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尼氯硝唑载固体脂质纳米粒的制备:体外特性评价及体内比较评价。

Fabrication of Niclosamide loaded solid lipid nanoparticles: in vitro characterization and comparative in vivo evaluation.

机构信息

a Department of Pharmacy , University of Malakand , Chakdara , Pakistan.

b Nano-Biotech Group (IBD) , National Institute for Biotechnology and Genetic Engineering , Faisalabad , Pakistan.

出版信息

Artif Cells Nanomed Biotechnol. 2018 Dec;46(8):1926-1934. doi: 10.1080/21691401.2017.1396996. Epub 2017 Nov 7.

DOI:10.1080/21691401.2017.1396996
PMID:29113501
Abstract

Niclosamide (NCS) is an oral anthelminthic drug having low solubility and hence low bioavailability. Current investigation shows an approach to fabricate solid lipid nanoparticles (SLNs) of NCS and evaluated for pharmaceutical, in vitro and in vivo characterization. NFM-3 showed particle size 204.2 ± 2.2 nm, polydispersity index 0.328 ± 0.02 and zeta potential -33.16 ± 2 mV. Entrapment efficiency and drug loading capacity were 84.4 ± 0.02% and 5.27 ± 0.03%, respectively. Scanning electron microscopy image indicated that particles were nanoranged. DSC and P-XRD results showed change in physicochemical properties of NCS. FT-IR spectra confirmed compatibility between NCS and excipients. The drug release profile showed sustained release (93.21%) of NCS in 12 h. Different kinetic models showed zero-order kinetics and Case-II transport mechanism. Study showed maximum stability at refrigerated temperature. In vivo pharmacokinetic study showed 2.15-fold increase in NCS peak plasma concentration as solid lipid nanoparticle formulation (NFM-3) compared to commercial product while relative bioavailability was 11.08. Results including in vitro and in vivo release studies of NCS confirmed that SLNs system is suitable to improve oral delivery of NCS with increased aqueous solubility, permeability and finally bioavailability.

摘要

尼氯硝唑(NCS)是一种口服驱虫药,溶解度低,因此生物利用度也低。目前的研究表明,可以制备 NCS 的固体脂质纳米粒(SLNs),并对其进行药物、体外和体内特性评估。NFM-3 的粒径为 204.2 ± 2.2nm,多分散指数为 0.328 ± 0.02,zeta 电位为-33.16 ± 2mV。包封效率和载药量分别为 84.4 ± 0.02%和 5.27 ± 0.03%。扫描电子显微镜图像表明,颗粒呈纳米级。DSC 和 P-XRD 结果表明 NCS 的物理化学性质发生了变化。FT-IR 谱图证实了 NCS 与赋形剂之间的相容性。药物释放曲线表明 NCS 在 12 小时内呈现出持续释放(93.21%)。不同的动力学模型表明,零级动力学和二级传输机制。研究表明,在冷藏温度下,制剂具有最大的稳定性。体内药代动力学研究表明,与商业产品相比,NCS 固体脂质纳米粒(NFM-3)的峰值血浆浓度增加了 2.15 倍,而相对生物利用度为 11.08。包括 NCS 的体外和体内释放研究的结果证实,SLNs 系统适合提高 NCS 的口服递送,增加其水溶解度、渗透性,最终提高生物利用度。

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