期刊
PHARMACEUTICAL RESEARCH
卷 23, 期 3, 页码 557-564出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-005-9444-5
关键词
insulin; magnetic particles; microparticles; oral delivery; protein drugs
Purpose. Protein drugs cannot be delivered efficiently through oral routes. To address this challenge, we evaluated the effect of prolonged gastrointestinal transit on the bioavailability of insulin carried by magnetically responsive microparticles in the presence of an external magnetic field. Methods. Magnetite nanocrystals and insulin were coencapsulated into poly(lactide-co-glycolide) (PLGA) microparticles and their effects on hypoglycemia were evaluated in mice in the presence of a circumferentially applied external magnetic field. Results. A single administration of 100 U/kg of insulin-magnetite-PLGA microparticles to fasted mice resulted in a reduction of blood glucose levels of up to 43.8% in the presence of an external magnetic field for 20 h (bioavailability = 2.77 +/- 0.46 and 0.87 +/- 0.29% based on glucose and ELISA assay, respectively), significantly higher than similarly dosed mice without a magnetic field (bioavailability 0.66 +/- 0.56 and 0.30 +/- 0.06%, based on glucose and ELISA assay, respectively). Conclusions. A substantially improved hypoglycemic effect was observed in mice that were orally administered with insulin-magnetite-PLGA microparticles in the presence of an external magnetic field, suggesting that magnetic force can be used to improve the efficiency of orally delivered protein therapeutics.
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