Transepithelial transport of Fc-targeted nanoparticles by the neonatal fc receptor for oral delivery.
Transepithelial transport of Fc-targeted nanoparticles by the neonatal fc receptor for oral delivery.
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DOI：
10.1126/scitranslmed.3007049
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发表时间：
2013-11-27
影响因子：
17.1
通讯作者：
Farokhzad OC
中科院分区：
文献类型：
--
作者：
Pridgen EM;Alexis F;Kuo TT;Levy-Nissenbaum E;Karnik R;Blumberg RS;Langer R;Farokhzad OC
纳米颗粒有望对许多疾病的治疗产生巨大影响，但其广泛应用受到限制，因为目前它们只能通过肠胃外方法施用。纳米粒子的口服给药是优选的，但仍然是一个挑战，因为穿过肠上皮的转运是有限的。在这里，我们表明，利用体外和体内模型，靶向新生儿 Fc 受体 (FcRn) 的纳米颗粒可以有效地跨肠上皮转运，已知 FcRn 可以介导 IgG 抗体穿过上皮屏障的转运。在小鼠中，口服 FcRn 靶向纳米颗粒穿过肠上皮并到达体循环，平均吸收效率为 13.7%*h，而非靶向纳米颗粒的平均吸收效率仅为 1.2%*h。此外，含有胰岛素的靶向纳米颗粒作为基于纳米颗粒的糖尿病治疗模型，以 1.1 U/kg 的临床相关胰岛素剂量口服给药，并在野生型小鼠中引发了延长的低血糖反应。这种效应在 FcRn 敲除小鼠中被消除，表明纳米颗粒转运的增强是由 FcRn 引起的。 FcRn 靶向纳米颗粒可能对许多疾病的治疗产生重大影响，因为它使目前受低生物利用度限制的药物能够通过口服给药有效递送。
Nanoparticles are poised to have a tremendous impact on the treatment of many diseases, but their broad application is limited because currently they can only be administered by parenteral methods. Oral administration of nanoparticles is preferred but remains a challenge because transport across the intestinal epithelium is limited. Here, we show that nanoparticles targeted to the neonatal Fc receptor (FcRn), which is known to mediate the transport of IgG antibodies across epithelial barriers, are efficiently transported across the intestinal epithelium using both in vitro and in vivo models. In mice, orally administered FcRn-targeted nanoparticles crossed the intestinal epithelium and reached systemic circulation with a mean absorption efficiency of 13.7%*h compared with only 1.2%*h for non-targeted nanoparticles. In addition, targeted nanoparticles containing insulin as a model nanoparticle-based therapy for diabetes were orally administered at a clinically relevant insulin dose of 1.1 U/kg and elicited a prolonged hypoglycemic response in wild-type mice. This effect was abolished in FcRn knockout mice, indicating the enhanced nanoparticle transport was due specifically to FcRn. FcRn-targeted nanoparticles may have a major impact on the treatment of many diseases by enabling drugs currently limited by low bioavailability to be efficiently delivered though oral administration.
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影响因子：
8.4
作者：
Borner, MM;Schöffski, P;Fumoleau, P
通讯作者：
Fumoleau, P
DOI：
10.1089/jam.2005.18.294
发表时间：
2005-09-01
期刊：
JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG
影响因子：
--
作者：
Dumont, JA;Bitonti, AJ;Newman, SP
通讯作者：
Newman, SP
DOI：
10.1073/pnas.0601755103
发表时间：
2006-04-18
影响因子：
11.1
作者：
Farokhzad, OC;Cheng, JJ;Langer, R
通讯作者：
Langer, R
影响因子：
3.4
作者：
Armstrong, JK;Wenby, RB;Fisher, TC
通讯作者：
Fisher, TC
影响因子：
15.9
作者：
Dickinson, BL;Badizadegan, K;Lencer, WI
通讯作者：
Lencer, WI