 (6) and 66.6 (5)°].

Oleic Acid Coated Silver Nanoparticles Showed Better in Vitro Amoebicidal Effects against Naegleria fowleri than Amphotericin B.

Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis (PAM) which almost always results in death. N. fowleri is also known as "brain-eating amoeba" due to its literal infestation of the brain leading to an inflammatory response in the brain tissues. Currently, there is no single drug that is available to treat PAM, and most treatments are combinations of antifungal, anticancer, and anti-inflammatory drugs. Recently nanotechnology has gained attention in chemotherapeutic research converging on drug delivery, while oleic acid (OA) has shown positive effects on the human immune system and inflammatory processes. In continuation of our recent research in which we reported the effects of oleic acid conjugated with silver nanoparticles (OA-AgNPs) against free-living amoeba Acanthamoeba castellanii, in this report, we show their antiamoebic effects against N. fowleri. OA alone and its nanoconjugates were tested against the amoeba by using amoebicidal and host cell cytopathogenicity assays. Trypan blue exclusion assay was used to determine cell viability. The results revealed that OA-AgNPs exhibited significantly enhanced antiamoebic effects (P < 0.05) against N. fowleri as compared to OA alone. Evidently, lactate dehydrogenase release shows reduced N. fowleri-mediated host cell cytotoxicity. Based on our study, we anticipate that further studies on OA-AgNPs could potentially provide an alternative treatment of PAM.

Synthesis of biocompatible triazole based non-ionic surfactant and its vesicular drug delivery investigation.

Numerous nanotechnological approaches have been widely practiced to improve the bioavailability of less aqueous soluble drugs; phospholipid based vesicles (liposomes) being the most widely applied drug delivery system. However; due to stability issues, large scale production limitations, sterilization and long term storage problems; non-ionic surfactant based vesicles (niosomes) are considered their excellent counterparts. Niosomes are vesicles of non-ionic surfactants having the ability to carrying both hydrophilic and hydrophobic drugs in their inner aqueous or lipid bilayer compartments. In this research work, triazole based non-ionic surfactant (TBNIS) was synthesized and characterized by different spectroscopic techniques and then screened for biocompatibility using NIH 3T3 cell line, blood hemolysis assay and acute toxicity in mice. The synthesized surfactant was then checked for niosomes' formation, Amphotericin B loading and entrapment efficiency, drug release, stability and bioavailability of the drug was assessed and compared with free drug solution. The synthesized surfactant was found biocompatible and caused less blood hemolysis, greater cell vial ability and negligible toxicity in animals. The size of drug loaded niosomal vesicles of TBNIS based surfactant was 179.9 ± 3.23 nm with smaller size distribution i.e. 0.29 ± 0.02. The triazole based surfactant vesicles showed 88.76 ± 3.45 % drug entrapment efficiency, sustained drug release profile and stability. The drug in TBNIS based vesicles has greater oral bioavailability 0.099 ± 0.03 as compared to plan drug solution 0.012 ± 0.023 µg/mL. Results of this study suggests that the newly synthesized triazole based surfactant can be used in drug delivery for improving bioavailability of less water soluble drugs like Amphotericin B.