Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeing and study their effects on rats
Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeing and study their effects on rats
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DOI：
10.1080/10717544.2017.1413447
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发表时间：
2018-01-01
期刊：
影响因子：
6
通讯作者：
Attia, Alshaimaa
中科院分区：
文献类型：
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作者：
Abdelmonem, Rehab;el Nabarawi, Mohamed;Attia, Alshaimaa
本研究的目的是将盐酸格拉司琼（GH）司潘生丁配制成粘膜粘附凝胶和冻干插入物，用于鼻内给药，以提高GH的生物利用度和脑靶向。Carpapol 934和羟丙甲纤维素被掺入鼻用凝胶（GHSpNG）中的GH弹性体中。以明胶和羟丙基甲基纤维素（HPMC）为骨架形成剂，甘氨酸为崩解保护剂，甘露醇为填充剂和甜味剂，制备了GH Spanillin冻干插入物（GHSpNI）。制备的GHSpNG的pH值测量，药物含量，流变学，并在体外药物释放进行了表征。制备的GHSpNI的药物含量，表面pH值，GH释放，和粘膜粘附的特点。对大鼠进行生物学研究，包括药代动力学研究和脑药物靶向效率维度（LC-MS/MS）。结果表明，凝胶剂和白色凝胶片呈触变性假塑性，pH值在生理范围内，凝胶剂和凝胶片的药物含量分别为89.9-98.6%和82.4-98.38%，GH释放迅速。生物学研究表明，C-max.与GH溶液IV给药相比，鼻内给药凝胶和插入物后脑和血浆中的AUC（0-）（6 h）更高。凝胶和插入物的高脑靶向效率（分别为199.3%，230%）和凝胶和插入物的直接鼻至脑转运（分别为49.8%，56.95%）证实了在鼻施用负载于鼻凝胶和插入物中的GH司匹林后存在GH的直接鼻至脑转运。GHSpNIs可以被认为是一种潜在的新型药物递送系统，旨在通过鼻腔给药途径而不是GHSpNGs进行脑靶向。
The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release. The prepared GHSpNIs were characterized for drug content, surface pH, GH release, and mucoadhesion. Biological investigations including pharmacokinetics studies and brain drug targeting efficiency dimensions were performed on rats (LC-MS/MS). The results showed thixotropic pseudoplastic gels and white insert with pH values in a physiological range, drug content (89.9-98.6%), (82.4-98.38%) for gel and insert, respectively and rapid release rate of GH. Biological studies showed that C-max. and AUC(0-)(6h) in brain and plasma after intranasal administration of gel and insert were higher compared to IV administration of GH solution. A high brain targeting efficiency (199.3%, 230%) for gel and insert, respectively and a direct nose to brain transport (49.8%, 56.95%) for gel and insert, respectively confirmed that there is a direct nose to brain transport of GH following nasal administration of GH spanlastic loaded in nasal gel and insert. GHSpNIs can be considered as potential novel drug delivery system intended for brain targeting via the nasal rout of administration than GHSpNGs.