Transbuccal Delivery of CNS Therapeutic Nanoparticles: Synthesis, Characterization, and In Vitro Permeation Studies.
Transbuccal Delivery of CNS Therapeutic Nanoparticles: Synthesis, Characterization, and In Vitro Permeation Studies.
复制标题
中枢神经系统治疗性纳米颗粒的经颊递送：合成、表征和体外渗透研究。
DOI：
10.1021/cn200078m
复制
发表时间：
2011
影响因子：
5
通讯作者：
Yang,Hu
中科院分区：
文献类型：
--
作者：
Yuan,Quan;Fu,Yao;Kao,WeiyuanJohn;Janigro,Damir;Yang,Hu
本工作利用聚酰胺-胺（PAMAM）树枝状聚合物G4.5作为基础载体来构建中枢神经系统（CNS）治疗性纳米颗粒，并探索颊粘膜作为用于施用树枝状纳米颗粒的替代吸收位点。选择阿片肽DPDPE作为模型CNS药物。用聚乙二醇（PEG）将其偶联到PAMAM树状聚合物G4.5（即，PEG-G4.5-DPDPE）或用PEG和转铁蛋白受体单克隆抗体OX 26（即，0X26-PEG-G4.5-DPDPE）。利用猪颊粘膜固定的垂直Franz扩散池系统研究了5-氨基乙酰氨基荧光素（AAF）标记的治疗性树突状纳米粒的跨颊转运。为了比较，还测试了AAF标记的PAMAM树枝状聚合物G3.5和G4.5以及异硫氰酸荧光素（FITC）标记的G3.0和G4.0的经颊递送。PEG-G4.5（AAF）-DPDPE和OX 26-PEG-G4.5（AAF）-DPDPE的渗透性在10-7-10-6cm/s的数量级。胆盐甘氨脱氧胆酸钠（NaGDC）的共同管理增加了树突状纳米粒子的渗透性的倍数。类似地，由于粘膜粘附明胶/PEG半互穿网络（sIPN）的应用，树枝状纳米颗粒穿过猪颊粘膜的渗透性成倍增加。这些结果表明，经颊递送是用于施用CNS治疗性纳米颗粒的可能途径。
This work utilized polyamidoamine (PAMAM) dendrimer G4.5 as the underlying carrier to construct central nervous system (CNS) therapeutic nanoparticles and explored the buccal mucosa as an alternative absorption site for administration of the dendritic nanoparticles. Opioid peptide DPDPE was chosen as a model CNS drug. It was coupled to PAMAM dendrimer G4.5 with polyethylene glycol (PEG) (i.e., PEG-G4.5-DPDPE) or with PEG and transferrin receptor monoclonal antibody OX26 (i.e., OX26-PEG-G4.5-DPDPE). The therapeutic dendritic nanoparticles labeled with 5-(aminoacetamido) fluorescein (AAF) were studied for transbuccal transport using a vertical Franz diffusion cell system mounted with porcine buccal mucosa. For comparison, AAF-labeled PAMAM dendrimers G3.5 and G4.5 and fluorescein isothiocynate (FITC)-labeled G3.0 and G4.0 were also tested for transbuccal delivery. The permeability of PEG-G4.5 (AAF)-DPDPE and OX26-PEG-G4.5(AAF)-DPDPE were on the order of 10–7–10–6cm/s. Coadministration of bile salt sodium glycodeoxycholate (NaGDC) enhanced the permeability of dendritic nanoparticles by multiple folds. Similarly, a multifold increase of permeability of dendritic nanoparticles across the porcine buccal mucosal resulted from the application of mucoadhesive gelatin/PEG semi-interpenetrating network (sIPN). These results indicate that transbuccal delivery is a possible route for administration of CNS therapeutic nanoparticles.