Clarithromycin-Loaded Submicron-Sized Carriers: Pharmacokinetics and Pharmacodynamic Evaluation.

The current study aims to improve clarithromycin bioavailability and effectiveness in complicated intra-abdominal infection management. Therefore, clarithromycin-loaded submicron dual lipid carriers (CLA-DLCs) were developed via hot high shear homogenization technique and evaluated for colloidal parameters, release behavior, stability study, and in-vitro antibiofilm activity. Bioavailability and therapeutic efficacy of optimized formulation on hampering cytokines storm induction was determined in E. coli-induced peritonitis. The developed CLA-DLCs (particle size 326.19 ± 24.14 nm, zeta potential -31.34 ± 2.81 mV, and entrapment efficiency 85.78 ± 4.01%) exhibited smooth spherical shapes and sustained in vitro release profiles. Long-term stability study of optimized CLA-DLCs ensured maintenance of colloidal parameters for 1 year at room temperature. In vitro antimicrobial studies revealed 3.43-fold higher anti-biofilm activity of CLA-DLCs compared with clarithromycin. In addition, the relative bioavailability of CLA-DLCs was enhanced 5.89-fold compared to pure drug in rats. The remarkable decrease in microbial burden in blood as well as tissues, along with oxidative stress markers (lipid peroxidation, myeloperoxidase activity, and carbonylated protein level) and immunological markers (total leukocyte count, neutrophil migration, NO, TNF-, and IL-6) on treatment with CLA-DLCs enhanced the survival in a rat model of peritonitis compared with the pure drug and untreated groups. In conclusion, CLA-DLCs hold promising potential in management of intra-abdominal infections and prevention of associated complications.

Water-soluble PEG segmented mannose-based macromolecules: Synthesis, characterization and their biocompatibility.

The macromolecular architectures, namely mannose-based methacrylate acetyl-mannopyranoside and PEG block copolymers [AB type copolymer [PEG-b-PMAM], poly(ethyleneglycol)-b-poly(methacryl-2,3,4,6-tetra-O-acetyl-D-mannopyranoside) and ABA type copolymer [PMAM-b-PEG-b-PMAM], poly(methacryl-2,3,4,6-tetra-O-acetyl-D-mannopyranoside)-b-poly(ethyleneglycol)-b-poly(methacryl-2,3,4,6-tetra-O-acetyl-D-mannopyranoside)] were synthesized by atom transfer radical polymerization (ATRP) method that were deacetylated to generate the corresponding water-soluble and biocompatible glycopolymer macromolecules. The molecular weight of acetyl and deacetylate macromolecules was in the range of 7083-9499 and 4659-6026, as determined by GPC and proton NMR spectra. The 5 % decomposition temperatures for acetylated methacrylate macromolecules (218-299 °C) were higher than the corresponding water-soluble macromolecules (204-248 °C). The conjugation of poly(methacryl-2,3,4,6-tetra-O-acetyl-D-mannopyranoside) (PMAM) segment with the PEG block decreased the glass transition (Tg) value, and the water-soluble macromolecules displayed Tg in the range of 92-95 °C. The biocompatibility of the synthesized water-soluble mannose-based macromolecules was determined using Human Bone Derived Cells (HBDC) culture with the TCP (Tissue culture plastic) template as control. Using three different concentrations of the synthesized glycopolymers, HBDC's were cultured for 1, 3, and 7 days. The effect of mannomethacrylate macromolecules on mitochondrial activity of HBDC's was estimated using colorimetry that showed the conversion of MTS [3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide] to formazan (MTS assay). ABA type diblock copolymer architecture exhibited increased absorbance values of 3 and 7 day cultures at 1-100 M concentrations, with the highest values observed at a concentration of 1 M for day 3 cultures. The design of these novel mannose-based macromolecules is important for improving cell proliferation, cell adhesion, and osteointegration efficiency.

A facile one pot synthesis of novel pyrimidine derivatives of 1,5-benzodiazepines via domino reaction and their antibacterial evaluation.

A new series of pyrimidine (8, 14, 18 and 23) embellished analogues of 1,5-benzodiazepines were synthesized by the one-pot domino approach using the catalyst DABCO (1,4-diazabicyclo[2.2.2]octane). For each compound synthesized, anti-microbial efficacy was determined using broth microdilution assay and half maximal inhibitory concentration (IC50). Furthermore, FESEM (Field emission scanning electron microscope) studies were also carried out to observe the effect of the structure of test compounds on the morphology of both Gram-positive (S. aureus) and Gram-negative (E. coli) cell walls. The leakage of nucleotides and their integral components from compromised bacterial cells was assessed by plotting the optical density (OD) with respect to time of exposure at 320 nm. Anti-bacterial studies revealed that compound 23 was most active against targeted bacterial species. Results of the antibacterial study indicated that all the test compounds possess significant antibacterial potential against targeted bacterial strains. Amongst all, in the FE-SEM study, compound 23 caused marked alteration in bacterial cell morphology and resulted in maximum leakage of cell nucleotides in bacterial strains as compared to controls. Further efforts are required to establish their efficacy as antibacterial agents in clinical management.

Preparation of electrospun PCL-based scaffolds by mono/multi-functionalized GO.

In the present study, sythetic biodegradable polymer poly(ε-caprolactone) (PCL) and graphene oxide (GO) were combined together to prepare 3D, composite tissue scaffolds (PCL/GO scaffolds) by using electrospinning technique. Also, the influence of Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) and/or thiophene (Th) modified GO on the composite PCL/GO mats (PCL/GO, PCL/GO-GRGDSP, PCL/GO-Th, PCL/GO-GRGDSP-Th) was further investigated. Characteristic examinations of the scaffolds were carried out by scanning electron microscope (SEM), contact angle (CA) measurements, x-ray photoelectron spectroscopy, TGA, electrical conductivity tests, phosphate buffer saline absorption and shrinkage tests and mechanical tests. All of the scaffolds were exhibited suitable bead-free and uniform morphology according to SEM images. With the addition of GO, better hydrophilicity and a slight CA decrease (∼5°) for the PCL/GO scaffolds were observed. Mechanical properties were reinforced drastically with the addition and well-dispersion of GO into PCL matrix. The incorporation of PCL and GO exhibited enhanced electrical conductivity and the highest value was found for PCL/GO-GRGDSP-Th (2%) as 15.06 µS cm-1. The MG-63 osteoblast cell culture studies (MTT assay, ALP activity, Alizarin-Red staining, fluorescence and SEM analyses) showed that PCL/GO-GRGDSP-Th (1%) scaffolds exhibited the highest biocompatibility performance (1.87 fold MTT absorbance value comparing with neat PCL) due to the advanced properties of GO and the biological interfaces.

Flurbiprofen-loaded ethanolic liposome particles for biomedical applications.

Present study deals with the preparation, characterization and in-vivo evaluation of flurbiprofen loaded ethanolic liposome which provides predetermined and controlled release of drug through a transdermal drug delivery system. Ethanolic liposomes were prepared by using flurbiprofen, phospholipon 90-G, and ethanol in varied concentration ratio. The prepared ethanolic liposomes were optimized and characterized for particle size, zeta potential, polydispersive index and % entrapment efficiency. FTIR study was performed to analyze the interaction between drug and excipient. To study the thermal behavior of the formulation DSC and TGA were carried out. The surface morphology of ethanolic liposome was performed with the help of SEM, TEM, and AFM. In-vitro drug permeation study of the optimized formulation was carried out using the albino rat skin model and peripheral nociceptive activity was evaluated by writhing assay. In addition, formulations were also inspected for stability study for three months at a different temperature. The optimized formulation EF5 exhibited a particle size of 167.2 ±â€¯3.7 nm with a zeta potential of -51.6 ±â€¯0.2 mV and PDI of 0.209. The optimized formulation showed an ideal surface morphology with a maximum % entrapment efficiency i.e. 93.51 ±â€¯2.1. In-vitro permeation study shows a release of 70.23% in 24 h and transdermal flux was found as 238.2 µg/cm2/h. Writhing assay demonstrate that the optimized formulation decreases the number of writhes and thus shows the peripheral analgesic activity. In stability study, optimized formulation showed maximum stability at 4 °C. These results suggest that transdermal system mediated application of flurbiprofen loaded ethanolic liposome can be considered as an effective way to afford consistent and predictable release of flurbiprofen which could provide beneficial effects in the management of various inflammatory diseases.

Lipid-polymer hybrid nanoparticles: Synthesis strategies and biomedical applications.

This review article is an updated overview on lipid-polymer hybrid nanoparticles (LPHNs) including the various types of LPHNs polymers used in their preparation, various methods of preparation, their physiochemical, in-vitro and in-vivo evaluation parameters and their application in various delivery systems. LPHNs show a combined advantage of biodegradable polymeric nanoparticles and liposomes. LPHNs mainly consist of a biodegradable polymeric material core containing drugs or any substances which are to be encapsulated then this core is further enclosed by a phospholipid layer i.e. lipid PEG layer. LPHNs show good physical strength and biocompatibility. The hybrid structural design can offer various benefits such as controlled particle size, high drug loading, surface functionality with various ligands (antibody fragments, peptides, monoclonal antibodies, aptamers, and folate molecules), and encapsulation of combinational therapeutic agents, showing prolonged release of drug and drug circulates in the blood for longer duration. Significantly, the LPHNs have recently been confirmed as a better drug delivery route and good cellular delivery efficacy of various drugs as compared to polymeric nanoparticles and liposomes.

Green synthesis and characterization of copper nanoparticles by Tinospora cardifolia to produce nature-friendly copper nano-coated fabric and their antimicrobial evaluation.

Metallic nanoparticles such as gold, zinc, copper possess anti-microbial activity. These nanoparticles have a small size which provides a large surface area for the interaction with microbes and there are various mechanisms through which copper nanoparticles (CuNPs) act. The demand of these nanoparticles are increasing in the textile industry as they decrease the catalytic degradation property of various dyes as well as being helpful in the treatment of various topical infections. Our aim is to formulate the copper nanoparticle which is capped with Tinospora cardifolia and incorporate these nanoparticles on fabric and to study the anti-microbial activity of these nanoparticles formulated along with their study on the fabric. Formulated nanoparticles were tested for various characterizations such as SEM (Scanning Electron Microscope), TEM (Transmission Electron Microscope) for the microscopical study. The interaction of excipients with the drug was studied using FTIR, XRD, and Raman and the anti-microbial study was studied to determine the activity of the nanoparticles on gram-positive and gram-negative bacteria. Least particle size of 63.3 nm was used as optimized formulation (CuNPs-5) and further used for testing. Laundry durability, ZOI study and %efficacy of copper nanoparticles along with nanoparticle-coated fabric was tested and it was found that fabric was more efficacious for gram-positive bacteria as ZOI for gram positive and gram negative was 21.99 mm and 11 mm. The %efficacy of copper nanoparticle-coated fabric was 101% and 74% at the highest concentration for gram positive and gram negative bacteria respectively.

Development of Poly(vinyl alcohol) (PVA)/Reduced Graphene Oxide (rGO) Electrospun Mats.

In this study, electrospun reduced graphene oxide (rGO) and poly(vinyl alcohol) (PVA) nanocomposites were developed with the concentration of rGO as 0.5 and 1.0 wt% by dispersing rGO in the PVA solution without using any co-solvent which may cause toxic effect for possible applications like packaging and tissue engineering. Water solubility of PVA was eliminated by UV-radiation crosslinking method. SEM analysis proved that continuous and bead-free nanofibers were obtained by electrospinning process and all electrospun mats had similar fiber characteristics with homogeneous fiber morphology. The average fiber diameter (nm), inter-fiber pore size (µm) and the porosity (%) were increased with rGO incorporation. Additionally, enhanced tensile properties was achieved by rGO addition as the highest tensile strength was obtained as ∼5 MPa for electrospun PVA + 1.0 wt% rGO nanocomposites. ATR-FTIR analyses showed that there was a relatively strong interfacial interaction between rGO and PVA. Moreover, the thermal stability of obtained nanocomposites was enhanced by rGO addition without changing the crystal structure of PVA proved by XRD analyses. Also, improved electrical conductivity of the nanocomposites was obtained by rGO content as the highest conductivity (∼11 µS · cm-1) was measured for electrospun PVA + 1.0 wt% rGO.

Polycaprolactone-thiophene-conjugated carbon nanotube meshes as scaffolds for cardiac progenitor cells.

The myocardium is unable to regenerate itself after infarct, resulting in scarring and thinning of the heart wall. Our objective was to develop a patch to buttress and bypass the scarred area, while allowing regeneration by incorporated cardiac stem/progenitor cells (CPCs). Polycaprolactone (PCL) was fabricated as both sheets by solvent casting, and fibrous meshes by electrospinning, as potential patches, to determine the role of topology in proliferation and phenotypic changes to the CPCs. Thiophene-conjugated carbon nanotubes (T-CNTs) were incorporated to enhance the mechanical strength. We showed that freshly isolated CPCs from murine hearts neither attached nor spread on the PCL sheets, both with and without T-CNT. As electrospun meshes, however, both PCL and PCL/T-CNT supported CPC adhesion, proliferation, and differentiation. The incorporation of T-CNT into PCL resulted in a significant increase in mechanical strength but no morphological changes to the meshes. In turn, proliferation, but not differentiation, of CPCs into cardiomyocytes was enhanced in T-CNT containing meshes. We have shown that changing the topology of PCL, a known hydrophobic material, dramatically altered its properties, in this case, allowing CPCs to survive and differentiate. With further development, PCL/T-CNT meshes or similar patches may become a viable strategy to aid restoration of the postmyocardial infarction myocardium.

The incorporation of mono- and bi-functionalized multiwall carbon nanotubes in organic photovoltaic cells.

We have successfully prepared mono- and bi-functionalized multiwall carbon nanotubes (MWCNT) with thiophene, amine and thiophene-amine groups. The dispersion of nanotubes has been enhanced and stable optimized dispersions in organic solvents were obtained. These functionalized nanotubes have been successfully incorporated into bulk heterojunction (BHJ) organic photovoltaic (OPV) cells with a poly (3-hexyl thiophene) (P3HT) and [6, 6]-phenyl-C(61)-butyric acid methyl ester (PCBM) photoactive blended layer. The incorporation of MWCNT with different functional groups, in the active layer, results in different cell performance with respect to a reference cell. A maximum power conversion efficiency of 2.5% is achieved with the inclusion of thiophene functionalized nanotubes. This improvement in the device performance is attributed to an extension of the exciton dissociation volume and charge transport properties through the nanotube percolation network in P3HT/CNT, PCBM/CNT or both phases. This is believed to be due to more efficient dispersion of the functionalized nanotubes within the photoactive composite layer.

Bifunctional, chemically patterned flat stamps for microcontact printing of polar inks.

Different methods to create chemically patterned, flat PDMS stamps with two different chemical functionalities were compared. The best method for making such stamps, functionalized with 1H,1H,2H,2H-perfluorodecyltrichlorosilane (PFDTS) and 3-(aminopropyl)triethoxysilane (APTS), appeared to be full functionalization of a freshly oxidized flat PDMS stamp with either adsorbate, followed by renewed oxidation through a mask and attachment of the other adsorbate. These stamps were used to transfer polar inks (a thioether-functionalized dendrimer and a fluorescent dye) by microcontact printing. The PFDTS monolayer was used as a barrier against ink transfer, while the APTS SAM areas functioned as an ink reservoir for polar inks. The printing results confirmed the excellent transfer of hydrophilic inks with these stamps to gold and glass substrates, even from aqueous solutions. Attachment of a fluorescent dye on the amino-functionalized regions shows the possibility of the further modification of the chemically patterned stamps for tailoring of the stamps' properties.

Surface modification of elastomeric stamps for microcontact printing of polar inks.

Chemical modification of the surface of a stamp used for microcontact printing (microCP) is interesting for controling the surface properties, such as the hydrophilicity. To print polar inks, plasma polymerization of allylamine (PPAA) was employed to render the surface of poly(dimethylsiloxane) (PDMS), polyolefin plastomers (POP), and Kraton elatomeric stamps hydrophilic for long periods of time. A thin PPAA film of about 5 nm was deposited on the stamps, which increased the hydrophilicity, and which remained stable for at least several months. These surface-modified stamps were used to transfer polar inks by microCP. The employed microCP schemes are as follows: (a) a second generation of dendritic ink having eight dialkyl sulfide end groups to fabricate patterns on gold substrates by positive microCP, (b) fluorescent guest molecules on beta-cyclodextrin (beta-CD) printboards on glass employing host-guest recognition, and (c) Lucifer Yellow ethylenediamine resulting in covalent patterning on an aldehyde-terminated glass surface. All experiments resulted in an excellent performance of all three PPAA-coated stamp materials to transfer the polar inks from the stamp surface to gold and glass substrates by microCP, even from aqueous solutions.