How do lipid-based drug delivery systems affect the pharmacokinetic and tissue distribution of amiodarone? A comparative study of liposomes, solid lipid nanoparticles, and nanoemulsions
نویسندگان
1 Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
3 Pharmaceutical Sciences Research Center, Health Institute and School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
4 Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
5 Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
6 Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
doi
10.22038/ijbms.2024.75152.16292چکیده
Objective(s): Lipid-based drug delivery systems (DDS) can improve the pharmacokinetic (PK) parameters of some drugs. Especially those with a high volume of distribution (Vd) leading to off-target accumulation and toxicity. Amiodarone as an anti-arrhythmic agent induces hypothyroidism and liver disorders limiting its clinical indication.Materials and Methods: In the present study, amiodarone PK parameters and biodistribution after IV administration of four nano-formulations to rats were compared. The formulations were liposomes, solid lipid nanoparticles (SLN), PEGylated SLN (PEG-SLN), and nanoemulsions (NE). All formulations were optimized.Results: The nanoparticles were spherical with a diameter of 100-200 nm and sustained in vitro drug release in buffer pH 7.4. The best-fitted model for the plasma concentration-time profile was two-compartmental. In vivo studies indicated the most changes in PKs induced after liposome, SLN, and NE administration, respectively. The area under the curve (AUC) and maximum plasma concentration (Cmax) of liposomes, SLN, and NE were 22.5, 2.6, 2.46 times, and 916, 58, and 26 times higher than that of amiodarone solution, respectively (P-value<0.05). The heart-to-liver ratio of amiodarone was higher for nano-formulations compared to drug solution except for liposomes.Conclusion: Lipid-based particles can improve the PK parameters of amiodarone and its distribution in different tissues.
