Nanoparticle-reinforced polymer-based scaffolding matrices as artificial bone-implant materials are potential suitors for bone regenerative medicine as they simulate the native bone. In the present work, a series of bioinspired, osteoconductive tricomposite scaffolds made up of nanohydroxyapatite (NHA) embedded xanthan gum−chitosan (XAN−CHI) polyelectrolyte complex (PEC) are explored for their bone-regeneration potential. The Fourier transform infrared spectroscopy studies confirmed complex formation between XAN and CHI and showed strong interactions between the NHA and PEC matrix. The X-ray diffraction studies indicated regulation of the nanocomposite (NC) scaffold crystallinity by the physical cues of the PEC matrix. Further results exhibited that the XAN−CHI/NHA5 scaffold, with a 50/50 (polymer/NHA) ratio, has optimized porous structure, appropriate compressive properties, and sufficient swelling ability with slower degradation rates, which are far better than those of CHI/NHA and other XAN−CHI/NHA NC scaffolds. The simulated body fluid studies showed XAN− CHI/NHA5 generated apatite-like surface structures of a Ca/P ratio ∼1.66. Also, the in vitro cell−material interaction studies with MG-63 cells revealed that relative to the CHI/NHA NC scaffold, the cellular viability, attachment, and proliferation were better on XAN−CHI/NHA scaffold surfaces, with XAN−CHI/ NHA5 specimens exhibiting an effective increment in cell spreading capacity compared to XAN−CHI/NHA4 and XAN−CHI/ NHA6 specimens. The presence of an osteo-friendly environment is also indicated by enhanced alkaline phosphatase expression and protein adsorption ability. The higher expression of extracellular matrix proteins, such as osteocalcin and osteopontin, finally validated the induction of differentiation of MG-63 cells by tricomposite scaffolds. In summary, this study demonstrates that the formation of PEC between XAN and CHI and incorporation of NHA in XAN−CHI PEC developed tricomposite scaffolds with robust potential for use in bone regeneration applications.

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The present frontiers of bone tissue engineering are being pushed by novel biomaterials that exhibit phenomenal biocompatibility and adequate mechanical strength. In this work, we fabricated a ternary system incorporating nano-hydroxyapatite (n-HA)/gum arabic (GA)/κ-carrageenan (κ-CG) with varying concentrations, i.e., 60/30/10 (CHG1), 60/20/20 (CHG2), and 60/10/30 (CHG3). A binary system with n-HA and GA was also prepared with a ratio of 60/40 (HG) and compared with the ternary system. A rapid mineralization of the apatite layer was observed for the ternary systems after incubation in simulated body fluid (SBF) for 15 days as corroborated by scanning electron microscopy (SEM). CHG2 exhibited the maximum apatite layer deposition. Further, the nanocomposites were physicochemically analyzed by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and mechanical testing. Their results revealed a substantial interaction among the components, appropriate crystallinity, and significantly enhanced compressive strength and modulus for the ternary nanocomposites. The greatest mechanical strength was achieved by the scaffold containing equal amounts of GA and κ-CG. The cytotoxicity was evaluated by culturing osteoblast-like MG63 cells, which exhibited the highest cell viability for the CHG2 nanocomposite system. It was further supported by confocal microscopy, which revealed the maximum cell proliferation for the CHG2 scaffold. In addition, enhanced antibacterial activity, protein adsorption, biodegradability, and osteogenic differentiation were observed for the ternary nanocomposites. Osteogenic gene markers, such as osteocalcin (OCN), osteonectin (ON), and osteopontin (OPN), were present in higher quantities in the CHG2 and CHG3 nanocomposites as confirmed by western blotting. These results substantiated the pertinence of n-HA-, GA-, and κ-CG-incorporated ternary systems to bone implant materials.

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Nano-sized drug delivery systems (NDDS) have been widely exploited to achieve targeted delivery of pharmaco-materials. Traditional pharmaceutical approaches, implied in the synthesis of nano-formulations, are obscure owing to the incompatible physico-chemical properties of the core drug as well as some other factors crucial in development of NDDS. Infact, most of the existing methods used in development of NDDS rely on usage of additives or excipients, a special class of chemicals. Barring few exceptions, the usage of synthetic excipients ought to be curtailed because of several associated undesirable features. Such issues necessitate strategies that lead to development of the synthetic excipient free drug delivery system. Plant based extracts have great potential to induce synthesis of nano-sized particles. Considering this fact, here we propose a prototype employing orange fruit juice (OJ) to facilitate bio-mediated synthesis of nano-sized supra-molecular assemblies of 5-fluorouracil (5-FU), a potent anticancer drug. The as-synthesized 5-FU Nanoparticles (NPs) retained the anti-neoplastic efficacy of the parent compound and induced apoptosis in cancer cells. The novel 5-FU NPs formulation demonstrated enhanced efficacy against DMBA induced experimental fibrosarcoma in the mouse model when compared to the micro-sized crystals of parent 5-FU drug.

Among various metal-based nanoparticles, silver nanoparticles (AgNPs) manifest superior inhibitory effects against several microorganisms. In fact, the AgNP-based treatment has been reported to inhibit both sensitive and resistant isolates of bacteria and other disease-causing microbes with equal propensity. Keeping this fact into consideration, we executed bio-mediated synthesis of AgNPs employing extract of flower and various other parts (such as bud and leaf) of the Hibiscus rosa-sinensis plant. The physicochemical characterization of as-synthesized AgNPs was executed employing transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, Fourier transform infrared (FTIR) spectroscopy, and UV-Vis spectroscopy, etc. The as-synthesized AgNPs demonstrated strong antimicrobial activity against both Gram-positive and Gram-negative bacteria with equal propensity. The as-synthesized AgNPs successfully inhibited Streptococcus mutans (S. mutans), one of the main causative bacteria responsible for dental caries. Considering the fact that orthodontic appliances facilitate infliction of the oral cavity with a range of microbes including S. mutans, we determined the growth inhibitory and anti-adherence activities of AgNPs on orthodontic appliances. We performed microbiological assays employing AgNPs adsorbed onto the surface of nickel–titanium (Ni-Ti) orthodontic wires. A topographic analysis of the decontaminated Ni-Ti orthodontic wires was performed by scanning electron microscopy. In addition to antimicrobial and anti-biofilm activities against oral S. mutans, the as-fabricated AgNPs demonstrated significant inhibitory and anti-biofilm properties against other biofilm-forming bacteria such as Escherichia coli and Listeria monocytogenes.

In the present study, we investigated potential of chitosan-based nanoparticles (CNPs) to deliver loaded therapeutic molecules to pathogen harboring macrophages. We fabricated stable CNPs employing ionic cross-linking method and evaluated their potential to target RAW 264.7 cells. The physicochemical characterization of as-synthesized CNPs was determined using electron microscopy, infrared microscopy and zeta potential measurement. Next, cellular uptake and intracellular localization studies of CNPs were followed in living RAW264.7 cells using confocal microscopy. We found that both Acr-1 loaded (CNP-A) and 4-SO4-GalNAc ligand harboring (CNP-L) chitosan nanoparticle experience increased cellular uptake by Mycobacterium smegmatis infected RAW cells. Following cellular digestion in model macrophage cell line (RAW), CNPs provide an increased immune response. Further, 4-SO4-GalNAc bearing CNP-L exhibits high binding affinity as well as antibacterial efficacy toward M. smegmatis. The data of the present study suggest that CNP-based nanoparticle offer a promising delivery strategy to target infected macrophages for prevention and eradication of intracellular pathogens such as M. smegmatis.

Tuberculosis (TB) is a significant and continuing problem worldwide, with a death toll of around 1.5 million human lives annually. BCG, the only vaccine against TB, offers a varied degree of protection among human subjects in different regions and races of the world. The majority of the population living near the tropics carries a varying degree of tolerance against BCG due to the widespread prevalence of non-tuberculous mycobacteria (NTM). Interestingly, ≈90% of the Mycobacterium tuberculosis (Mtb) infected population restrain the bacilli on its own, which strengthens the notion of empowering the host immune system to advance the protective efficacy of existing mycobacterial vaccines. In general, Mtb modulates IL-10/STAT3 signaling to skew host mononuclear phagocytes toward an alternatively activated, anti-inflammatory state that helps it thrive against hostile immune advances. We hypothesized that modulating the IL-10/STAT3 driven anti-inflammatory effects in mononuclear cells may improve the prophylactic ability of TB vaccines. This study investigated the immunotherapeutic ability of a porphyrin based small molecule inhibitor of IL-10/STAT3 axis, 5, 15-diphenyl porphyrin (DPP), in improving anti-TB immunity offered by second generation recombinant BCG30 (rBCG30-ARMF-II®) vaccine in mice. The DPP therapy potentiated vaccine induced anti-TB immunity by down-modulating anti-inflammatory responses, while simultaneously up-regulating pro-inflammatory immune effector responses in the immunized host. The employed DPP based immunotherapy led to the predominant activation/proliferation of pro-inflammatory monocytes/macrophages/DCs, the concerted expansion of CD4+/CD8+ effector and central memory T cells, alongside balanced Th17 and Treg cell amplification, and conferred augmented resistance to aerosol Mtb challenge in rBCG30 immunized BALB/c mice.