Rifampicin Lipid-Polymer hybrid nanoparticles (LIPOMER) for enhanced Peyer's patch uptake
Rifampicin Lipid-Polymer hybrid nanoparticles (LIPOMER) for enhanced Peyer's patch uptake
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DOI：
10.1016/j.ijpharm.2017.09.040
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发表时间：
2017-10-30
影响因子：
5.8
通讯作者：
Devarajan, Padma V.
中科院分区：
文献类型：
--
作者：
Bachhav, Sagar S.;Dighe, Vikas D.;Devarajan, Padma V.
完整纳米载体通过派尔集合淋巴结的口服摄取是重要的摄取途径。我们报告了利福平脂质-聚合物混合纳米粒（RIF-LIPOMER），其使用单硬脂酸甘油酯作为脂质和粘膜粘附聚合物Gantrez，目的是平衡疏水性和粘膜粘附，以增强派尔集合淋巴结吸收。使用Box-Behnken优化RIF-LIPOMER的大小、疏水性和粘膜粘附。设计的RIF-LIPOMER（RIF-LIPO-120）表现出在300-400 nm范围内的平均粒度，载药量> 12%。DSC和XRD证实完全非晶化。接触角和粘膜粘附力显示，与Gantrez纳米颗粒（RIF-GzNP）相比，RIF-LIPO-120表现出更大的疏水性和更低的粘膜粘附。在大鼠中十二指肠内施用后，通过派伊尔集合淋巴结对荧光标记的RIF-LIPO-120和RIF-GzNP的比较摄取揭示了RIF-GzNP在绒毛边缘处的高积累，以及RIF-LIPO-120的高派伊尔集合淋巴结摄取。此外，与RIF-GzNP相比，RIF-LIPO-120在肝脏中的较低积累表明门静脉循环的旁路和淋巴吸收通过派尔集合淋巴结。与RIF-GzNP相比，RIF-LIPO-120表现出的显著更高的肺：血浆浓度比证实了相同的结果（p < 0.05）。我们的研究表明，纳米颗粒的疏水性和粘膜粘附的优化可以有利于派伊尔斑吸收，这反过来可以增强药物在肺部的积累，在肺部疾病的治疗中具有优势。
The oral uptake of intact nanocarriers through Peyer's patches is an important uptake pathway. We report Rifampicin Lipid-Polymer hybrid nanoparticles (RIF-LIPOMER) using glyceryl monostearate as lipid and the mucoadhesive polymer, Gantrez, with the objective of balancing hydrophobicity and mucoadhesion for enhanced Peyer's patch uptake. RIF-LIPOMER was optimized for size, hydrophobicity, and mucoadhesion using Box-Behnken. Designed RIF-LIPOMER (RIF-LIPO-120) exhibited average particle size in the range 300-400 nm with drug loading >12%. DSC and XRD confirmed complete amorphization. Contact angle and mucoadhesion force revealed that RIF-LIPO-120 exhibited greater hydrophobicity and lower mucoadhesion compared to Gantrez nanoparticles (RIF-GzNP). Comparative uptake of fluorescent labelled RIF-LIPO-120 and RIF-GzNP, through Peyer's patch following intraduodenal administration in rats, revealed the high accumulation of RIF-GzNP at the villi border, and high Peyer's patch uptake of RIF-LIPO-120. Furthermore, lower accumulation of RIF-LIPO-120 in the liver, compared to RIF- GzNP, suggested bypass of the portal circulation and lymphatic uptake through Peyer's patches. Significantly higher lung: plasma concentration ratio exhibited by RIF-LIPO-120 compared to RIF-GzNP confirmed the same (p < 0.05). Our study demonstrated that optimization of hydrophobicity and mucoadhesion of nanoparticles could favor Peyer's patch uptake, which in turn could enable enhanced drug accumulation in the lungs with advantage in the therapy of pulmonary afflictions.