FORMULATION OF NANOPARTICLES OF TELMISARTAN INCORPORATED IN CARBOXYMETHYLCHITOSAN FOR THE BETTER DRUG DELIVERY AND ENHANCED BIOAVAILABILITY

  Objective: In this study, we have made an attempt to the developed formulation of nanoparticles (NPs) of telmisartan (TLM) incorporated in carboxymethyl chitosan (CMCS) for the better drug delivery and enhanced bioavailability.Materials and Methods: The NPs size and morphology were investigated by high-resolution transmission electron microscopy and field emission scanning electron microscopy, respectively. The crystal structures and surface functional groups were analyzed using X-ray diffraction pattern, and Fourier transform infrared spectroscopy, respectively.Results: To increase the solubility of TLM by targeted delivery of the drug through polymeric NPs is an alternative efficient, option for increasing the solubility. TLM nanosuspension powders were successfully formulated for dissolution and bioavailability enhancement of the drug. We focused on evaluating the influence of particle size and crystalline state on the in vitro and in vivo performance of TLM.Conclusion: In summary, we have developed a new approach toward the delivery of poorly water-soluble drug TLM by CMCS NPs. The particles having a good drug loading content and drug encapsulation efficiency. The cytotoxicity of the synthesized NPs is also very less

Amelioratory Effect of Nanoconjugated Vancomycin on Spleen during VRSA-Induced Oxidative Stress

Objective. The aim of the present study was to evaluate the possible antioxidant effects of nanoconjugated vancomycin against VRSA infection on select makers of oxidative damage and antioxidant status in spleen. Methods. A coagulase-positive VRSA strain was used for this study. VRSA infection was developed in Swiss mice by intraperitoneal injection of 5 × 106 CFU/mL bacterial solutions. VRSA-infected mice were treated with nanoconjugated vancomycin at its effective dose for 10 days. After decapitation, blood was used for determination of viable bacteria count and spleen was excised from control and experimental groups, homogenized and used for different biochemical estimations. Results. Nitrate level, myeloperoxidase activity, lipid peroxidation, protein oxidation, oxidized glutathione, and DNA fragmentation level were increased significantly (P < 0.05) in spleen of VRSA-infected group as compared to control group, and reduced glutathione level, activity of SOD, CAT, GPx, GR, and GST were decreased significantly (P < 0.05); which were increased or decreased significantly (P < 0.05) near to normal in nanoconjugated vancomycin-treated group. Conclusion. These findings suggest the potential use and beneficial role of nanoconjugated vancomycin against VRSA-infection-induced oxidative stress and DNA damage in spleen

Internalization of Staphylococcus aureus in Lymphocytes Induces Oxidative Stress and DNA Fragmentation: Possible Ameliorative Role of Nanoconjugated Vancomycin

Staphylococcus aureus is the most frequently isolated pathogen causing bloodstream infections, skin and soft tissue infections and pneumonia. Lymphocyte is an important immune cell. The aim of the present paper was to test the ameliorative role of nanoconjugated vancomycin against Vancomycin-sensitive Staphylococcus aureus (VSSA) and vancomycin-resistant Staphylococcus aureus (VRSA) infection-induced oxidative stress in lymphocytes. VSSA and VRSA infections were developed in Swiss mice by intraperitoneal injection of 5 × 106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was adminstrated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was adminstrated to VSSA- and VRSA-infected mice at a similar dose, respectively, for 10 days. Vancomycin and nanoconjugated vancomycin were adminstrated to normal mice at their effective doses for 10 days. The result of this study reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, nitrite generation, nitrite release, and DNA damage and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group, which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These findings suggest the potential use and beneficial role of nanoconjugated vancomycin against VSSA and VRSA infection-induced oxidative stress in lymphocytes

Preparation and characterization of mesoporous cerium oxide for toxic As(V) removal: performance and mechanistic studies

In the present work, the adsorption of carcinogenic pentavalent arsenic (As(V)) from an aqueous solution was studied using mesoporous cerium oxide (MCO). The MCO was synthesized in the precipitation process and confirmed by FT-IR, SEM-EDX, XRD, and BET instrumental techniques. Batch adsorption showed that 95% of As(V) was removed in the optimum conditions of 0.60 g/L adsorbent dose, 10 mg/L initial concentration, time 30 min, and pH 3. Pseudo-secondorder kinetics and the Langmuir isotherm model were fitted to the experimental data. The MCO had a high surface area of 191.97 m2/g and a maximum adsorption capacity of 58.25 mg/g at pH 3. MCO could be able to remove 88% and 82% in the first and second cycles after being desorbed with 0.1 M NaOH solution. The Zeta potential and FTIR studies suggested that electrostatic attraction and ligand exchange mechanisms were responsible for As(V) adsorption

Identification of possible SARS-CoV-2 main protease inhibitors: in silico molecular docking and dynamic simulation studies

Abstract Background COVID-19 was declared a pandemic by the World Health Organisation in 2020 after its outbreak in December 2019 in Wuhan, China. Since researchers have been working to develop specific drugs to cure COVID-19. COVID-19 is caused by the severe acute respiratory cornonavirus2 or popularly known as SARS-CoV2 attacking the ACE2 receptor in the human respiratory system. The main protease translated by the viral genome is a highly conserved protein that plays a crucial role in viral protein replication and transcription. Compounds such as Darunavir and danoprevir have been tested to show potential biological activity against the viral protein, but a high mutation rate defies a permanent solution to this problem. Results In this study, virtual screening of natural ligands (around 170,000 molecules) and FDA-approved repurposed drugs retrieved from ZINC Database was carried out against SARS-CoV2 main protease (PDB ID: 7DJR). Molecular coupling was performed for the top three ligands, where ZINC70699832 showed a significantly good binding affinity of − 11.05 kcal/mol. It has shown an interaction affinity for the residues THR-25, PHE-140, LEU-141, ASN-142, GLY-143, SER-144, CYS-145, MET-165, GLU-166, GLN-189 and GLN-192. The molecular dynamic simulation was also performed using GROMACS, for all complexes where the ZINC70699832–7DJR complex showed stability in terms of root mean square deviation. Conclusion The study recommends that ZINC70699832 has great potential to serve as a potent inhibitor of the main protease of SARS-CoV2 main protease

One pot method to synthesize three-dimensional porous hydroxyapatite nanocomposite for bone tissue engineering

A three-dimensional porous hydroxyapatite nanocomposite has been synthesized by a simple, less energy consuming and cost effective one-pot method. In this study, gelatin foam has been used as pore forming agent and incorporated in carboxymethyl cellulose-hydroxyapatite system in composite formation stage. A three-dimensional porous polymers-hydroxyapatite nanocomposite has been formed as a final product. The synthesized porous nanocomposite has been thoroughly characterized by different techniques. It was found that the nanocomposite is highly porous with almost 80% porosity, and has multi-scale pores from 2.5 to 900 mu m in size. Furthermore, the synthesized porous composite has compressive strength \~ 11.8 +/- 1.5 MPa and modulus \~ 0.243 +/- 0.031 GPa, in the range of cancellous bone. Moreover, the nanocomposite provides favorable environment to cells for proliferation, high alkaline phosphatase (ALP) activity and extracellular mineralization. In vitro degradation of synthesized nanocomposites was tested in simulated body fluid. Results ascertained that the synthesized porous hydroxyapatite nanocomposite would be a promising scaffold for bone tissue engineeri

Facile synthesis of carbon fiber reinforced polymer-hydroxyapatite ternary composite: A mechanically strong bioactive bone graft

Carbon fiber reinforced carboxymethyl cellulose-hydroxyapatite ternary composites have been synthesized by a simple wet precipitation method for weight bearing orthopedic application. Composites were synthesized with the incorporation of chemically functionalized carbon fibers. The functional groups onto the surface of fibers induced the formation of hydroxyapatite at the bridging position through which fibers were effectively bound with matrix. Consequently, the flexural strength and compressive strength of composite have reached to 140 MPa and 118 MPa, respectively. The flexural modulus of the composite is in the range of 9-22 GPa. In-vitro cell study showed that the composite possesses excellent cell proliferation and differentiation ability. With these excellent mechanical and biological properties, synthesized composite exhibits potential to be used as a mechanically compatible bioactive bone graft

Three-dimensional cellulose-hydroxyapatite nanocomposite enriched with dexamethasone loaded metal-organic framework: a local drug delivery system for bone tissue engineering

Three-dimensional cellulose-hydroxyapatite nanocomposite integrated with dexamethasone loaded metal organic framework (HA/DMOF) has been synthesized as a local drug delivery system for bone tissue engineering. Initially, in situ dexamethasone encapsulated metal-organic frameworks (DMOFs) were developed and characterized. The synthesized DMOFs are 60-80nm in size with rhombohedral morphology. Results showed that nearly 16% dexamethasone (Dex) was loaded in DMOFs. These synthesized DMOF nanoparticles were efficiently integrated with carboxymethyl cellulose-hydroxyapatite nanocomposite for the development of three dimensional localized drug delivery system, namely, HA/DMOF. The synthesized HA/DMOF nanocomposite was structurally characterized using various techniques. The mechanical properties of HA/DMOFs were also measured by means of compression test. It was found that the compressive strength and compressive modulus of HA/DMOF nanocomposite are 16.31.57MPa and 0.54 +/- 0.073GPa respectively, which are in the range of cancellous bone. In-vitro release behaviour of Dex from both DMOFs and HA/DMOFs was examined in phosphate buffered solution. It was found that Dex molecules have been released very slowly from HA/DMOF nanocomposite compared to DMOF nanoparticles, and it was sustained for 4weeks. Cytocompatibility of HA/DMOF nanocomposite was evaluated against pre-osteoblast MC3T3 cells. It was found that the synthesized HA/DMOF nanocomposite is compatible to MC3T3 cells. Moreover, the ALP activity and extracellular mineralization capability of cells were enhanced when cultured with HA/DMOF nanocomposite. Results showed that the synthesized HA/DMOF nanocomposite is a promising material for possible therapeutic as well as load-bearing orthopedic applications. GRAPHICS]