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N,N,N-三甲基壳聚糖改性的基于亚麻籽油的黏膜黏附性神经纳米乳剂用于经鼻脑递药。

N,N,N‑trimethyl chitosan modified flaxseed oil based mucoadhesive neuronanoemulsions for direct nose to brain drug delivery.

机构信息

Industrial Pharmacy Laboratory, Department of Pharmaceutics, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425 405, Maharashtra, India.

Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur, 110 033, Maharashtra, India.

出版信息

Int J Biol Macromol. 2018 Dec;120(Pt B):2560-2571. doi: 10.1016/j.ijbiomac.2018.09.032. Epub 2018 Sep 8.

DOI:10.1016/j.ijbiomac.2018.09.032
PMID:30201564
Abstract

Here we fabricated flaxseed oil-based neuronanoemulsions (NNEs) which were further surface-modified with a mucoadhesive polymer, N,N,N‑trimethyl chitosan (TMC) to form mucoadhesive neuronanoemulsions (mNNEs). The NNEs were loaded with high partitioning ropinirole-dextran sulfate (ROPI-DS) nanoplex and fabricated using hot high-pressure homogenization (HPH) technique. NNEs were optimized using Central Composite experimental design. TMC modified mNNE have not been prepared yet for direct nose to brain drug delivery. Here, an objective to provide controlled drug release with prolonged residence on the nasal mucosa for the treatment of Parkinson's disease (PD) is at prime consideration. Enhanced brain targeting through BBB bypass drug delivery, improved therapeutic efficacy through enhanced retention of mNNE formulation over nasal mucosal membrane, reduced dose and frequency of administration, and safety were further expected outcomes of this experiment. The mNNE formulation was subjected to 6 month stability assessment. The mNNE formulation was administered to the Swiss albino mice model via intranasal route and both, the plasma and brain pharmacokinetics were estimated. The in vivo studies performed on mice exhibited high brain targeting efficiency of mNNE formulation through nose to brain delivery via olfactory pathway. The prepared intranasal mNNEs could be on the clinics, if investigated more for behavioral and neurotoxicity studies.

摘要

我们制备了基于亚麻籽油的神经纳米乳液(NNEs),并用一种具有黏膜黏附性的聚合物 N,N,N-三甲基壳聚糖(TMC)对其进行表面修饰,形成黏膜黏附性神经纳米乳液(mNNEs)。NNEs 被加载了高分配罗匹尼罗-硫酸葡聚糖(ROPI-DS)纳米复合物,并使用热高压匀质(HPH)技术制备。NNEs 采用中心组合实验设计进行了优化。TMC 修饰的 mNNE 尚未用于直接鼻腔给药的脑靶向递药。在这里,我们的主要目标是通过 BBB 旁路递药提供控释,延长药物在鼻黏膜上的停留时间,用于治疗帕金森病(PD)。此外,还期望增强药物透过鼻腔黏膜的保留能力,从而提高治疗效果,减少给药剂量和频率,并确保安全性。对 mNNE 制剂进行了 6 个月的稳定性评估。通过鼻腔途径将 mNNE 制剂施用于瑞士白化病小鼠模型,并对其进行了血浆和脑药代动力学评估。在小鼠体内进行的研究表明,通过嗅觉途径进行鼻脑递药的 mNNE 制剂具有很高的脑靶向效率。如果对其进行更多的行为学和神经毒性研究,这种制备的鼻腔内 mNNEs 有望应用于临床。

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