The limitations of conventional therapeutic drugs necessitate the importance of developing novel therapeutics to treat diverse diseases. Conventional drugs have poor blood circulation time and are not stable or compatible with the biological system. Nanomaterials, with their exceptional structural properties, have gained significance as promising materials for the development of novel therapeutics. Nanofibers with unique physiochemical and biological properties have gained significant attention in the field of health care and biomedical research. The choice of a wide variety of materials for nanofiber fabrication, along with the release of therapeutic payload in sustained and controlled release patterns, make nanofibers an ideal material for drug delivery research. Electrospinning is the conventional method for fabricating nanofibers with different morphologies and is often used for the mass production of nanofibers. This review highlights the recent advancements in the use of nanofibers for the delivery of therapeutic drugs, nucleic acids and growth factors. A detailed mechanism for fabricating different types of nanofiber produced from electrospinning, and factors influencing nanofiber generation, are discussed. The insights from this review can provide a thorough understanding of the precise selection of materials used for fabricating nanofibers for specific therapeutic applications and also the importance of nanofibers for drug delivery applications.
Aggressive and recurrent gynecological cancers are associated with worse prognosis and a lack of effective therapeutic response. Ovarian cancer (OC) patients are often diagnosed in advanced stages, when drug resistance, angiogenesis, relapse, and metastasis impact survival outcomes. Currently, surgical debulking, radiotherapy, and/or chemotherapy remain the mainstream treatment modalities; however, patients suffer unwanted side effects and drug resistance in the absence of targeted therapies. Hence, it is urgent to decipher the complex disease biology and identify potential biomarkers, which could greatly contribute to making an early diagnosis or predicting the response to specific therapies. This review aims to critically discuss the current therapeutic strategies for OC, novel drug-delivery systems, and potential biomarkers in the context of genetics and molecular research. It emphasizes how the understanding of disease biology is related to the advancement of technology, enabling the exploration of novel biomarkers that may be able to provide more accurate diagnosis and prognosis, which would effectively translate into targeted therapies, ultimately improving patients’ overall survival and quality of life.
Type 2 diabetes mellitus (T2DM) is a chronic and progressive hyperglycemic condition. Glucagon-like peptide-1 (GLP1) is an incretin secreted from pancreatic β-cells and helps to produce insulin to balance the blood glucose level without the risk of hypoglycemia. However, the therapeutic application of GLP1 is limited by its intrinsic short half-life and rapid metabolic clearance in the body. To enhance the antidiabetic effect of GLP1, we designed a human cysteine-modified IgG1-Fc antibody-mediated oral gene delivery vehicle, which helps to produce GLP1 sustainably in the target site with the help of increased half-life of the Fc-conjugated nanocarrier, protects GLP1 from acidic and enzymatic degradation in the gastrointestinal (GI) tract, uptakes and transports the GLP1 formulation through the neonatal Fc receptor (FcRn), and helps to release the GLP1 gene in the intestine. Our formulation could reduce the blood glucose from about an average of 320 mg/dL (hyperglycemic) to 150 mg/dL (normal blood glucose concentration) in diabetic mice, which is about 50% reduction of the total blood glucose concentration. GLP1 (500 μg) complexed with the IgG1-Fc carrier was proven to be the optimal dose for a complete reduction of hyperglycemic conditions in diabetic mice. A significant amount of insulin production and the presence of GLP1 peptide were observed in the pancreatic islets of oral GLP1 formulation-treated diabetic mice in immunohistochemistry analysis compared to nontreated diabetic mice. The orally given formulation was completely nontoxic according to the histopathology analysis of mice organ tissues, and no mice death was observed. Our antibody-mediated oral gene delivery system is a promising tool for various oral therapeutic gene delivery applications to treat diseases like diabetes.
BackgroundRecent epidemiological and experimental studies suggest that cadmium and diabetes-related hyperglycemia may act synergistically to worsen metabolic regulation. The present study aims to evaluate the potential effects of Enhydra fluctuans extract in diabetes and dyslipidemia in cadmium (CdCl2) induced- normal and type 2 diabetic model rats.MethodForty-eight Long-Evans rats were divided equally into the following six groups: Normal Control (N-C), Normal treated with CdCl2 (N-Cd), Normal treated with plant extract (N-P), Normal treated with both plant extract and CdCl2 (N-PCd), Diabetic treated with plant extract (DM-P) and Diabetic treated with both plant extract and CdCl2 (DM-PCd). Blood glucose and other biochemical parameters were estimated by the enzymatic colorimetric method. Histological analysis of liver and heart was done by the hematoxylin-eosin (H & E) method.ResultsTwenty-one days treatment of E. fluctuans extracts at a dose of 200 mg/kg significantly reduced blood glucose level in N-PCd and DM-PCd (p < 0.05), and DM-P (p < 0.01) group. The plant extract had no direct effects on total blood lipids but, it had beneficial effects on TG/HDL-C ratio in N-P and DM-PCd groups (p < 0.05). Cd induction significantly reduced body weight [(N-Cd, N-PCd, DM-PCd) (p < 0.01)], and induced liver [N-Cd (p < 0.05), N-PCd, p < 0.001] and renal impairment [N-Cd (p < 0.05)]. In bi-variate association, a significant positive correlation between serum glucose and SGPT (p < 0.05) as well as SGPT and TG/HDL ratio (p = 0.019) was found in DM-P and in the merged group. The histology of liver and heart showed severe damages including inflammation, nuclear pyknosis, loss of myocardial fibers, necrosis and fibrosis in the Cd treated groups compared to plant treated groups.ConclusionE. fluctuans seems to have potent antihyperglycemic effects in diabetes and Cd toxicity along with partial antidyslipidemic properties in euglycemic and diabetic rats. Our study suggests a novel oral antihyperglycemic agent in the present environmental context.
Herein, a bile acid-inspired triple padlock oral gene delivery platform is developed, facilitating the protection of the therapeutic gene from gastrointestinal degradation, selective intestinal accumulation through a bile acid-specific transporter, and transportation of pDNA NPs through the enterohepatic recycling system. This nonviral oral gene delivery nanoparticle exhibits excellent gene expression kinetics in in vitro, in vivo, and ex vivo studies. A single oral dose leads to maintaining normoglycemia for up to 7 days in three different diabetes mouse models and 14 days in diabetic monkeys. Also, the optimized dosage form can reduce nonfast blood glucose levels and hemoglobin A1C within a normal range from the last stage diabetes conditions with a reduction of weight gain from changes of food uptake behavior after treatment once weekly for 20 weeks. Taken together, the current findings could improve the current painful treatment experience of diabetics and thus improve their quality of life.
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