Bachhav Sagar S, Dighe Vikas D, Kotak Darsheen, Devarajan Padma V
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai-400019, Maharashtra, India.
National Center for Preclinical Reproductive and Genetic Toxicology, ICMR-National Institute for Research in Reproductive Health (NIRRH), J.M. Street, Parel, Mumbai-400 012, India.
Int J Pharm. 2017 Oct 30;532(1):612-622. doi: 10.1016/j.ijpharm.2017.09.040. Epub 2017 Sep 19.
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 300-400nm 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.
完整纳米载体通过派尔集合淋巴结的口服摄取是一条重要的摄取途径。我们报道了以单硬脂酸甘油酯为脂质和黏附聚合物Gantrez的利福平脂质-聚合物杂化纳米颗粒（RIF-LIPOMER），目的是平衡疏水性和黏膜黏附性以增强派尔集合淋巴结摄取。使用Box-Behnken法对RIF-LIPOMER的尺寸、疏水性和黏膜黏附性进行了优化。设计的RIF-LIPOMER（RIF-LIPO-120）平均粒径在300 - 400nm范围内，载药量>12%。差示扫描量热法（DSC）和X射线衍射（XRD）证实完全非晶化。接触角和黏膜黏附力表明，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黏膜黏附性。在大鼠十二指肠内给药后，通过派尔集合淋巴结对荧光标记的RIF-LIPO-120和RIF-GzNP进行比较摄取，结果显示RIF-GzNP在绒毛边界高度积聚，而RIF-LIPO-120在派尔集合淋巴结摄取量高。此外，与RIF-GzNP相比，RIF-LIPO-120在肝脏中的积聚较低，提示绕过门静脉循环并通过派尔集合淋巴结进行淋巴摄取。RIF-LIPO-120与RIF-GzNP相比，肺与血浆浓度比显著更高，证实了这一点（p<0.05）。我们的研究表明，优化纳米颗粒的疏水性和黏膜黏附性有利于派尔集合淋巴结摄取，这反过来又可以使肺部药物积聚增加，在肺部疾病治疗中具有优势。
