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

Document Type : Original Article

Authors

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

7 Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

Abstract

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.

Keywords

Main Subjects


1. Choi YH, Han H-K. Nanomedicines: Current status and future perspectives in aspect of drug delivery and pharmacokinetics. J Pharm Investig 2018;48:43-60.
2. García-Pinel B, Porras-Alcalá C, Ortega-Rodríguez A, Sarabia F, Prados J, Melguizo C, et al. Lipid-based nanoparticles: Application and recent advances in cancer treatment. Nanomaterials 2019;9:638-660.
3. Ickenstein LM, Garidel P. Lipid-based nanoparticle formulations for small molecules and RNA drugs. Expert Opin Drug Deliv 2019;16:1205-1226.
4. Wang Q, Liu W, Wang J, Liu H, Chen Y. Preparation and pharmacokinetic study of Daidzein Long-circulating liposomes. Nanoscale Res Lett 2019;14:1-10.
5. Askarizadeh A, Butler AE, Badiee A, Sahebkar A. Liposomal nanocarriers for statins: A pharmacokinetic and pharmacodynamics appraisal. J Cell Physiol 2019;234:1219-1229.
6. Han B, Yang Y, Chen J, Tang H, Sun Y, Zhang Z, et al. Preparation, characterization, and pharmacokinetic study of a novel long-acting targeted paclitaxel liposome with antitumor activity. Int J Nanomedicine 2020;15:553-571.
7. Patel M, Sawant K. A quality by design concept on lipid based nanoformulation containing antipsychotic drug: Screening design and optimization using response surface methodology. J Nanomed Nanotechnol 2017;8:1-11.
8. Gonçalves L, Maestrelli F, Mannelli LDC, Ghelardini C, Almeida A, Mura P. Development of solid lipid nanoparticles as carriers for improving oral bioavailability of glibenclamide. Eur J Pharm Biopharm 2016;102:41-50.
9. Rampaka R, Ommi K, Chella N. Role of solid lipid nanoparticles as drug delivery vehicles on the pharmacokinetic variability of Erlotinib HCl. J Drug Deliv Sci Technol 2021;66:102886.
10. Koide H, Suzuki H, Ochiai H, Egami H, Hamashima Y, Oku N, et al. Enhancement of target toxin neutralization effect in vivo by PEGylation of multifunctionalized lipid nanoparticles. Biochem Biophys Res Commun 2021;555:32-39.
11. Aditya N, Macedo AS, Doktorovova S, Souto EB, Kim S, Chang P-S, et al. Development and evaluation of lipid nanocarriers for quercetin delivery: A comparative study of solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and lipid nanoemulsions (LNE). Food Sci Technol 2014;59:115-121.
12. Dolatabadi S, Karimi M, Nasirizadeh S, Hatamipour M, Golmohammadzadeh S, Jaafari MR. Preparation, characterization and in vivo pharmacokinetic evaluation of curcuminoids-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). J Drug Deliv Sci Technol 2021;62:102352.
13. Sodeifian G, Sajadian SA. Utilization of ultrasonic-assisted RESOLV (US-RESOLV) with polymeric stabilizers for production of amiodarone hydrochloride nanoparticles: Optimization of the process parameters. Chem Eng Res Des 2019;142:268-284.
14. Ahmed MS, Rodell CB, Hulsmans M, Kohler RH, Aguirre AD, Nahrendorf M, et al. A supramolecular nanocarrier for delivery of amiodarone anti-arrhythmic therapy to the heart. Bioconjug Chem 2019;30:733-740.
15. Buyuk N, Arayici P, Derman S, Mustafaeva Z, Yucel S. Synthesis of chitosan nanoparticles for controlled release of amiodarone. Indian J Pharm Sci  2020;82:131-138.
16. Motawea A, Ahmed DAM, Eladl AS, El-Mansy AAE-R, Saleh NM. Appraisal of amiodarone-loaded PLGA nanoparticles for prospective safety and toxicity in a rat model. Life Sci 2021;274:119344.
17. Lamprecht A, Bouligand Y, Benoit J-P. New lipid nanocapsules exhibit sustained release properties for amiodarone. J Control Release 2002;84:59-68.
18. Zhu Y, Wang M, Zhang J, Peng W, Firempong CK, Deng W, et al. Improved oral bioavailability of capsaicin via liposomal nanoformulation: Preparation, in vitro drug release and pharmacokinetics in rats. Arch Pharm Res 2015;38:512-521.
19. Ezekiel CI, Bapolisi AM, Walker RB, Krause RWM. Ultrasound-triggered release of 5-fluorouracil from soy lecithin echogenic liposomes. Pharmaceutics 2021;13:821-834.
20. Bhattacharyya S, Reddy P. Effect of surfactant on azithromycin dihydrate loaded stearic acid solid lipid nanoparticles. Turk J Pharm Sci 2019;16:425-431.
21. Khaleseh F, Barzegar-Jalali M, Zakeri-Milani P, Islambulchilar Z, Valizadeh H. Optimum surfactant concentration for preparation of amiodarone loaded solid lipid nanoparticles: Theoretical estimation versus experimental results by box-behnken design. J Rep Pharm Sci 2023;12:e146155.
22. Ragelle H, Crauste-Manciet S, Seguin J, Brossard D, Scherman D, Arnaud P, et al. Nanoemulsion formulation of fisetin improves bioavailability and antitumour activity in mice. Int J Pharm 2012;427:452-459.
23. Nikandish N, Hosseinzadeh L, Azandaryani AH, Derakhshandeh K. The role of nanoparticle in brain permeability: An in-vitro BBB model. Iran J Pharm Res 2016;15:403-414.
24. Alami-Milani M, Zakeri-Milani P, Valizadeh H, Salehi R, Jelvehgari M. Preparation and evaluation of PCL-PEG-PCL micelles as potential nanocarriers for ocular delivery of dexamethasone. Iran J Basic Med Sci 2018;21:153-164.
25. Agency EM. ICH Topic Q2 (R1) validation of analytical procedures: Text and methodology. Prescrire Int 1995;20:278.
26. Karami Z, Saghatchi Zanjani MR, Rezaee S, Rostamizadeh K, Hamidi M. Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: Remarkable brain delivery enhancement. Drug Dev Ind Pharm 2019;45:736-744.
27. Rodrigues M, Alves G, Ferreira A, Queiroz J, Falcão A. A rapid HPLC method for the simultaneous determination of amiodarone and its major metabolite in rat plasma and tissues: A useful tool for pharmacokinetic studies. J Chromatogr Sci 2013;51:361-370.
28. Soltani S, Jouyban A. A validated micellar LC method for simultaneous determination of furosemide, metoprolol and verapamil in human plasma. Bioanalysis 2012;4:41-48.
29. Zakeri-Milani P, Islambulchilar Z, Ghanbarzadeh S, Valizadeh H. Single dose bioequivalence study of two brands of olanzapine 10 mg tablets in Iranian healthy volunteers. Drug Res 2013;63: 346-350.
30. Soltani S, Jouyban A. Optimization and validation of an isocratic hplc-uv method for the simultaneous determination of five drugs used in combined cardiovascular therapy in human plasma. Asian J Chem 2011;23:1728-1734.
31. Karami Z, Sadighian S, Rostamizadeh K, Hosseini SH, Rezaee S, Hamidi M. Magnetic brain targeting of naproxen-loaded polymeric micelles: Pharmacokinetics and biodistribution study. Mater Sci Eng C Mater Biol Appl 2019;100:771-780.
32. Gülşah E-A, Selen İ, Akbaba H. Development and evaluation of solid witepsol nanoparticles for gene delivery. Turk J Pharm Sci 2021;18:344-351.
33. Shah M, Agrawal Y. Ciprofloxacin hydrochloride-loaded glyceryl monostearate nanoparticle: Factorial design of Lutrol F68 and Phospholipon 90G. J Microencapsul 2012; 29: 331-343.
34. Barzegar-Jalali M, Ghanbarzadeh S, Adibkia K, Valizadeh H, Bibak S, Mohammadi G, et al. Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers. BioImpacts 2014; 4:141.
35. Barzegar-Jalali M. Kinetic analysis of drug release from nanoparticles. J Pharm Pharm Sci 2008;11:167-177.
36. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010;67:217-223.
37. Wu IY, Bala S, Škalko-Basnet N, Di Cagno MP. Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes. Eur J Pharm Sci 2019;138:105026.
38. Thyagarajapuram N, Alexander K. A simplified method for the estimation of amiodarone hydrochloride by reverse‐phase high performance liquid chromatography. J Liquid Chromat Related Tech 2003;26:1315-1326.
39. Zolnik BS, Sadrieh N. Regulatory perspective on the importance of ADME assessment of nanoscale material containing drugs. Adv Drug Deliv Rev 2009;61:422-427.
40. Bewersdorff T, Glitscher EA, Bergueiro J, Eravci M, Miceli E, Haase A, et al. The influence of shape and charge on protein corona composition in common gold nanostructures. Mater Sci Eng C 2020;117:111270.
41. Wani TU, Raza SN, Khan NA. Nanoparticle opsonization: Forces involved and protection by long chain polymers. Polymer Bulletin 2020;77:3865-3889.
42. Rezwan K, Studart AR, Vörös J, Gauckler LJ. Change of ζ potential of biocompatible colloidal oxide particles upon adsorption of bovine serum albumin and lysozyme. J Phys Chem B 2005;109:14469-14474.
43. Bewersdorff T, Glitscher EA, Bergueiro J, Eravci M, Miceli E, Haase A, et al. The influence of shape and charge on protein corona composition in common gold nanostructures. Mater Sci Eng C Mater Biol Appl 2020;117:111270.
44. Janga KY, Jukanti R, Velpula A, Sunkavalli S, Bandari S, Kandadi P, et al. Bioavailability enhancement of zaleplon via proliposomes: Role of surface charge. Eur J Pharm Biopharm 2012;80:347-357.
45. Zhang X, Wang H, Ma Z, Wu B. Effects of pharmaceutical PEGylation on drug metabolism and its clinical concerns. Expert Opin Drug Toxicol 2014;10:1691-1702.
46. Ren H, He Y, Liang J, Cheng Z, Zhang M, Zhu Y, et al. Role of liposome size, surface charge, and PEGylation on rheumatoid arthritis targeting therapy. ACS Appl Mater Interfaces 2019;11:20304-20315.
47. Sadegh Malvajerd S, Azadi A, Izadi Z, Kurd M, Dara T, Dibaei M, et al. Brain delivery of curcumin using solid lipid nanoparticles and nanostructured lipid carriers: Preparation, optimization, and pharmacokinetic evaluation. ACS chem neuroscience. 2018;10:728-739.
48. Wani A, Savithra GHL, Abyad A, Kanvinde S, Li J, Brock S, et al. Surface PEGylation of mesoporous silica nanorods (MSNR): Effect on loading, release, and delivery of mitoxantrone in hypoxic cancer cells. Sci Rep 2017;7:2274-2284.
49. Shleghm MR, Mircioiu C, Voicu VA, Mircioiu I, Anuta V. Estimation of the in vivo release of amiodarone from the pharmacokinetics of its active metabolite and correlation with its in vitro release. Front Pharmacol 2021;11:621667-621675.
50. Gué E, Since M, Ropars S, Herbinet R, Le Pluart L, Malzert-Fréon A. Evaluation of the versatile character of a nanoemulsion formulation. Int J pharm 2016;498:49-65.
51. Takahama H, Shigematsu H, Asai T, Matsuzaki T, Sanada S, Fu HY, et al. Liposomal amiodarone augments anti-arrhythmic effects and reduces hemodynamic adverse effects in an ischemia/reperfusion rat model. Cardiovasc Drugs Ther 2013;27:125-132.
52. Zhuge Y, Zheng Z-F, Xie M-Q, Li L, Wang F, Gao F. Preparation of liposomal amiodarone and investigation of its cardiomyocyte-targeting ability in cardiac radiofrequency ablation rat model. Int J Nanomed 2016;11:2359-2367.
53. Patel A, Shelat P, Lalwani A. Development and optimization of solid self nanoemulsifying drug delivery (S-SNEDDS) using D-optimal design for improvement of oral bioavailability of amiodarone hydrochloride. Curr Drug Deliv. 2015;12:745-760.
54. Paek H-J, Lee Y-J, Chung H-E, Yoo N-H, Lee J-A, Kim M-K, et al. Modulation of the pharmacokinetics of zinc oxide nanoparticles and their fates in vivo. Nanoscale 2013;5:11416-11427.
55. Arnida M, Ray A, Peterson C, Ghandehari H. Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. Eur J Pharm Biopharm 2011;77:417-423.
56. Tiwari R, Pathak K. Nanostructured lipid carrier versus solid lipid nanoparticles of simvastatin: Comparative analysis of characteristics, pharmacokinetics and tissue uptake. Int J Pharm 2011;415:232-243.