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Drug Delivery and Translational Research

, Volume 8, Issue 5, pp 1471–1482 | Cite as

Safety, heart specificity, and therapeutic effect evaluation of Guanfu base A-loaded solid nanolipids in treating arrhythmia

  • Fei Xiong
  • Kunliang Liu
  • Sha Liu
  • Jianjun Chen
  • Jinghan Liu
  • Hao WangEmail author
  • Ning GuEmail author
Original Article

Abstract

Guanfu base A·HCl (GFA·HCl) solution, approved by the China Food and Drug Administration (CFDA) in 2005, has been used in the treatment of arrhythmia. However, the poor targeting and absorption of GFA·HCl have severely affected its clinical application. In this study, a nanolipid-based, Guanfu base A (GFA) delivery system was designed to improve the deficiency of GFA·HCl and realize better clinical effect. The GFA-loaded solid nanolipids (GFASN) with a core/shell structure, composed of Poloxamer 188, lecithin, and medium-chain fatty acid, were prepared using a high-pressure homogenate emulsification method. Results showed that GFASN possessed well morphology and stability during the process of lyophilization and rehydration at 220–260 nm. Safety evaluation revealed that ear vein injection of GFASN (14 mg/kg) were safe enough and of good biocompatibility. More importantly, GFASN can better alleviate the arrhythmia of rats, especially in ventricular ectopia and ventricular tachycardia, than GFA·HCl solution. Pharmacokinetic behaviors and targeting evaluation in mice demonstrated that nanolipids can help GFA achieve longer circulation time in blood and better heart specificity. Collectively, these promising findings suggested that this kind of nanolipids was an ideal delivery carrier for GFA in the treatment of cardiovascular disease.

Keywords

Solid nanolipids Guanfu base A Anti-arrhythmia effect Heart specificity Target drug delivery 

Notes

Funding information

This project has been funded in part by the National Key Research and Development Program of China (2017YFA0205502), the National Natural Science Foundation of China (81473160), the National New Drug Innovation Program of China (2017ZX09309024), the National Key Research and Development Program of China (2017YFA0104301), the Basic Research Program of Jiangsu Province (Natural Science Foundation, No. BK20151422) and the Qing Lan Project. This work is also supported by the Collaborative Innovation Center of Suzhou Nano Science and Technology.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical EngineeringSoutheast UniversityNanjingChina
  2. 2.Collaborative Innovation Center of Suzhou Nano-Science and Technology, Suzhou Key Laboratory of Biomaterials and TechnologiesSuzhouChina
  3. 3.Department of Natural Medicinal ChemistryChina Pharmaceutical UniversityNanjingChina

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