Biomedical and ecosafety assessment of marine fish collagen capped silver nanoparticles.

In the rapidly evolving landscape of silver nanoparticles (Ag NPs) synthesis, the focus has predominantly been on plant-derived sources, leaving the realm of biological or animal origins relatively uncharted. Breaking new ground, our study introduces a pioneering approach: the creation of Ag NPs using marine fish collagen, termed ClAg NPs, and offers a comprehensive exploration of their diverse attributes. To begin, we meticulously characterized ClAg NPs, revealing their spherical morphology, strong crystalline structure, and average diameter of 5 to 100 nm. These NPs showed potent antibacterial activity, notably against S. aureus (gram-positive), surpassing their efficacy against S. typhi (gram-negative). Additionally, ClAg NPs effectively hindered the growth of MRSA biofilms at 500 µg/mL. Impressively, they demonstrated substantial antioxidant capabilities, out performing standard gallic acid. Although higher concentrations of ClAg NPs induced hemolysis (41.804 %), lower concentrations remained non hemolytic. Further evaluations delved into the safety and potential applications of ClAg NPs. In vitro cytotoxicity studies on HEK 293 and HeLa cells revealed dose-dependent toxicity, with IC50 of 75.28 µg/mL and 79.13 µg/mL, respectively. Furthermore, ClAg NPs affected seed germination, root, and shoot lengths in Mung plants, underscoring their relevance in agriculture. Lastly, zebrafish embryo toxicity assays revealed notable effects, particularly at 500 µg/mL, on embryo morphology and survival rates at 96 hpf. In conclusion, our study pioneers the synthesis and multifaceted evaluation of ClAg NPs, offering promise for their use as versatile nano therapeutics in the medical field and as high-value collagen-based nanobiomaterial with minimal environmental impact.

Structural basis for the inhibition of SARS-CoV2 main protease by Indian medicinal plant-derived antiviral compounds.

A novel coronavirus (SARS-CoV2) has caused a major outbreak in humans around the globe, and it became a severe threat to human healthcare than all other infectious diseases. Researchers were urged to discover and test various approaches to control and prevent such a deadly disease. Considering the emergency and necessity, we screened reported antiviral compounds present in the traditional Indian medicinal plants for the inhibition of SARS-CoV2 main protease. In this study, we used molecular docking to screen 41 reported antiviral compounds that exist in Indian medicinal plants and shown amentoflavone from the plant Torreyanucifera with a higher docking score. Furthermore, we performed a 40 ns atomic molecular dynamics simulation and free binding energy calculations to explore the stability of the top five protein-ligand complexes. Through the article, we insist that the amentoflavone, hypericin and Torvoside H from the traditional Indian medicinal plants may be used as a potential inhibitor of SARS-CoV2 main protease and further biochemical experiments could shed light on understanding the mechanism of inhibition by these plant-derived antiviral compounds.Communicated by Ramaswamy H. Sarma.

Biomacromolecules of chitosan - Bacopa saponin based LipL32 gene delivery system for leptospirosis therapy.

Leptospirosis is a severe bacterial infectious disease caused by the organisms belonging to the genus of Leptospira. The chitosan/Bacopa saponin/tripolyphosphate (CS/BS/TPP) nanoparticles conjugated with recombinant DNA vaccines were designed against Leptospirosis. Chitosan, a polysaccharide is suitable for delivery of drug, and gene due to its bio-compatible and biodegradable properties. Bacopa saponins are used for the induction of the immune response against microbial infections. The recombinant DNA vaccine construct was composed of the leptospiral outer membrane LipL32 gene tagged with EGFP and hGMCSF adjuvant in the pVAX1 mammalian expression vector along with the Cytomegalovirus (CMV) promoter. These recombinant DNA vaccine constructs was termed as pVAX1-EGFP-LipL32 and pVAX1-EGFP-hGMCSF-LipL32, and these constructs were conjugated with CS/BS/TPP nanoparticles by using the ionic gelation technique. Thus, CS/BS/TPP conjugated nanoparticle DNA vaccine was confirmed by functionality (FT-IR), crystalline nature (XRD) and surface charge (Zeta potential). The 90% encapsulation efficiency was observed in the conjugated nanoparticle DNA vaccine. In contrast, cell viability analysis validated that the synthesized DNA conjugated CS/BS/TPP nanoparticles showed low cytotoxicity up to 10 mg/mL. The results showed here are the initial establishment of DNA vaccine conjugated nanoparticles, which can be used as a potential anti-leptospiral vaccine.

Natural deep eutectic solvent supported targeted solid-liquid polymer carrier for breast cancer therapy.

Solid-liquid nanocarriers (SLNs) are at the front of the rapidly emerging field of medicinal applications with a potential role in the delivery of bioactive agents. Here, we report a new SLN of natural deep eutectic solvent (NADES) and biotin-conjugated lysine-polyethylene glycol copolymer. The SLN system was analyzed for its functional groups, thermal stability, crystalline nature, particle size, and surface morphology through the instrumental analysis of FT-IR, TGA, XRD, DLS, SEM, and TEM. Encapsulation of PTX (paclitaxel) and 7-HC (7-hydroxycoumarin) with the SLN was carried out by dialysis, and UV-visible spectra evidenced the drug loading capacity and higher encapsulation efficiency obtained. The enhanced anticancer potential of PTX- and 7-HC-loaded SLN was assessed in vitro, and the system reduces the cell viability of MDA-MB-231 cells. The PTX- and 7-HC-loaded SLN system was investigated in a breast cancer-induced rat model via in vivo studies. It shows decreased lysosomal enzymes and increased levels of caspase to cure breast tumors. It very well may be reasoned that the designed PTX- and 7-HC-loaded SLN system has strong anticancer properties and exhibits potential for delivery of drug molecules in cancer treatment.

Fabrication of bioactive rifampicin loaded κ-Car-MA-INH/Nano hydroxyapatite composite for tuberculosis osteomyelitis infected tissue regeneration.

Biocompatible polymers and ceramic materials have been identified as vital components to fabricate drug delivery and tissue engineering applications because of their high drug loading capability, sustained release and higher mechanical strength with remarkable in-vivo bioavailability. In the present work, initially we designed κ-carrageenan grafted with maleic anhydride and then reacted it with isoniazid drug (κ-Car-MA-INH). The polymeric system was cross linked with nanohydroxyapatite (NHAP) via electrostatic interaction followed by the addition of rifampicin (RF) and loaded to fabricate κ -Car-MA-INH/NHAP/RF nanocomposites. The chemical modification and interaction of drug with the polymeric-ceramic system were characterised by Fourier Transform Infrared spectroscopy (FT-IR). The zeta potential of the κ -Car-MA-INH/NHAP/RF nanocomposite was observed to be -20.04 mV using Zetasizer. The in vitro drug release studies demonstrated that the nanocomposite releases 76% of RF and 82% of INH in 12 days at pH 5.5. Scanning Electron Microscope analysis revealed the structural deformation of Staphylococcus aureus and Klebsiella pneumoniae upon treatment with this nanocomposite. By using ex-vivo studies combined with physio-chemical characterization methods on the erythrocytes, L929 and MG-63 cell lines, this composite was found to be biocompatible, non-cytotoxic and inducing cell proliferation with less significant hemolysis. Thus, our modified drug delivery nanocomposites afforded higher drug bioavailability with large potential for fabrication as long-acting drug delivery nanocomposites, especially with hydrophobic drugs inducing the growth of osteoblastic bone cells.

Versatile pH-Responsive Chitosan-g-Polycaprolactone/Maleic Anhydride-Isoniazid Polymeric Micelle To Improve the Bioavailability of Tuberculosis Multidrugs.

The potential of polymeric micelles constructed by coalescing natural and synthetic polymers for tuberculosis (TB) treatment was evaluated in this work. We designed a polymeric micelle to improve the delivery of anti-TB drugs (rifampicin [RF] and isoniazid [INH]). The polymeric core was synthesized in the following order: initially chitosan (CS) was grafted with polycaprolactone (PCL) to form CS-g-PCL followed by amide bond formation with maleic anhydride-isoniazid (MA-INH); finally, CS-g-PCL was conjugated with the MA-INH moiety to form the CS-g-PCL/MA-INH polymeric core. Another anti-TB drug, RF, was loaded onto CS-g-PCL/MA-INH through dialysis. The changes in the nature of functional groups and crystallinity were investigated by Fourier transform infrared spectroscopy and X-ray diffraction analysis, respectively. The shape and size of CS-g-PCL/MA-INH and RF-CS-g-PCL/MA-INH were analyzed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. The cumulative drug release profiles were measured by UV-visible spectrophotometry and HPLC analysis. The antimicrobial activity of the loaded micelles was evaluated by finding the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and bacterial cell rupture analyses. The nontoxic nature of the micelles was assessed by ex vivo studies on U937 and L929 cell lines and erythrocytes by performing an MTT assay, apoptosis assay, and hemolysis assay. Ex vivo cellular uptake and in vivo internalization of the INH- and RF-containing micelles were tested on U937 cells and zebrafish using fluorescence microscopy analysis. All of the observations indicate that the multi-TB drug-loaded polymeric micelle is a safe and effective system for the delivery of anti-TB drugs without affecting the mycobactericidal activity.

Protective effect of antigen excess immune complex in guinea pigs infected with Mycobacterium tuberculosis.

Background & objectives: : Immune complexes (ICs) play a crucial role which can either be beneficial or pathological to the host. Involvement of circulating immune complexes (CICs) has been shown in tuberculosis (TB) cases (adults and neonates form), but its immunomodulatory effect has not been studied in vivo. Hence, this study was carried out to understand and explore the prognostic therapeutic potential of CICs on the host immune system in guinea pigs animal TB model. Methods: In this study, the guinea pigs (group I) were immunized with in vitro synthesized antigen excess IC (AgX-IC), group II with antibody excess IC (AbX-IC) and group III with phosphate-buffered saline. All these animals were sensitized with Mycobacterium tuberculosis H37Rv before immunization and subsequently infected with M. tuberculosis H37Rv strain post-immunization with IC. Results: Mortality was observed in animals belonging of groups II and III, while all animals in group I survived. A steady increase in the body weight of animals immunized with AgX-IC was observed when compared to the other groups. The infection load in the spleen and lungs was less in animals from group I when compared to the other groups. The CICs were found to be in higher concentration in serum of IC-immunized guinea pigs when compared to ICs non-immunized animals. Interpretation & conclusions: Based on our findings, it can be speculated that the ICs may have a protective immunomodulatory role pertaining to disease progression and development of pathology. As a new perspective, with further insight into the underlying mechanism of action and correlation with clinical data, ICs may also be used as a potential tool for assessing the immune status of the infected individuals, especially the close contacts of TB patients.