Translational research : the journal of laboratory and clinical medicine
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Nanocarriers as drug delivery systems are promising and becoming popular, especially for cancer treatment. In addition to improving the pharmacokinetics of poorly soluble hydrophobic drugs by solubilizing them in a hydrophobic core, nanocarriers allow cancer-specific combination drug deliveries by inherent passive targeting phenomena and adoption of active targeting strategies. Nanoparticle-drug formulations can enhance the safety, pharmacokinetic profiles, and bioavailability of locally or systemically administered drugs, leading to improved therapeutic efficacy. ⋯ At present, the main barrier to implementing siRNA therapies in clinical practice is the lack of an effective delivery system that protects the siRNA from nuclease degradation, delivers to it to cancer cells, and releases it into the cytoplasm of targeted cancer cells, without creating adverse effects. This review provides an overview of various nanocarrier formulations in both research and clinical applications with a focus on combinations of siRNA and chemotherapeutic drug delivery systems for the treatment of multidrug resistant cancer. The use of various nanoparticles for siRNA-drug delivery, including liposomes, polymeric nanoparticles, dendrimers, inorganic nanoparticles, exosomes, and red blood cells for targeted drug delivery in cancer is discussed.
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The onset of vascular impairment precedes that of diagnostic hyperglycemia in diabetic patients suggesting a vascular insult early in the course of metabolic dysfunction without a well-defined mechanism. Mounting evidence implicates adipose inflammation in the pathogenesis of insulin resistance and diabetes. It is not certain whether amelioration of adipose inflammation is sufficient to preclude vascular dysfunction in early stages of metabolic disease. ⋯ Two-week treatment with metformin or pioglitazone or switching to normal chow ameliorated adipose inflammation and vascular dysfunction. Localized perivascular adipose inflammation is sufficient to trigger vascular dysfunction early in the course of diabetes. Interfering with this inflammatory process reverses this early abnormality.
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Acute respiratory distress syndrome (ARDS), replacing the clinical term acute lung injury, involves serious pathophysiological lung changes that arise from a variety of pulmonary and nonpulmonary injuries and currently has no pharmacological therapeutics. RNA interference (RNAi) has the potential to generate therapeutic effects that would increase patient survival rates from this condition. It is the purpose of this review to discuss potential targets in treating ARDS with RNAi strategies, as well as to outline the challenges of oligonucleotide delivery to the lung and tactics to circumvent these delivery barriers.