12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Improved i.p. drug delivery with bioadhesive nanoparticles.

      Proceedings of the National Academy of Sciences of the United States of America

      Proceedings of the National Academy of Sciences

      drug delivery, intraperitoneal, ovarian cancer, chemotherapy, nanoparticles

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The i.p. administration of chemotherapy in ovarian and uterine serous carcinoma patients by biodegradable nanoparticles may represent a highly effective way to suppress peritoneal carcinomatosis. However, the efficacy of nanoparticles loaded with chemotherapeutic agents is currently hampered by their fast clearance by lymphatic drainage. Here, we show that a unique formulation of bioadhesive nanoparticles (BNPs) can interact with mesothelial cells in the abdominal cavity and significantly extend the retention of the nanoparticles in the peritoneal space. BNPs loaded with a potent chemotherapeutic agent [epothilone B (EB)] showed significantly lower systemic toxicity and higher therapeutic efficacy against i.p. chemotherapy-resistant uterine serous carcinoma-derived xenografts compared with free EB and non-BNPs loaded with EB.

          Related collections

          Most cited references 38

          • Record: found
          • Abstract: found
          • Article: not found

          Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health.

          Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma.

            Current therapy for glioblastoma multiforme is insufficient, with nearly universal recurrence. Available drug therapies are unsuccessful because they fail to penetrate through the region of the brain containing tumor cells and they fail to kill the cells most responsible for tumor development and therapy resistance, brain cancer stem cells (BCSCs). To address these challenges, we combined two major advances in technology: (i) brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery and (ii) repurposed compounds, previously used in Food and Drug Administration-approved products, which were identified through library screening to target BCSCs. Using fluorescence imaging and positron emission tomography, we demonstrate that brain-penetrating nanoparticles can be delivered to large intracranial volumes in both rats and pigs. We identified several agents (from Food and Drug Administration-approved products) that potently inhibit proliferation and self-renewal of BCSCs. When loaded into brain-penetrating nanoparticles and administered by convection-enhanced delivery, one of these agents, dithiazanine iodide, significantly increased survival in rats bearing BCSC-derived xenografts. This unique approach to controlled delivery in the brain should have a significant impact on treatment of glioblastoma multiforme and suggests previously undescribed routes for drug and gene delivery to treat other diseases of the central nervous system.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Overcoming tumor multidrug resistance using drugs able to evade P-glycoprotein or to exploit its expression.

              Multidrug resistance (MDR) is a major obstacle to the effective treatment of cancer. Cellular overproduction of P-glycoprotein (P-gp), which acts as an efflux pump for various anticancer drugs (e.g. anthracyclines, Vinca alkaloids, taxanes, epipodophyllotoxins, and some of the newer antitumor drugs) is one of the more relevant mechanisms underlying MDR. P-gp belongs to the superfamily of ATP-binding cassette transporters and is encoded by the ABCB1 gene. Its overexpression in cancer cells has become a therapeutic target for circumventing MDR. As an alternative to the classical pharmacological strategy of the coadministration of pump inhibitors and cytotoxic substrates of P-gp and to other approaches applied in experimental tumor models (e.g. P-gp-targeting antibodies, ABCB1 gene silencing strategies, and transcriptional modulators) and in the clinical setting (e.g. incapsulation of P-gp substrate anticancer drugs into liposomes or nanoparticles), a more intriguing strategy for circumventing MDR is represented by the development of new anticancer drugs which are not substrates of P-gp (e.g. epothilones, second- and third-generation taxanes and other microtubule modulators, topoisomerase inhibitors). Some of these drugs have already been tested in clinical trials and, in most of cases, show relevant activity in patients previously treated with anticancer agents which are substrates of P-gp. Of these drugs, ixabepilone, an epothilone, was approved in the United States for the treatment of breast cancer patients pretreated with an anthracycline and a taxane. Another innovative approach is the use of molecules whose activity takes advantage of the overexpression of P-gp. The possibility of overcoming MDR using the latter two approaches is reviewed herein.  © 2011 Wiley Periodicals, Inc.
                Bookmark

                Author and article information

                Journal
                27663731
                5068292
                10.1073/pnas.1523141113

                Comments

                Comment on this article