Intercalated theophylline-smectite hybrid for pH-mediated delivery

On the basis of their large specific surface areas, high adsorption and cation exchange capacities, swelling potential and low toxicity, natural smectite clays are attractive substrates for the gastric protection of neutral and cationic drugs. Theophylline is an amphoteric xanthine derivative that is widely used as a bronchodilator in the treatment of asthma and chronic obstructive pulmonary disease. This study considers the in vitro uptake and release characteristics of the binary theophylline-smectite system. The cationic form of theophylline was readily ion exchanged into smectite clay at pH 1.2 with a maximum uptake of 67±2 mg g−1. Characterisation of the drug-clay hybrid system by powder X-ray diffraction analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy confirmed that the theophylline had been exclusively intercalated into the clay system in an amorphous form. The drug remained bound within the clay under simulated gastric conditions at pH 1.2; and the prolonged release of approximately 40% of the drug was observed in simulated intestinal fluid at pH 6.8 and 7.4 within a 2-h timeframe. The incomplete reversibility of the intercalation process was attributed to chemisorption of the drug within the clay lattice. These findings indicate that smectite clay is a potentially suitable vehicle for the safe passage of theophylline into the duodenum. Protection from absorption in the stomach and subsequent prolonged release in the small intestine are advantageous in reducing fluctuations in serum concentration which may impact therapeutic effect and toxicit

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591