A novel floating osmotic pump controlled release system （FOP） and traditional matrix sustained release tablets （MT） of dipyridamole （DIP） were characterized in terms of pharmacokinetics, drug release, and in vit...A novel floating osmotic pump controlled release system （FOP） and traditional matrix sustained release tablets （MT） of dipyridamole （DIP） were characterized in terms of pharmacokinetics, drug release, and in vitro-in vivo correlation. In vivo study was performed by a three-crossover study in six beagle dogs relative to the conventional tablet （CT）. A HPLC method for the determination of DIP in the plasma was developed. Cumulative percent of absorption fraction was compared to that of in vitro cumulative release. Both FOP and MT displayed obvious extended release characteristic in vivo while FOP showed a better extended release behavior. The bioavailability of FOP was higher than that of MT and a zero-order release linear correlation of DIP between fraction absorbed in vivo and fraction dissolved in vitro was established for FOP while not for MT. The results indicated the existence of an absorption window in upper part of the GI track of DIP, which meant that floating system could be excellent for the drug delivery. In addition, the in vitro model was a good choice for depicting in vivo absorption and for optimization of the formulation of FOP if it is needed to be bio-equivalent to MT.展开更多
Metabolic disorders are classified clinically as a complex and varied group of diseases including metabolic syndrome,obesity,and diabetes mellitus.Fat toxicity,chronic inflammation,and oxidative stress,which may chang...Metabolic disorders are classified clinically as a complex and varied group of diseases including metabolic syndrome,obesity,and diabetes mellitus.Fat toxicity,chronic inflammation,and oxidative stress,which may change cellular functions,are considered to play an essential role in the pathogenetic progress of metabolic disorders.Recent studies have found that cells secrete nanoscale vesicles containing proteins,lipids,nucleic acids,and membrane receptors,which mediate signal transduction and material transport to neighboring and distant cells.Exosomes,one type of such vesicles,are reported to participate in multiple pathological processes including tumor metastasis,atherosclerosis,chronic inflammation,and insulin resistance.Research on exosomes has focused mainly on the proteins they contain,but recently the function of exosome-associated microR NA has drawn a lot of attention.Exosomeassociated microR NAs regulate the physiological function and pathological processes of metabolic disorders.They may also be useful as novel diagnostics and therapeutics given their special features of non-immunogenicity and quick extraction.In this paper,we summarize the structure,content,and functions of exosomes and the potential diagnostic and therapeutic applications of exosome-associated micro RNAs in the treatment of metabolic disorders.展开更多
文摘A novel floating osmotic pump controlled release system （FOP） and traditional matrix sustained release tablets （MT） of dipyridamole （DIP） were characterized in terms of pharmacokinetics, drug release, and in vitro-in vivo correlation. In vivo study was performed by a three-crossover study in six beagle dogs relative to the conventional tablet （CT）. A HPLC method for the determination of DIP in the plasma was developed. Cumulative percent of absorption fraction was compared to that of in vitro cumulative release. Both FOP and MT displayed obvious extended release characteristic in vivo while FOP showed a better extended release behavior. The bioavailability of FOP was higher than that of MT and a zero-order release linear correlation of DIP between fraction absorbed in vivo and fraction dissolved in vitro was established for FOP while not for MT. The results indicated the existence of an absorption window in upper part of the GI track of DIP, which meant that floating system could be excellent for the drug delivery. In addition, the in vitro model was a good choice for depicting in vivo absorption and for optimization of the formulation of FOP if it is needed to be bio-equivalent to MT.
基金Project supported by the National Natural Science Foundation of China(Nos.81230018,81430020,81270869,81670796,and 81500595)
文摘Metabolic disorders are classified clinically as a complex and varied group of diseases including metabolic syndrome,obesity,and diabetes mellitus.Fat toxicity,chronic inflammation,and oxidative stress,which may change cellular functions,are considered to play an essential role in the pathogenetic progress of metabolic disorders.Recent studies have found that cells secrete nanoscale vesicles containing proteins,lipids,nucleic acids,and membrane receptors,which mediate signal transduction and material transport to neighboring and distant cells.Exosomes,one type of such vesicles,are reported to participate in multiple pathological processes including tumor metastasis,atherosclerosis,chronic inflammation,and insulin resistance.Research on exosomes has focused mainly on the proteins they contain,but recently the function of exosome-associated microR NA has drawn a lot of attention.Exosomeassociated microR NAs regulate the physiological function and pathological processes of metabolic disorders.They may also be useful as novel diagnostics and therapeutics given their special features of non-immunogenicity and quick extraction.In this paper,we summarize the structure,content,and functions of exosomes and the potential diagnostic and therapeutic applications of exosome-associated micro RNAs in the treatment of metabolic disorders.
