这项工作的目的是探索新型吸收促进剂对盐酸纳美芬(NMF)鼻腔吸收的影响。首先,在大鼠体内研究了不同浓度,类型和药物浓度的吸收促进剂对NMF鼻腔吸收的影响。研究的吸收促进剂包括正十二烷基-β-D-麦芽糖苷(DDM),羟丙基-β-环糊精(HP-β-CD),和聚乙二醇(15)-羟基硬脂酸酯(Solutol®HS15)。同时,采用原位蟾蜍腭模型和大鼠鼻黏膜模型评价纤毛毒性。结果表明,所研究的所有吸收促进剂都能显著促进NMF的鼻腔吸收,但程度和趋势不同。其中,0.5%(w/v)的DDM增强作用最强,其次是0.5%(w/v)Solutol®HS15,0.25%(w/v)DDM,0.25%(w/v)Solutol®HS15,0.1%(w/v)Solutol®HS15,0.1%(w/v)DDM,和0.25%(w/v)HP-β-CD,绝对生物利用度为76.49%,72.14%,71.00%,69.46%,60.41%,59.42%,55.18%,分别。所有吸收增强剂在鼻纤毛毒性试验中都表现出良好的安全性。从增强效果和安全性的角度来看,我们认为DDM是一种有前途的鼻腔吸收增强剂。除了DDM,Solutol®HS15还可以促进NMF的鼻内吸收,这将为盐酸纳美芬鼻喷雾剂的开发提供另一种选择。
The purpose of this work is to explore the effects of novel absorption enhancers on the nasal absorption of nalmefene hydrochloride (NMF). First, the influence of absorption enhancers with different concentrations and types and drug concentrations on the nasal absorption of NMF was investigated in vivo in rats. The absorption enhancers studied include n-dodecyl-β-D-maltoside (DDM), hydroxypropyl-β-cyclodextrin (HP-β-CD), and polyethylene glycol (15)-hydroxy Stearate (Solutol®HS15). At the same time, the in situ toad palate model and rat nasal mucosa model were used to assess the cilia toxicity. The results showed that all the absorption enhancers investigated significantly promote the nasal absorption of NMF, but with different degrees and trends. Among them, the 0.5% (w/v) DDM had the strongest enhancement effect, followed by 0.5% (w/v) Solutol®HS15, 0.25% (w/v) DDM, 0.25% (w/v) Solutol®HS15, 0.1% (w/v) Solutol®HS15, 0.1% (w/v) DDM, and 0.25% (w/v) HP-β-CD, with absolute bioavailability of 76.49%, 72.14%, 71.00%, 69.46%, 60.41%, 59.42%, and 55.18%, respectively. All absorption enhancers exhibited good safety profiles in nasal ciliary toxicity tests. From the perspective of enhancing effect and safety, we considered DDM to be a promising nasal absorption enhancer. And in addition to DDM, Solutol®HS15 can also promote intranasal absorption of NMF, which will provide another option for the development of nalmefene hydrochloride nasal spray.