Folic acid functionalized nanoparticles for enhanced oral drug delivery.
Folic acid functionalized nanoparticles for enhanced oral drug delivery.
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DOI：
10.1021/mp2005388
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发表时间：
2012-07-02
影响因子：
4.9
通讯作者：
Panyam J
中科院分区：
文献类型：
--
作者：
Roger E;Kalscheuer S;Kirtane A;Guru BR;Grill AE;Whittum-Hudson J;Panyam J
对于生物利用度较差的药物，可通过聚合物纳米粒的包埋来增强其口服吸收。纳米粒包裹的药物的跨细胞转运，可能通过跨细胞作用，可能是纳米粒促进药物吸收的主要机制。我们假设，通过靶向肠道上皮细胞上表达的叶酸受体，可以进一步增加细胞对纳米颗粒的摄取和运输。本研究的目的是研究叶酸功能化对口服生物利用度较低的化疗药物紫杉醇纳米粒跨细胞转运的影响。采用界面活性辅助表面功能化技术制备了载紫杉醇的表面功能化聚(D，L-丙交酯-乙交酯)纳米粒。以Caco-2细胞单层为体外模型，研究了紫杉醇纳米粒的转运。Caco-2细胞高水平表达叶酸受体和药物外排蛋白P-糖蛋白。将紫杉醇包裹在PLGA纳米粒中，使Caco-2细胞的表观通透性(Papp)增加了5倍。叶酸功能化的纳米粒进一步增加了转运(与游离紫杉醇相比，转运增加了8倍)。共聚焦显微镜研究表明，叶酸功能化的纳米颗粒被细胞内化，纳米颗粒对紧密连接的完整性没有任何明显影响。综上所述，我们的研究表明，叶酸功能化纳米粒有可能促进口服生物利用度较差的药物的口服吸收。
The oral absorption of drugs that have poor bioavailability can be enhanced by encapsulation in polymeric nanoparticles. Transcellular transport of nanoparticle-encapsulated drug, possibly through transcytosis, is likely the major mechanism through which nanoparticles improve drug absorption. We hypothesized that the cellular uptake and transport of nanoparticles can be further increased by targeting the folate receptors expressed on the intestinal epithelial cells. The objective of this research was to study the effect of folic acid functionalization on transcellular transport of nanoparticle-encapsulated paclitaxel, a chemotherapeutic with poor oral bioavailability. Surface-functionalized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with paclitaxel were prepared by the interfacial activity assisted surface functionalization technique. Transport of paclitaxel-loaded nanoparticles was investigated using Caco-2 cell monolayers as an in vitro model. Caco-2 cells were found to express folate receptor and the drug efflux protein, p-glycoprotein, to high levels. Encapsulation of paclitaxel in PLGA nanoparticles resulted in a 5-fold increase in apparent permeability (Papp) across Caco-2 cells. Functionalization of nanoparticles with folic acid further increased the transport (8-fold higher transport compared to free paclitaxel). Confocal microscopic studies showed that folic acid-functionalized nanoparticles were internalized by the cells and that nanoparticles did not have any gross effects on tight junction integrity. In conclusion, our studies indicate that folic acid functionalized nanoparticles have the potential to enhance the oral absorption of drugs with poor oral bioavailability.
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影响因子：
10.8
作者：
Mathot, Frederic;Rieux, A. Des;Preat, V.
通讯作者：
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影响因子：
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载有 UEA I 的纳米粒子用于鼻内给药后的脑递送
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作者：
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作者：
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作者：
MAINCENT, P;DEVISSAGUET, JP;COUVREUR, P
通讯作者：
COUVREUR, P