Therapeutic efficacy of rifaximin loaded tamarind gum polysaccharide nanoparticles in TNBS induced IBD model Wistar rats.

BACKGROUND: Rifaximin is a non-systemic antibiotic used in the treatment of inflammatory bowel disease (IBD). Antibiotics are demonstrating a significant role in the treatment of IBD by altering the dysbiotic colonic microbiota and decreases the immunogenic and inflammatory response in the patient population. Mucoadhesive colon targeted nanoparticles provide the site-specific delivery and extended stay in the colon. Since the bacteria occupy the lumen, spread over the surface of epithelial cells, and adhere to the mucosa, delivering the rifaximin as a nanoparticles with the mucoadhesive polymer enhances the therapeutic efficacy in IBD. The objective was to fabricate and characterize the rifaximin loaded tamarind gum nanoparticles and study the therapeutic efficacy in the TNBS-induced IBD model rats. MATERIALS AND METHODS: The experimentation includes fabrication and characterization of drug excipient compatibility by FTIR. The fabricated nanoparticles were characterized for the hydrodynamic size and zeta potential by photon correlation spectroscopy and also analyzed by TEM. Selected best formulation was subjected to the therapeutic efficacy study in TNBS-induced IBD rats, and the macroscopic, microscopic and biochemical parameters were reported. RESULTS: The study demonstrated that the formulation TGN1 is best formulation in terms of nanoparticle characterization and hydrodynamic size which showed the hydrodynamic size of 171.4 nm and the zeta potential of -26.44 mV and other parameters such as TEM and drug release studies were also reported. CONCLUSIONS: The therapeutic efficacy study revealed that TGN1 is efficiently reduced the IBD inflammatory conditions as compared to the TNBS control group and reference drug mesalamine group.

ROS Modulating Inorganic Nanoparticles: A Novel Cancer Therapeutic Tool.

The term "reactive oxygen species" (ROS) refers to a family of extremely reactive molecules. They are crucial as secondary messengers in both physiological functioning and the development of cancer. Tumors have developed the ability to survive at elevated ROS levels with significantly higher H2O2 levels than normal tissues. Chemodynamic therapy is a novel approach to cancer treatment that generates highly toxic hydroxyl radicals via a Fenton/Fenton-like reaction between metals and peroxides. Inorganic nanoparticles cause cytotoxicity by releasing ROS. Inorganic nanoparticles can alter redox homoeostasis by generating ROS or diminishing scavenging mechanisms. Internalized nanoparticles generate ROS in biological systems independent of the route of internalisation. This method of producing ROS could be employed to kill cancer cells as a therapeutic strategy. ROS also play a role in regulating the development of normal stem cells, as excessive ROS disturb the stem cells' regular biological cycles. ROS treatment has a significant effect on normal cellular function. Mitochondrial ROS are at the centre of metabolic changes and control a variety of other cellular processes, which can lead to medication resistance in cancer patients. As a result, utilising ROS in therapeutic applications can be a double-edged sword that requires better understanding.

Inorganic nanoparticle-based advanced cancer therapies: Promising combination strategies.

Inorganic nanoparticles for drug delivery in cancer treatment offer many potential advantages because they can maximize therapeutic effect through targeting ligands while minimizing off-target side-effects through drug adsorption and infiltration. Although inorganic nanoparticles were introduced as drug carriers, they have emerged as having the capacity for combined therapeutic capabilities, including anticancer effects through cytotoxicity, suppression of oncogenes and cancer cell signaling pathway inhibition. The most promising advanced strategies for cancer therapy are as synergistic platforms for RNA interference (siRNA, miRNA, shRNA) and as synergistic drug delivery agents for the inhibition of cancer cell signaling pathways. The present work summarizes relevant current work, the promise of which is suggested by a projected compound annual growth rate of âˆ¼ 20% for drug delivery alone.

Anticancer therapeutic effect of cerium-based nanoparticles: known and unknown molecular mechanisms.

Cerium-based nanoparticles (CeNPs), particularly cerium oxide (CeO2), have been studied extensively for their antioxidant and prooxidant properties. However, their complete redox and enzyme-mimetic mechanisms of therapeutic action at the molecular level remain elusive, constraining their potential for clinical translation. Although the therapeutic effects of both antioxidant and prooxidant mechanisms generally are attributed to Ce3+ ↔ Ce4+ redox switching mediation, some studies have hinted at the involvement of unknown pathways in therapeutic effects. While redox switching is recognised increasingly as playing a key role in ROS-dependent cancer therapy, ROS-independent cytotoxicity mechanisms, such as Ce4+ dissolution and autophagy, also are emerging as being of importance. Although ROS-mediated prooxidant therapies are the most intensively studied, particularly in the context of cancer, the antioxidant activity deriving from the redox switching, particularly during radiation therapy, also plays an important role in the protection of normal cells during radiation therapy, hence reducing adverse effects. Since cancer cell proliferation results in aberrant behaviour of the tumour microenvironment (TME), then CeNP-based therapies are being used to address a multiplicity of known and unknown factors that aim to normalise the TME and thus prevent this aberrant behaviour. Although it is perceived that the pH plays a key role in the therapeutic performance of cerium-based nanoparticles, this is not conclusive because the relative importances of other factors, particularly Ce dissolution, Ce3+/Ce4+ ratio, cellular H2O2 level, and the role of anions, remain poorly understood. Consequently, the present work explores these multiple chemistry-driven mechanisms, which are both ROS-dependent and ROS-independent, in cancer therapy.

Cardioprotection by Citrus grandis (L.) Peel Ethanolic Extract in Alloxan-Induced Cardiotoxicity in Diabetic Rats.

Diabetic cardiomyopathy (DCM) pathogenesis is multifarious, and there are insufficient therapeutic options to treat DCM. The present research explored the effects of Citrus grandis peel ethanolic extract (CGPE) in alloxan-induced DCM in rats. Diabetes was triggered by intraperitoneal (i.p.) injection of alloxan (150 mg/kg) in Wistar rats (200-250 g). CGPE (100, 200, and 400 mg/kg) or glibenclamide (Glib, 10 mg/kg) were administered orally for 2 weeks. After the treatment schedule, prooxidants (thiobarbituric acid reactive substances), antioxidants (glutathione, catalase, and superoxide dismutase), and inflammatory markers (tumor necrosis factor-α) were determined in cardiac tissues. Biomarkers of cell death, viz., lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) activity, glucose levels, total cholesterol (TC), and high-density lipoproteins (HDL), were assessed in the blood. Rats administered with alloxan showed a consistent increase in blood glucose level (days 7 and 14) that was lowered considerably (p < 0.001) by CGPE or Glib. Alloxan-induced increase in LDH, CK-MB, TC, and decline in HDL was attenuated (p < 0.001) in rats that were treated with CGPE or Glib. Alloxan significantly (p < 0.001) elevated oxidative stress, inflammation, and reduced antioxidants in the cardiac tissue of rats, and these pathogenic abnormalities were ameliorated (p < 0.001) by CGPE. Histopathological studies showed a decrease in morphological disruptions by alloxan in CGPE-treated rats. CGPE (400 mg/kg) significantly ameliorated biochemical parameters in comparison to the lower doses against alloxan cardiotoxicity. Citrus grandis peel extract can be an alternative in the management of DCM.