Evaluation of the effect of different nano-drug delivery systems on amiodarone pharmacokinetics

Abstract

Introduction: The pharmacokinetic (PK) parameters of drugs can be improved by preparation of drug delivery systems (DDSs). They also change drug distribution in body leading to drug accumulation in the target site. Purpose: This study was aimed to optimize and characterize lipid-based DDSs of amiodarone (AMI) to evaluate the in vivo parameters and biodistribution of drug after preparation of nano-carriers.Methods: Liposome, solid lipid nanoparticle (SLN), PEGylated SLN (PEG-SLN) and nanoemulsion (NE) were prepared by thin film hydration, hot homogenization and emulsification method, respectively. The nano-formulations were optimized and evaluated for size, size distribution, zeta potential, morphology, entrapment efficiency and in vitro drug release. AMI analysis and extraction from plasma was performed by a validated and fast HPLC method. In vivo studies were conducted on Sprague Dawley rats. The PK parameters of AMI nanoparticles were assessed and drug distribution to liver, spleen, heart and kidney was analyzed. Results: The nanoparticles were spherical, measuring between 100-200 nm in diameter, and -46.9 to +40.2 mV in surface charge. They demonstrated a prolonged AMI release in PBS with a pH of 7.4. The solvent-salt precipitation method yielded the highest AMI recovery% from plasma samples. The plasma concentration over time was accurately described by two-compartment model. The in vivo experiments showed that the PKs were most altered following the administration of liposomes, SLN, and NE, respectively. The AUC and Cmax for liposome, SLN, and NE were 22.5, 2.6, and 2.46 times and 916, 58, and 26 times greater than AMI solution, respectively (P-value < 0.05). AMI distribution after administration of drug solution was equal between different tissues while nano-formulations showed different distribution to tissues.Conclusion: AMI loading into lipid-based DDSs can be considered as an effective approach for improvement of PKs and drug distribution. The most changes in parameters were resulted by liposomes.