Addressing the Global Threat of Multidrug-Resistant Infections: The Role of Ceftazidime-Avibactam Revisited.

Background and objective Bloodstream infections (BSIs) due to multidrug-resistant Gram-negative bacteria (MDR-GNB) pose a significant global health threat amid rising antimicrobial resistance (AMR). This study aimed to investigate the efficacy of ceftazidime-avibactam (CZA) as a therapeutic option for these infections, addressing the urgent need for novel treatments. Materials and methods This study was conducted over one year in the Department of Microbiology, JSS Medical College and Hospital, Mysuru, India, and employed a laboratory-based prospective design. From a total of 376 positive blood cultures, 147 multidrug-resistant (MDR) organisms were identified, and 100 were randomly selected for final analysis. Susceptibility testing via disk diffusion and minimum inhibitory concentration (MIC) determination was performed to evaluate CZA efficacy. Results Klebsiella pneumoniae (K. pneumoniae) was the predominant (78%) organism among the subsets, with varying susceptibility patterns observed across species. The overall CZA susceptibility was 45%, with significant discrepancies between disk diffusion and gold standard testing. Notably, there was limited efficacy against Pseudomonas aeruginosa (P. aeruginosa) Conclusions This study underscores the pressing need for reliable testing methods and novel treatment strategies in combating MDR infections. Further research with larger sample sizes is imperative to validate our findings and guide clinicians effectively in addressing this critical health challenge.

Combinatorial Therapy: Targeting CD133+ Glioma Stem-like Cells with a Polysaccharide-Prodrug Complex Functionalised Gold Nanocages.

Cancer treatments are advancing to harness the body's immune system against tumours, aiming for lasting effects. This progress involves combining potent chemotherapy drugs with immunogens to kill cancer cells and trigger lasting immunity. Developing new prodrugs that integrate both chemotherapy and immune-boosting elements could significantly improve anticancer outcomes by activating multiple mechanisms to kill cancer cells. While bacterial polysaccharides are typically not used in therapy due to their immune-stimulating properties, we propose a safe application of an extremophilic bacterial polysaccharide, Mauran (MR), modified with the anticancer drug 5-fluorouracil (5FU) to create a novel prodrug. This obtained prodrug, chloracetyl-MR-5FU, is specifically targeted using gold nanocages to CD133+ glioma cells. Test results have shown a high encapsulation efficiency of the drug during the polysaccharide modification process; its anticancer activity was demonstrated in vitro and the release of the prodrug was demonstrated in ex vivo studies.

Advanced microscopic evaluation of parallel type I and type II cell deaths induced by multi-functionalized gold nanocages in breast cancer.

Despite aggressive surgical resections and combinatorial chemoradiations, certain highly malignant populations of tumor cells resurrect and metastasize. Mixed-grade cancer cells fail to respond to standard-of-care therapies by developing intrinsic chemoresistance and subsequently result in tumor relapse. Macroautophagy is a membrane trafficking process that underlies drug resistance and tumorigenesis in most breast cancers. Manipulating cellular homeostasis by a combinatorial nanotherapeutic model, one can evaluate the crosstalk between type I and type II cell death and decipher the fate of cancer therapy. Here, we present a multi-strategic approach in cancer targeting to mitigate the autophagic flux with subcellular toxicity via lysosome permeation, accompanied by mitochondrial perturbation and apoptosis. In this way, a nanoformulation is developed with a unique blend of a lysosomotropic agent, an immunomodulating sulfated-polysaccharide, an adjuvant chemotherapeutic agent, and a monoclonal antibody as a broad-spectrum complex for combinatorial nanotherapy of all breast cancers. To the best of our knowledge, this manuscript illustrates for the first time the applications of advanced microscopic techniques such as electron tomography, three-dimensional rendering and segmentation of subcellular interactions, and fate of the multifunctional therapeutic gold nanocages specifically targeted toward breast cancer cells.

Gold nanocages entering into the realm of high-contrast photoacoustic ocular imaging.

Bioinert gold nanoparticles of various shapes and functionalities are widely accepted as contrast agents (CAs) for several modalities of imaging, viz., electron microscopy, computerized tomography (CT), X-ray and photoacoustic (PA) imaging. However, testing of novel compact-imaging probes for ocular diagnostic imaging is always challenging. Here, ultra-fast microwave oven synthesized gold nanocages (AuNcgs) were successfully demonstrated for high-contrast PA ocular imaging for the first time. Methods are described for the synthesis, characterization and application of quickly synthesized AuNcgs in diagnostic ocular imaging. PA and ultrasound (US) images were acquired using a commercial US imaging scanner integrated with a tunable nanosecond pulsed laser. This integrated hybrid-modality system is a combined PA and US platform for imaging which enabled acquiring of complementary structural and optical absorption-based information simultaneously. Initial experiments were conducted using tubings filled with solutions of different concentrations of quickly synthesized AuNcgs. Biological PA and US imagings were demonstrated using enucleated porcine eye samples. Based on the acquired results, it is envisaged that AuNcgs can be employed as a high strength PA CA to potentially diagnose ocular disease like uveal melanoma in the near future.

Bioactive bacterial cellulose sulfate electrospun nanofibers for tissue engineering applications.

Cellulosic materials have been of tremendous importance to mankind since its discovery due to its superior properties and its abundance in nature. Recently, an increase in demand for alternate green materials has rekindled the interest for cellulosic materials. Here, bacterial cellulose has been functionalized with sulfate groups through acetosulfation to gain solubility in aqueous media, which provides access to several applications. The cell viability, antioxidant, and hemocompatibility assays have verified the biocompatible and antioxidant characteristics of bacterial cellulose sulfate (BCS) in both in vitro and ex vivo conditions. Further, novel BCS/polyvinyl alcohol nanofibers were fabricated by simple electrospinning route to engineer ultrafine nanoscale fibers. The biological evaluation of BCS/polyvinyl alcohol nanofiber scaffolds was done using L929 mouse fibroblast cells, which confirmed that these nanofibers are excellent matrices for cell adhesion and proliferation.

Formulation, characterization and evaluation of morusin loaded niosomes for potentiation of anticancer therapy.

Morusin, a water-insoluble prenylated flavonoid is known for its numerous medicinal properties. It manifests its anticancer potential by suppression of genes involved in tumor progression. However, poor solubility of the drug results in low bioavailability and rapid degradation thus hindering its clinical utilization. In order to overcome this, we have synthesized a niosome system composed of non-ionic surfactant span 60 and cholesterol using a thin-layer evaporation technique to improve the aqueous-phase solubility of the drug. Highly cytocompatible niosomes of 479 nm average size with smooth and uniform spherical morphology were synthesized in a facile manner. Unlike free morusin, nanomorusin was found to be freely dispersible in aqueous media. Having an extremely high drug entrapment efficiency (97%), controlled and sustained release of morusin resulting in enhanced therapeutic efficacy was observed in cancer cell lines of 4 different lineages. The results demonstrate that the morusin-niosome system is a promising strategy for enhanced anti-cancer activity against multiple cancer types and could be an indispensable tool for future targeted chemotherapeutic strategies.

Smart Carriers and Nanohealers: A Nanomedical Insight on Natural Polymers.

Biodegradable polymers are popularly being used in an increasing number of fields in the past few decades. The popularity and favorability of these materials are due to their remarkable properties, enabling a wide range of applications and market requirements to be met. Polymer biodegradable systems are a promising arena of research for targeted and site-specific controlled drug delivery, for developing artificial limbs, 3D porous scaffolds for cellular regeneration or tissue engineering and biosensing applications. Several natural polymers have been identified, blended, functionalized and applied for designing nanoscaffolds and drug carriers as a prerequisite for enumerable bionano technological applications. Apart from these, natural polymers have been well studied and are widely used in material science and industrial fields. The present review explains the prominent features of commonly used natural polymers (polysaccharides and proteins) in various nanomedical applications and reveals the current status of the polymer research in bionanotechnology and science sectors.

Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation.

Heat Shock Protein 90 (Hsp90) has been extensively explored as a potential drug target for cancer therapies. 17- N-allylamino- 17-demethoxygeldanamycin (17AAG) was the first Hsp90 inhibitor to enter clinical trials for cancer therapy. However, native drug is being shown to have considerable anticancer efficacy against pancreatic cancer when used in combination therapy regime. Further, magnetic hyperthermia has shown to have promising effects against pancreatic cancer in combination with known cyto-toxic drugs under both target and non-targeted scenarios. Hence, in order to enhance the efficacy of 17AAG against pancreatic cancer, we developed poly (lactic-co-glycolic acid) (PLGA) coated, 17AAG and Fe3O4 loaded magnetic nanoparticle formulations by varying the relative concentration of polymer. We found that polymer concentration affects the magnetic strength and physicochemical properties of formulation. We were also able to see that our aqueous dispensable formulations were able to provide anti-pancreatic cancer activity for MIA PaCa-2 cell line in dose and time dependent manner in comparison to mice fibroblast cell lines (L929). Moreover, the in-vitro magnetic hyperthermia against MIA PaCa-2 provided proof principle that our 2-in-1 particles may work against cancer cell lines effectively.

Extremophilic polysaccharide nanoparticles for cancer nanotherapy and evaluation of antioxidant properties.

Polysaccharides that show finest bioactivities and physicochemical properties are always promising for bionanoscience applications. Mauran is such a macromolecule extracted from halophilic bacterium, Halomonas maura for biotechnology and nanoscience applications. Antioxidant properties of MR/CH nanoparticles were studied using biochemical assays to prove the versatility of these test nanoparticles for biomedical applications. Here, we demonstrate the prospects of extremophilic polysaccharide, mauran based nanoparticles for scavenging reactive oxygen species in both in vitro and ex vivo conditions. 5-fluorouracil loaded MR/CH nanoparticles were tested for anticancer proliferation and compared their therapeutic efficiency using breast adenocarcinoma and glioma cells. Fluorescently labeled nanoparticles were employed to show the cellular uptake of these nanocarriers using confocal microscopic imaging and flow cytometry.

In vitro evaluation of antioxidant defense mechanism and hemocompatibility of mauran.

Mauran (MR), a highly polyanionic sulfated exopolysaccharide was extracted from moderately halophilic bacterium; Halomonas maura and characterized using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Purified MR was evaluated for antioxidant defense mechanisms under in vitro conditions using L929, mouse fibroblast cell line and mice liver homogenate. It was demonstrated that MR could impart protective effect against oxidative stress in both cells and tissue up to a concentration of 500 µg, which is found to be safe under laboratory conditions. Various enzymatic and non-enzymatic parameters of antioxidant mechanisms were evaluated and concluded that MR has the tendency to maintain a balance of antioxidative enzymes with in the test systems studied. Also, hemocompatibility assay performed revealed that MR has a lesser hemolytic index and exhibited a prolonged clotting time, which shows both antihemolytic, and antithrombogenic nature respectively. Furthermore, absorption studies performed using fluorescent-labeled MR confirmed that MR accumulated within the cell cytoplasm neither induced cellular lysis nor affected the cell integrity.

Biocompatible nanofibers based on extremophilic bacterial polysaccharide, Mauran from Halomonas maura.

Extremophilic bacterial polysaccharide based biocompatible nanofibers were produced for the first time via electrospinning technique. Mauran (MR), an extremophilic sulfated exopolysaccharide was extracted from moderately halophilic bacterium, Halomonas maura and characterized for the application of nanofiber synthesis. Thin-uniform MR nanofibers were produced using homogenous solutions of poly (vinyl alcohol) (PVA) blended with different concentrations of MR. Characterization of complex MR/PVA nanofibers were performed using scanning electron microscope and analyzed for the cytotoxicity using mouse fibroblast cells as well as mesenchymal stem cells. An average of 120 nm sized nanofibers were produced and tested for an enhanced cell growth under in vitro conditions in comparison with control. MR and MR/PVA nanofibers were found to be an excellent biomaterial for the migration, proliferation and differentiation of mammalian cells, which was confirmed by cell adhesion studies and confocal microcopy. Interestingly, biological and physicochemical properties of MR hasten the application of MR based nanofibers for various biomedical applications like tissue engineering and drug delivery.

Pharmaceutically versatile sulfated polysaccharide based bionano platforms.

Sulfated polysaccharides are complex polysaccharide molecules with excellent physico-chemical properties and bioactivities. On the basis of origin, they are classified as plant, animal, microbial and chemically synthesized sulfated polysaccharides. They have been widely applied in the fields of material and biological sciences. Biocompatibility and biodegradability of these molecules facilitate their increased use in the nanoparticle synthesis and tissue engineering applications. This review focuses on the structure, function and applications of important types of natural and chemically derived sulfated polysaccharides in the fields of nanotechnology and biomedical sciences. In the first part, we discuss the classification and role of sulfated polysaccharides in various fields. Later, we elaborate the specific bionano applications of commercially important sulfated polysaccharides in ionic gelation, stabilizing, cross-linking, capping and encapsulation of drugs. Finally, we conclude with the future scope and advanced applications of sulfated polysaccharides in various fields of interdisciplinary science. FROM THE CLINICAL EDITOR: This comprehensive review focuses on the structure, function, and applications of natural and chemically derived sulfated polysaccharides in the fields of nanotechnology and biomedical sciences.

Bacterial exopolysaccharide based nanoparticles for sustained drug delivery, cancer chemotherapy and bioimaging.

Introduction of a novel biocompatible, stable, biomaterial for drug delivery application remains always challenging. In the present study, we report the synthesis of an extremophilic bacterial sulfated polysaccharide based nanoparticle as a stable biocompatible material for drug delivery, evaluation of anticancer efficacy and bioimaging. Mauran (MR), the sulfated exopolysaccharide extracted from a moderately halophilic bacterium, Halomonas maura was used for the synthesis of nanoparticles along with chitosan (CH). MR/CH nanoparticles were synthesized by simple polyelectrolyte complexation of anionic MR and cationic CH. The MR/CH hybrid nanoparticles formed were ranging between 30 and 200 nm in diameter with an overall positive zeta potential of 27.5±5 mV and was found to be stable under storage in solution for at least 8 weeks. In vitro drug release studies showed a sustained and prolonged delivery of 5-fluorouracil (5FU) for 10-12 days from MR/CH nanoparticles under three different pHs of 4.5, 6.9 and 7.4 respectively. Cytotoxicity assay revealed that MR/CH nanoparticles were non-cytotoxic towards normal cells and toxic to cancer cells. Also, 5FU loaded MR/CH nanoparticles were found more effective than free 5FU in its sustained and controlled manner of killing breast adenocarcinoma cells. Fluorescein isothiocyanate (FITC) labeled MR/CH nanoparticles were used for cell binding and uptake studies; thereby demonstrating the application of dye tagged MR/CH nanoparticles for safe and nontoxic mode of live cellular imaging. We report the introduction of an extremophilic bacterial polysaccharide, MR, for the first time as a novel biocompatible and stable biomaterial to the world of nanotechnology, pharmaceutics and biomedical technology.

PEG coated biocompatible cadmium chalcogenide quantum dots for targeted imaging of cancer cells.

Cancer stands as a leading cause of mortality worldwide and diagnostics of cancer still faces drawbacks. Optical imaging of cancer would allow early diagnosis, evaluation of disease progression and therapy efficiency. To that aim, we have developed highly biocompatible PEG functionalized cadmium chalcogenide based three differently luminescent quantum dots (QDs) (CdS, CdSe and CdTe). Folate targeting scheme was utilized for targeting cancer cell line, MCF-7. We demonstrate the biocompatibility, specificity and efficiency of our nanotool in detection of cancer cells sparing normal cell lines with retained fluorescence of functionalized QDs as parental counterpart. This is the first time report of utilizing three differently fluorescent QDs and we have detailed about the internalization of these materials and time dependent saturation of targeting schemes. We present here the success of utilizing our biocompatible imaging tool for early diagnosis of cancer.