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

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.

The Inhibition by Guanfu Base A of Neuropathic Pain Mediated by P2Y12 Receptor in Dorsal Root Ganglia

“…Satellite glial cells (SGCs) enwrap the dorsal root ganglia (DRG) neuronal soma. , P2Y 12 receptor is expressed in SGCs of DRG. ,, Guanfu base A (GFA) is an alkaloid extracted from the root of Aconitum coreanum. , Guanfu base A has been reported to exhibit antiarrhythmic and anti-inflammatory effects. A large amount of inflammatory cytokines are released in neuropathic pain conditions.…”

“…12,14,19 Guanfu base A (GFA) is an alkaloid extracted from the root of Aconitum coreanum. 20,26 Guanfu base A has been reported to exhibit antiarrhythmic and antiinflammatory effects. A large amount of inflammatory cytokines are released in neuropathic pain conditions.…”

Blocking effect of Guan-Fu Base A on human Na V 1.5 channels and the mutants expressed in Xenopus Laevis oocytes

“…Their topological placement can be viewed on Swissprot(http://ca.expasy.org/uniprot/).Structure basis for drug block by CryoEM 19 revealed that the binding of drugs to channels was affected by various factors such as amino acid charge, hydrophobic interaction, protein conformation, molecular structure of drugs, etc. GFA is one kind of the diterpenoid alkaloids, and the propylene glycol amine chain is the hydrophilic part of GFA and the underlying hydrophenanthrene ring is its hydrophobic part 20 (Fig. 7).…”

Research Progress on Natural Products’ Therapeutic Effects on Atrial Fibrillation by Regulating Ion Channels

“…In terms of antiarrhythmia, GFA is a kind of multichannel blocker, which mainly blocks sodium channels. GFA can not only restrain action potential amplitude (APA) and Vmax and prolong action potential duration and effective refractory period but also change unidirectional conduction block into bidirectional conduction block and reduce the occurrence of premature contraction and atrioventricular reentry [ 119 , 120 ].…”