Introduction:
Heart rhythm disorders are major health issues that significantly increase the risk of cardiovascular complications. Atrial fibrillation plays a leading role, with a prevalence of 2–4%, and is expected to rise in the near future due to longer life expectancy and improved diagnostic methods. Amiodarone is a widely used antiarrhythmic drug. However, its application is limited by poor water solubility and severe side effects caused by its accumulation and off-target effects. Albumin-based nanoparticles are particularly attractive as macromolecular carriers because they are biodegradable, well tolerated by patients, and possess a high drug-loading capacity and strong binding affinity for many drugs. The aim of this study was to obtain albumin nanoparticles loaded with amiodarone and to investigate their physicochemical characteristics and release profile in phosphate buffer.

Methods:
Drug loading into albumin-based nanoparticles was performed via simple mixing in the presence of EtOH. Particles were purified by ultrafiltration and characterized. In vitro drug release studies were performed by dialysis at 37 °C in a phosphate buffer pH 7.4. The amiodarone content was determined spectrophotometrically at a wavelength of 260 nm (Spectramax and Nanodrop). The hydrodynamic size of the obtained particles was determined by Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) methods.

Results:
In the present study, loaded and unloaded bovine serum albumin particles were obtained by the desolvatation method using aqueous solutions of amiodarone and albumin by adding 96% EtOH. The resulting complexes were then cross-linked with 3,3' dithiobis (sulfosuccinimidyl) propionate. The hydrodynamic diameter of unloaded albumin particles was approximately 212 ± 5 nm (PDI 0.140) before the use of the cross-linking agent and 249 ± 17 nm (PDI 0.244) after cross-linking. The size of the amiodarone-loaded particles was 219 ± 1 nm (PDI 0.240) and 238 ± 6 nm (PDI 0.249) before and after cross-linking, respectively. The encapsulation efficiency, defined as the ratio of loaded amiodarone to the initial amount, was 36.8%. The loading capacity, calculated as the ratio of the loaded drug amount to the residual protein amount, was 30.6%. The in vitro release profile indicated that 55.8% of the drug was released within 48 hours, establishing developed albumin nanoparticles as the promising extended release platform.

Conclusions:
Thus, amiodarone-containing protein complexes based on albumin were obtained and characterized. The results demonstrate that these complexes can prolong the release of amiodarone, making them a promising platform for antiarrhythmic drug delivery.