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以凤凰木胶作为天然粘膜粘附聚合物的表面工程化纳米结构脂质载体用于盐酸昂丹司琼的高效鼻脑递送

Surface engineered nanostructured lipid carriers for efficient nose to brain delivery of ondansetron HCl using Delonix regia gum as a natural mucoadhesive polymer.

作者信息

Devkar Tejas B, Tekade Avinash R, Khandelwal Kishanchandra R

机构信息

Department of Pharmaceutics, Rajarshi Shahu College of Pharmacy and Research, Tathawade, Pune 411033, India.

Department of Pharmaceutics, Rajarshi Shahu College of Pharmacy and Research, Tathawade, Pune 411033, India.

出版信息

Colloids Surf B Biointerfaces. 2014 Oct 1;122:143-150. doi: 10.1016/j.colsurfb.2014.06.037. Epub 2014 Jul 2.

Abstract

The objective of this investigation was to fabricate ondansetron hydrochloride [OND] loaded mucoadhesive nanostructured lipid carriers [NLCs] for efficient delivery to brain through nasal route. Mucoadhesive NLCs thereby sustaining drug release for longer time in nasal cavity. NLCs were prepared by high pressure homogenization [HPH] technique using glycerol monostearate [GMS]; as solid lipid, Capryol 90; as liquid lipid, soya lecithin; as surfactant and poloxamer 188; as cosurfactant. In the fabrication of NLCs, Delonix regia gum [DRG], isolated from seeds of D. regia belonging to family fabiaceae was used as a mucoadhesive polymer. The NLCs were evaluated for particle size, morphology, drug-entrapment efficiency [%EE], mucoadhesive strength, in vitro drug release, histological examination, ex vivo permeation study, in vivo biodistribution and pharmacokinetic studies in the brain/blood following intravenous [i.v.] and intranasal [i.n.] administration. Particle size, PDI, Zeta potential was observed in the range of 92.28-135nm, 0.32-0.46, and -11.5 to -36.2 respectively. Prepared NLCs achieved thermodynamic stability, control release pattern with minor histopathological changes in sheep nasal mucosa. The significantly [P<0.05] higher values for selected batch was observed, when administered by i.n. route showed higher drug targeting efficiency [506%] and direct transport percentage [97.14%] which confirms the development of promising OND-loaded NLC for efficient nose-to-brain delivery.

摘要

本研究的目的是制备载有盐酸昂丹司琼[OND]的黏膜黏附性纳米结构脂质载体[NLCs],以通过鼻腔途径有效地将药物输送到脑部。黏膜黏附性NLCs可在鼻腔中长时间维持药物释放。使用单硬脂酸甘油酯[GMS]作为固体脂质、辛酸癸酸甘油三酯90[Capryol 90]作为液体脂质、大豆卵磷脂作为表面活性剂以及泊洛沙姆188作为助表面活性剂,通过高压均质[HPH]技术制备NLCs。在制备NLCs时,使用从豆科植物凤凰木种子中分离出的凤凰木胶[DRG]作为黏膜黏附性聚合物。对NLCs进行了粒径、形态、药物包封率[%EE]、黏膜黏附强度、体外药物释放、组织学检查、离体渗透研究、静脉内[i.v.]和鼻内[i.n.]给药后在脑部/血液中的体内生物分布和药代动力学研究。观察到粒径、多分散指数[PDI]、zeta电位分别在92.28 - 135nm、0.32 - 0.46和 - 11.5至 - 36.2的范围内。制备的NLCs实现了热力学稳定性、控释模式,且对绵羊鼻黏膜的组织病理学变化较小。当通过鼻内途径给药时,所选批次的数值显著[P<0.05]更高,显示出更高的药物靶向效率[506%]和直接转运百分比[

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