Magnetically responsive polymeric microparticles for oral delivery of protein drugs
Magnetically responsive polymeric microparticles for oral delivery of protein drugs
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DOI：
10.1007/s11095-005-9444-5
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发表时间：
2006-03-01
影响因子：
3.7
通讯作者：
Langer, RS
中科院分区：
文献类型：
--
作者：
Cheng, JJ;Teply, BA;Langer, RS
目的.蛋白质药物不能通过口服途径有效地递送。为了应对这一挑战，我们评估了在外部磁场存在下，延长胃肠道转运对磁响应微粒携带的胰岛素生物利用度的影响。将磁性纳米晶和胰岛素共包封在聚乳酸-乙醇酸共聚物（PLGA）微粒中，并在周向外加磁场的存在下评价其对小鼠低血糖的影响。对禁食小鼠单次给予100 U/kg的胰岛素-磁铁矿-PLGA微粒导致在存在外部磁场的情况下血糖水平降低高达43.8%，持续20小时（基于葡萄糖和ELISA测定，生物利用度分别= 2.77 +/- 0.46和0.87 +/- 0.29%），显著高于无磁场的相似剂量小鼠（基于葡萄糖和ELISA测定，生物利用度分别为0.66 +/- 0.56和0.30 +/-0.06%）。在存在外部磁场的情况下，在口服给予胰岛素-磁铁矿-PLGA微粒的小鼠中观察到显著改善的降血糖作用，这表明磁力可用于改善口服递送的蛋白质治疗剂的效率。
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.