Recent advances in buccal drug delivery and absorption - in vitro and in vivo studies
Recent advances in buccal drug delivery and absorption - in vitro and in vivo studies
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DOI：
10.1016/s0168-3659(99)00032-2
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发表时间：
1999-11-01
影响因子：
10.8
通讯作者：
Verhoef, JC
中科院分区：
文献类型：
--
作者：
Junginger, HE;Hoogstraate, JA;Verhoef, JC
在本研究的第一部分中，目的是表征不同分子量的异硫氰酸荧光素（FITC）标记的葡聚糖作为模型化合物的肽和蛋白质通过颊粘膜的运输。通过测量transbuccal通量和通过分析荧光探针在上皮中的分布，使用共聚焦激光扫描显微镜可视化渗透途径，研究了这些葡聚糖通过猪颊粘膜（非角化上皮，相当于人颊粘膜）的渗透。结果表明，亲水性化合物如FITC-葡聚糖通过猪颊上皮仅限于分子量低于20 kDa的渗透物。颊粘膜对4和10 kDa FITC-葡聚糖（10（-8）cm/s量级）的渗透性彼此之间或与小得多的化合物FITC之间没有显著差异。共聚焦图像的分布模式的FITC-葡聚糖表明，细胞旁的路线是通过颊上皮的主要途径。在本研究的体内部分，在猪体内研究了FITC标记的右旋糖酐4400（FD4）和肽类药物布舍瑞林的口腔给药。递送装置由具有FD 4或布舍瑞林溶液的施用室组成，并使用粘合贴片附着于颊粘膜4小时。在猪中进行了一项随机交叉研究，包括静脉给药和口腔给药，不使用和使用10 mM甘氨脱氧胆酸钠（GDC）作为吸收促进剂。口腔给药后，迅速达到稳态血浆水平。10 mM GDC的GO给药使FD4的绝对生物利用度从1.8 +/-0.5增加到12.7 +/-2.0%。从目前的研究中，可以得出结论，口腔给药是一个合适的途径，为大分子和亲水性化合物，如肽类药物的交付。(C)1999 Elsevier Science B.V.保留所有权利。
In the first part of this study, the aim was to characterize transport of fluorescein isothiocyanate (FITC)-labelled dextrans of different molecular weights as model compounds for peptides and proteins through buccal mucosa. The penetration of these dextrans through porcine buccal mucosa (a nonkeratinized epithelium, comparable to human buccal mucosa) was investigated by measuring transbuccal fluxes and by analyzing the distribution of the fluorescent probe in the epithelium, using confocal laser scanning microscopy for visualizing permeation pathways. The results revealed that passage of hydrophilic compounds such as the FITC-dextrans through porcine buccal epithelium is restricted to permeants with a molecular weight lower than 20 kDa. The permeabilities of buccal mucosa for the 4 and 10 kDa FITC-dextran (of the order of 10(-8) cm/s) were not significantly different from each other or from the much smaller compound FITC. The confocal images of the distribution pattern of FITC-dextrans showed that the paracellular route is the major pathway through buccal epithelium. In the in vivo part of this study, buccal delivery of FITC-labelled dextran 4400 (FD4) and the peptide drug buserelin was investigated in vivo, in pigs. The delivery device consisted of an application chamber with a solution of FD4 or buserelin, and was attached to the buccal mucosa for 4 h using an adhesive patch. A randomized cross-over study including intravenous administration and buccal delivery without and with 10 mM sodium glycodeoxycholate (GDC) as an absorption enhancer was performed in pigs. After buccal administration, steady-state plasma levels were rapidly achieved. Go-administration of 10 mM GDC increased the absolute bioavailability from 1.8+/-0.5 to 12.7+/-2.0% for FD4. From the present studies, it is concluded that buccal administration is a suitable route for the delivery for macromolecules and hydrophilic compounds such as peptide drugs. (C) 1999 Elsevier Science B.V. All rights reserved.