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Surface-modified dl-lactide/glycolide copolymer (PLGA) microspheres with chitosan (CS) were developed for nasal immunization using recombinant Hepatitis B (HBsAg) surface protein for the induction of humoral, cellular and mucosal immunity. Modified PLGA microspheres were characterized in vitro for their size, shape, entrapment efficiency and zeta potential. The nasal clearance rate was evaluated by gamma scintigraphy in rabbits. The antigen integrity, in vitro release and its stability at 37 °C were also evaluated. The designed cationic microspheres possessed 27.2 mV zeta potential and an average size less than 10 μm with antigen loading efficiency of 80 ± 5%. However, zeta potential of unmodified PLGA microspheres was measured to be negative (−8.7 mV). The modified PLGA microspheres showed the lowest nasal clearance rate when compared with unmodified PLGA microspheres and lactose powder. The antigen integrity was retained intact in encapsulated form as well as on release. The immune-stimulating activity was studied by measuring anti-HBsAg titre, secretory IgA level in serum, vaginal, nasal and salivary secretions (mucosal secretions) and cytokine level (interleukin-2 (IL-2) and interferon-γ (IFN-γ)) in spleen homogenates following nasal administration of modified PLGA microspheres in Balb/c mice and compared with alum-HBsAg vaccine injected subcutaneously. The serum anti-HBsAg titre obtained after nasal administration of modified PLGA microspheres was comparable with titre recorded after alum-HBsAg was administered subcutaneously. Moreover, alum-HBsAg vaccine did not elicit sIgA in mucosal secretions as it was induced and measured in the case of nasal administration of modified PLGA microspheres. Similarly, there was no cellular response (cytokine level) in case of alum-HBsAg vaccine. Modified PLGA microspheres (cationic microspheres) thus produced humoral (both systemic and mucosal) and cellular immune responses upon nasal administration. These data demonstrate high potential of modified PLGA microspheres for their use as a carrier adjuvant for nasal subunit vaccines.

Combination vaccines are effective in simplifying complex vaccination schedules involving multiple vaccines. A fully liquid hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)- hepatitis B (HepB)-inactivated poliovirus (IPV)-Haemophilus influenzae b (Hib) vaccine (HEXASIIL®), manufactured by Serum Institute of India Pvt. Ltd. was tested for safety and immunogenicity following booster vaccination. This was a phase-II/III, open label, multicentric, controlled trial in toddlers (phase II) and infants (phase III) in India. This manuscript presents results of phase II. Healthy toddlers aged 12–24 months were randomized (1:1) to receive a 0.5 ml booster dose of HEXASIIL® or comparator Pentavac SD + Poliovac, intramuscularly and followed for 28 days for safety assessment. Blood samples were collected pre-vaccination and 28 days post-vaccination to assess immunogenicity. Descriptive summary statistics were provided for safety and immunogenecity analyses. A total of 223 subjects were randomized. One subject droped out prior to dosing, due to consent withdrawal. Thus, 222 subjects received study vaccine (110 HEXASIIL® and 112 comparator). Frequency of solicited adverse events was comparable between HEXASIIL® and comparator (85.5 % vs 90.2 %). Most local and systemic solicited AEs were mild to moderate in severity. All events resolved completely without any sequelae and none led to subject discontinuation. No vaccine related serious AE was reported. Post vaccination, seroprotection rates against tetanus, Hib and polio type 1 and 3 were 100 % in both the groups. Seroprotection rates for diphtheria (99.1 % vs 100 %) and polio type 2 (98.2 % vs 100 %) were observed in HEXASIIL® and comparator group, respectively. For Hepatitis B, seroprotection was >99 % in both groups. Seroconversion observed for Bordetella Pertussis (94.5 % vs 95.4 %) and Pertussis Toxin (77.1 % vs 87.2 %) in HEXASIIL® and comparator group, respectively. HEXASIIL® vaccine was found to be safe and immunogenic in toddlers and supported its further clinical development in infants. Clinical Trial Registration – CTRI/2019/11/022052. •Combination vaccines simplify vaccination schedules and improve compliance.•HEXASIIL® vaccine was compared to licensed DTwP-HepB-Hib + IPV vaccines.•HEXASIIL® had good safety and immunogenicity profile.•The data supported further evaluation of HEXASIIL® in infants.

Tri-methyl chitosan synthesis accompanies polymer chain scission, which may affect the carrier and adjuvant properties of the polymer. The main objective of this study was to synthesize the tri-methylated chitosan using mild (TMC-M) and conventional (TMC) method and compare their efficacy as nasal vaccine delivery vehicle. During in vitro studies TMC-M nanoparticles showed the lowest nasal clearance rate when compared with chitosan (CS) and TMC nanoparticles. The immunogenicity of nanoparticles based delivery system(s) was assessed by measuring anti-HBsAg antibody titer in mice serum and secretions after intranasal administration. The alum based HBsAg vaccine injected subcutaneously was used as positive control. Results indicated that alum based HBsAg induced strong humoral but negligible mucosal immunity. However, TMC-M nanoparticles induced stronger immune response at both of the fronts as compared to generated by CS or TMC nanoparticles. Present study demonstrates that TMC-M can be a better carrier adjuvant for nasal subunit vaccines.

A fully liquid hexavalent containing Diphtheria (D), Tetanus (T) toxoids, whole cell Pertussis (wP), Hepatitis B (Hep B), type 1, 2, 3 of inactivated poliovirus (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (DTwP-HepB-IPV-Hib vaccine, HEXASIIL ® ) was tested for lot-to-lot consistency and non-inferiority against licensed DTwP-HepB-Hib + IPV in an open label, randomized Phase II/III study. In Phase III part, healthy infants received DTwP-HepB-IPV-Hib or DTwP-HepB-Hib + IPV vaccines at 6, 10 and 14 weeks of age. Blood samples were collected prior to the first dose and 28 days, post dose 3. Non inferiority versus DTwP-HepB-Hib + IPV was demonstrated with 95% CIs for the treatment difference for seroprotection/seroconversion rates. For DTwP-HepB-IPV-Hib lots, limits of 95% CI for post-vaccination geometric mean concentration ratios were within equivalence limits (0.5 and 2). Vaccine was well-tolerated and no safety concerns observed. Clinical Trial Registration – CTRI/2019/11/022052

Interleukin-6 (IL-6) signaling network has been implicated in oncogenic transformations making it attractive target for the discovery of novel cancer therapeutics. In this study, potent antiproliferative and apoptotic effect of diacerein were observed against breast cancer. In vitro apoptosis was induced by this drug in breast cancer cells as verified by increased sub-G 1 population, LIVE/DEAD assay, cell cytotoxicity and presence of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, as well as downregulation of antiapoptotic proteins Bcl-2 and Bcl-xL and upregulation of apoptotic protein Bax. In addition, apoptosis induction was found to be caspase dependent. Further molecular investigations indicated that diacerein instigated apoptosis was associated with inhibition of IL-6/IL-6R autocrine signaling axis. Suppression of STAT3, MAPK and Akt pathways were also observed as a consequence of diacerein-mediated upstream inhibition of IL-6/IL-6R. Fluorescence study and western blot analysis revealed cytosolic accumulation of STAT3 in diacerein-treated cells. The docking study showed diacerein/IL-6R interaction that was further validated by competitive binding assay and isothermal titration calorimetry. Most interestingly, it was found that diacerein considerably suppressed tumor growth in MDA-MB-231 xenograft model. The in vivo antitumor effect was correlated with decreased proliferation (Ki-67), increased apoptosis (TUNEL) and inhibition of IL-6/IL-6R-mediated STAT3, MAPK and Akt pathway in tumor remnants. Taken together, diacerein offered a novel blueprint for cancer therapy by hampering IL-6/IL-6R/STAT3/MAPK/Akt network.

Antireflection coatings (ARCs) have become one of the key techniques for mass production of Si solar cells. They are generally performed by vacuum processes such as thermal evaporation, sol–gel and plasma-enhanced chemical vapor deposition. In this work, RF sputtering method was adopted to prepare the ARCs for the non-textured polycrystalline Si solar cells. The RF sputter coated strontium titanate(SrTiO 3 ), barium titatnate(BaTiO 3 )and SrTiO 3 -BaTiO 3 (mechanical blends). Si solar cells were inspected through various characterisation techniques. Through RF sputter deposition technique, thin films with good uniformity can be achieved easily. The influence of ARC on solar cell samples were studied through evaluation of structural, optical and electrical properties of coated and uncoated samples. The structural characterization was carried out by X-ray diffraction (XRD) and scanning electron microscopy (SEM).The electrical resistivity was measured in dark at room temperature using four-point probe technique. UV–visible spectroscopy was utilised for determining optical characterization. It was found that SrTiO 3 -BaTiO 3 blend coated cell (M3)has considerable effect on the performance of solar cell as compare to uncoated and other coated solar cells. The maximum power conversion efficiencies (PCE) of 19.58% and 21.15% were achieved for M3 solar cell in presence of solar and neodymium irradiation under open and controlled atmospheric conditions. Neodymium light radiation was similar to the natural sun light and can be used for growing plants and veterinaries under enclosed surface. Based on the results, SrTiO 3 -BaTiO 3 blends found to be an appropriate ARC material for minimising scattering of incident photons.

One of the major environmental issues of textile industries is the discharge of large quantities of textile effluents, which are source of contamination of water bodies on surface of earth and quality of groundwater. The effluents are toxic, non-biodegradable, carcinogenic and prodigious threats to human and aquatic creatures. Since textile effluents can be treated efficiently and effectively by various advanced oxidation processes (AOPs). Among the various AOPs, cold atmospheric pressure plasma is a promising method among many prominent techniques available to treat the effluents. In this paper, we report about the degradation of simulated effluent, namely Direct Orange-S (DO-S) aqueous solution, using nonthermal atmospheric pressure plasma jet. The plasma treatment of DO-S aqueous solution was carried out as a function of various operating parameters such as potential and treatment time. The change in properties of treated DO-S dye was investigated by means of various analytical techniques such as high-performance liquid chromatography, UV–visible (UV-Vis) spectroscopy and determination of total organic content (TOC). The reactive species present in the samples were identified using optical emission spectrometry (OES). OES results confirmed that the formation of reactive oxygen and nitrogen species during the plasma treatment in the liquid surface was responsible for dye oxidation and degradation. Degradation efficiency, as monitored by color removal efficiency, of 96% could be achieved after 1 h of treatment. Concurrently, the TOC values were found to decrease with plasma treatment, implying that the plasma treatment process enhanced the non-toxicity nature of DO-S aqueous solution. Toxicity of the untreated and plasma-treated dye solution samples was studied using Escherichia coli (E. coli) and Staphylococcus (S. aureus) organisms, which demonstrated that the plasma-treated dye solution was non-toxic in nature compared with untreated one.

Wound patches are essential for wound healing, yet developing patches with enhanced mechanical and biological properties remains challenging. This study aimed to enhance the mechanical and biological properties of polyurethane (PU) by incorporating magnesium chloride (MgCl ) into the patch. The composite patch was fabricated using the electrospinning technique, producing nanofibers from a mixture of PU and MgCl solutions. The electrospun PU/MgCl was then evaluated for various physico-chemical characteristics and biological properties to determine its suitability for wound healing applications. Tensile strength testing showed that the mechanical properties of the composite patch (10.98 ± 0.18) were significantly improved compared to pristine PU (6.66 ± 0.44). Field scanning electron microscopy (FESEM) revealed that the electrospun nanofiber patch had a smooth, randomly oriented non-woven structure (PU - 830 ± 145 nm and PU/MgCl - 508 ± 151 nm). Fourier infrared spectroscopy (FTIR) confirmed magnesium chloride's presence in the polyurethane matrix via strong hydrogen bond formation. Blood compatibility studies using coagulation assays, including activated partial thromboplastin time (APTT), prothrombin time (PT), and hemolysis assays, demonstrated improved blood compatibility of the composite patch (APTT - 174 ± 0.5 s, PT - 91 ± 0.8s, and Hemolytic percentage - 1.78%) compared to pristine PU (APTT - 152 ± 1.2s, PT - 73 ± 1.7s, and Hemolytic percentage - 2.55%). Antimicrobial testing showed an enhanced zone of inhibition (Staphylococcus aureus - 21.5 ± 0.5 mm and Escherichia coli - 27.5 ± 2.5 mm) compared to the control, while cell viability assays confirmed the non-cytotoxic nature of the developed patches on fibroblast cells. The study concludes that adding MgCl to PU significantly improves the mechanical, biological, and biocompatibility properties of the patch. This composite patch shows potential for future wound healing applications, with further studies needed to validate its efficacy in-vivo.

Qi J, Zhang H, Wang Y, Mani MP, Jaganathan SK. Int J Nanomedicine. 2018;13:2777-2788.Affiliation 5 for Saravana Kumar Jaganathan was incorrectly presented. The correct affiliation 5 should have been:5Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, VietnamRead the original article

The main objective of this study was to prepare Hepatitis B surface antigen (HBsAg) loaded poly(lactic-co-glycolic acid) (PLGA), Trimethyl chitosan (TMC) as well as TMC-coated PLGA nanoparticles and compare their efficacy as nasal vaccine. The developed formulations were characterized for size, zeta potential, entrapment efficiency, mucin adsorption ability, Dentritic cells interaction, in vitro and in vivo studies. PLGA nanoparticles demonstrated negative zeta potential whereas TMC and PLGA–TMC nanoparticles showed higher positive zeta potential. Results indicated that TMC and PLGA–TMC nanoparticles demonstrated substantially higher mucin adsorption when compared to PLGA nanoparticles. The nanoparticles were nontoxic to isolated nasal epithelium. Immunogenicity increased as a function of particle size upon nasal administration. HBsAg encapsulated in PLGA–TMC particles elicited a significantly higher secretory (IgA) immune response compared to that encapsulated in PLGA and TMC particles. Similar to in vivo immune response data, fluorescent-labelled nanoparticles of smaller size are taken up more efficiently by rat alveolar macrophages compared to those of larger size. Results indicated that alum based HBsAg induced strong humoral but less mucosal immunity. However, PLGA–TMC nanoparticles induced stronger immune response at both of the fronts as compared to generated by PLGA or TMC nanoparticles. Present study demonstrates that PLGA–TMC nanoparticles with specific size range can be a better carrier adjuvant for nasal subunit vaccines.