Nanoformulations for dismantling fungal biofilms: The latest arsenals of antifungal therapy.

Globally, fungal infections have evolved as a strenuous challenge for clinicians, particularly in patients with compromised immunity in intensive care units. Fungal co-infection in Covid-19 patients has made the situation more formidable for healthcare practitioners. Surface adhered fungal population known as biofilm often develop at the diseased site to elicit antifungal tolerance and recalcitrant traits. Thus, an innovative strategy is required to impede/eradicate developed biofilm and avoid the formation of new colonies. The development of nanocomposite-based antibiofilm solutions is the most appropriate way to withstand and dismantle biofilm structures. Nanocomposites can be utilized as a drug delivery medium and for fabrication of anti-biofilm surfaces capable to resist fungal colonization. In this context, the present review comprehensively described different forms of nanocomposites and mode of their action against fungal biofilms. Amongst various nanocomposites, efficacy of metal/organic nanoparticles and nanofibers are particularly emphasized to highlight their role in the pursuit of antibiofilm strategies. Further, the inevitable concern of nanotoxicology has also been introduced and discussed with the exigent need of addressing it while developing nano-based therapies. Further, a list of FDA-approved nano-based antifungal formulations for therapeutic usage available to date has been described. Collectively, the review highlights the potential, scope, and future of nanocomposite-based antibiofilm therapeutics to address the fungal biofilm management issue.

A review on multifaceted biomedical applications of heparin nanocomposites: Progress and prospects.

Advances in polymer-based nanocomposites have revolutionized biomedical applications over the last two decades. Heparin (HP), being a highly bioactive polymer of biological origin, provides strong biotic competence to the nanocomposites, broadening the horizon of their applicability. The efficiency, biocompatibility, and biodegradability properties of nanomaterials significantly improve upon the incorporation of heparin. Further, inclusion of structural/chemical derivatives, fractionates, and mimetics of heparin enable fabrication of versatile nanocomposites. Modern nanotechnological interventions have exploited the inherent biofunctionalities of heparin by formulating various nanomaterials, including inorganic/polymeric nanoparticles, nanofibers, quantum dots, micelles, liposomes, and nanogels ensuing novel functionalities targeting diverse clinical applications involving drug delivery, wound healing, tissue engineering, biocompatible coatings, nanosensors and so on. On this note, the present review explicitly summarises the recent HP-oriented nanotechnological developments, with a special emphasis on the reported successful engagement of HP and its derivatives/mimetics in nanocomposites for extensive applications in the laboratory and health-care facility. Further, the advantages and limitations/challenges specifically associated with HP in nanocomposites, undertaken in this current review are quintessential for future innovations/discoveries pertaining to HP-based nanocomposites.

Baicalin functionalized PEI-heparin carbon dots as cancer theranostic agent.

The worldwide prevalence of cancer and its significantly rising risks with age have garnered the attention of nanotechnology for prompt detection and effective therapy with minimal or no adverse effects. In the current study, heparin (HP) polymer derived heteroatom (N, S-) co-doped CDs were synthesized using hydrothermal synthesis method to efficiently deliver natural anticancer compound baicalin (BA). Heparin carbon dots (HCDs) were passivated with polyethylenimine (PEI) to improve its fluorescence quantum yield. The surface passivation of CDs by polycationic PEI polymer not only facilitated loading of BA, but also played a crucial role in the pH-responsive drug delivery. The sustained release of BA (up to 80 %) in mildly acidic pH (5.5 and 6.5) conditions endorsed its drug delivery potential for cancer-specific microenvironments. BA-loaded PHCDs exhibited enhanced anticancer activity as compared to BA/PHCDs indicating the effectiveness of the nanoformulation, Furthermore, the flow cytometry analysis confirmed that BA-PHCDs treated cells were arrested in the G2/M phase of cell cycle and had a higher potential for apoptosis. Bioimaging study demonstrated the excellent cell penetration efficiency of PHCDs with complete cytoplasmic localization. All this evidence comprehensively demonstrates the potency of BA-loaded PHCDs as a nanotheranostic agent for cancer.

Bifunctional Dalteparin/Enoxaparin coated nanosilver formulation to prevent bloodstream infections during hemodialysis.

Catheter-related bloodstream infections (CRBSI) are the major concern of patients undergoing hemodialysis. The current study formulates bifunctional low molecular weight heparin (LMWH) coated nanosilver as an effective anticoagulant and antimicrobial/anti-biofilm agent. Nanosilver formulations were prepared using a microwave-assisted green synthesis approach and stabilized with pharmaceutically approved LMWH such as dalteparin (DL) and enoxaparin (EX) along with unfractionated heparin (HP) as a control. The obtained heparinized (HP/DL/EX) nanosilver was monodisperse, and the size ranged between 15 and 25 nm. DL/EX predominantly stabilized the nanosilver by primarily engaging their negatively charged sulfate groups. The obtained DL/EX coated nanosilver are hemocompatible, showed two times increase in their anticoagulation activity, and are highly potent in inhibiting/eradicating both mono- and polymicrobial biofilms. Henceforth, the observed biocompatible and enhanced bifunctional characteristics of DL/EX coated nanosilver can be used to replace the systemic antibiotics and can be an alternative catheter lock solution to prevent CRBSI in hemodialysis therapy.

Anticoagulation and antibacterial properties of heparinized nanosilver with different morphologies.

Synthesis and characterization of nanoparticles with different morphologies coupled to minimal chemical interventions for sustainable applications is one of the contemporary topics in the field of nanotechnology. In the current study, heparinized silver nanoparticles were synthesized using a chemical reduction method. Different concentrations of heparin were used to investigate its role in the stability and morphological properties of silver nanoparticles. Interestingly, it has been observed that the concentration of the stabilizing agent heparin plays a pivotal role in dictating the size and shape of the nanosilver. As visualized under a transmission electron microscope, nanosilver with different morphological states such as triangles, truncated triangles, hexagon, and spheres has been experimentally trapped. Such modular property of heparin coated nanosilver has also exhibited substantial differences in their anticoagulation and antimicrobial activities.

Dissecting the anti-biofilm potency of kappa-carrageenan capped silver nanoparticles against Candida species.

Global antimicrobial crisis and advent of drug resistant fungal strains has substantially distressed disease management for clinicians. Biodegradable silver nanoparticles (AgNps) emerge as an excellent alternative remedial option. In the current study, the anti-biofilm activity of microwave irradiated kappa-carrageenan (CRG) capped AgNps against Candida albicans, and Candida glabrata was investigated in terms of their effect on reactive oxygen species (ROS) generation, cellular morphology, biochemical composition, and the activity of enzymes of extracellular matrix. Minimum inhibitory concentration and fungicidal concentration value of CRG-AgNps against both Candida spp. ranged between 400 and 500 µg/mL. The 80% of Candida biofilm was inhibited and eradicated by CRG-AgNps at a concentration of ~300 µg/mL. Microscopic studies indicate that CRG-AgNps caused morphological damage through membrane disruption and pore formation. Further, CRG-AgNps generated ROS in a concentration-dependent manner and modulated the composition of Candida biofilm ECM by increasing the carbohydrate and eDNA content. CRG-AgNps also significantly inactivated the hydrolytic enzymes, thus hindering the biofilm forming ability. In conclusion, all these results suggest that the CRG-AgNps are potential antifungal agents against Candida biofilms, and they inhibit/eradicate the fungal biofilms through multiple signalling mechanisms.

Fabrication and Characterization of Bioblocks from Agricultural Waste Using Fungal Mycelium for Renewable and Sustainable Applications.

Recent advances in the field of biomaterials and an ever-growing need to curb the alarming rate of pollution levels have led to the utilization of biodegradable waste to fabricate sustainable materials with tunable properties. The current study investigated the growth kinetics and morphology of Pleurotus ostreatus (P. ostreatus) mycelium grown on different agricultural wastes such as wheat bran, sugarcane, sawdust, and the mixture of these substrates. Further, it delineated the fabrication process of biodegradable "bioblocks" from such agricultural waste using a green synthesis approach and mycelium P. ostreatus as a natural adhesive material. The fabricated bioblocks showed excellent thermal stability, hydrophobic properties, and mechanical strength. The compressive strength of these bioblocks was approximately 6.0-7.5 N/mm2, which is 5-6 times higher than that of the routinely used polystyrene packaging material. These properties of the bioblocks render them fit to replace the non-biodegradable materials that are commonly used in packaging applications, wall paneling, and filtration of toxic wastes.

Physicochemical and Antibacterial Properties of PEGylated Zinc Oxide Nanoparticles Dispersed in Peritoneal Dialysis Fluid.

Owing to the peculiar broad-spectrum antimicrobial activities of zinc oxide nanoparticles (ZnO NPs), we envisaged their use to treat bacterial/mycobacterial/fungal infections during peritoneal dialysis (PD) of end-stage renal failure patients. However, a recent study from our lab showed that ZnO-NPs cannot be employed for the same in their naked form owing to their rapid agglomeration. Also, the naked ZnO-NPs showed strong interaction with organic acids present in the PD fluid (i.e., lactate and citrate present abundantly in almost all biological fluids) resulting in the formation of bioconjugates. Here, we propose that the surface coating of ZnO NPs may inhibit the binding interactions of NPs with the constituents of PD fluid. Therefore, in this study, we have carried out the surface coating of ZnO NPs with polyethylene glycol (PEG) of different molecular weights, followed by the investigations of physicochemical properties of PEGylated ZnO NPs dispersed in PD fluid using nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy. The interaction of PEGylated ZnO NPs has also been studied separately in glucose and lactic acid which are the main constituents of PD fluid and in citric acid. Although the X-ray diffraction and TEM results infer the colloidal stability of PEGylated ZnO NPs in PD fluid, FT-IR, UV-vis, and nuclear magnetic resonance results revealed the binding interactions of PEGylated ZnO NPs with the PD constituents. PEGylated ZnO NPs also interact strongly with the lactic acid and citric acid, leading to agglomeration, as observed previously for uncoated ZnO NPs. Further, the antibacterial activities of bare and PEG-coated ZnO NPs dispersion in PD fluid have been studied. A reduction in the bacterial inhibition effect against Staphylococcus aureus and Escherichia coli was observed for both the bare and PEG-coated ZnO NPs dispersed in PD fluid, indicating that the complex nature of PD fluid counteract on the efficiency of these nanobiotics.

Microwave assisted κ-carrageenan capped silver nanocomposites for eradication of bacterial biofilms.

Maturation of bacterial biofilms and their resistance to recurrent antimicrobial agents results in convoluted infectious diseases. In the current study, kappa-Carrageenan (κ-Carrageenan/CRG), was used to formulate CRG-silver nanocomposites through a facile microwave green synthesis approach. CRG-Ag nanoparticles of size 50 ± 10 nm were obtained by using CRG as a reducing and stabilizing agent. CRG-Ag nanoparticles were highly effective against both S. aureus and P. aeruginosa mediated biofilms and acted as a broad spectrum antibacterial agent even after six months. CRG-Ag nanoparticles encapsulated in KCl cross-linked hydrogel also exhibited excellent thermal stability, and antimicrobial potency. All these results depict that CRG-Ag nanocomposites appear as a promising approach to eradicate bacterial biofilms in food packaging and biomedical applications.

Glycosaminoglycan-based resorbable polymer composites in tissue refurbishment.

Regeneration of tissue structure with the aid of bioactive polymer matrices/composites and scaffolds for respective applications is one of the emerging areas of biomedical engineering. Recent advances in conjugated glycosaminoglycan (GAG) hybrids using natural and synthetic polymers have opened new avenues for producing a wide variety of resorbable polymer matrices. These hybrid scaffolds are low-immunogenic, highly biocompatible and biodegradable with incredible mechanical and tensile properties. GAG-based resorbable polymeric matrices are being exploited in migration of stem cells, cartilage and bone replacement/regeneration and production of scaffolds for various tissue engineering applications. In the current review, we will discuss the role of GAG-based resorbable polymer matrices in the field of regenerative medicine.