Moscow Institute of Physics and Technology, 1А Kerchenskaya St, 117303, Moscow, Russia; Sirius University of Science and Technology, 1 Olimpiyskiy Ave, 354340, Sirius, Krasnodar region, Russia; Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilov St, 119991, Moscow, Russia.
Moscow Institute of Physics and Technology, 1А Kerchenskaya St, 117303, Moscow, Russia; Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilov St, 119991, Moscow, Russia.
Biochem Biophys Res Commun. 2024 Nov 19;734:150636. doi: 10.1016/j.bbrc.2024.150636. Epub 2024 Aug 31.
Injuries of the respiratory system caused by viral infections (e.g., by influenza virus, respiratory syncytial virus, metapneumovirus, or coronavirus) can lead to long-term complications or even life-threatening conditions. The challenges of treatment of such diseases have become particularly pronounced during the recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One promising drug is the anti-fibrinolytic and anti-inflammatory protease inhibitor aprotinin, which has demonstrated considerable inhibition of the replication of some viruses. Encapsulation of aprotinin in liposomes can significantly improve the effectiveness of the drug, however, the use of nanoparticles as carriers of aprotinin can radically change its biodistribution in the body. Here we show that the liposomal form of aprotinin accumulates more efficiently in the lungs, heart, and kidneys than the molecular form by side-by-side comparison of the ex vivo biodistribution of these two fluorescently labeled formulations in mice using bioimaging. In particular, we synthesized liposomes of different compositions and studied their accumulation in various organs and tissues. Direct comparison of the biodistributions of liposomal and free aprotinin showed that liposomes accumulated in the lungs 1.82 times more effectively, and in the heart and kidneys - 3.56 and 2.00 times, respectively. This suggests that the liposomal formulation exhibits a longer residence time in the target organ and, thus, has the potential for a longer therapeutic effect. The results reveal the great potential of the aprotinin-loaded liposomes for the treatment of respiratory system injuries and heart- and kidney-related complications of viral infections.
病毒感染引起的呼吸系统损伤（例如，流感病毒、呼吸道合胞病毒、副流感病毒或冠状病毒）可导致长期并发症甚至危及生命的情况。在由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)引起的最近一次大流行期间，这些疾病的治疗挑战变得尤为明显。一种有前途的药物是抗纤维蛋白溶解和抗炎蛋白酶抑制剂抑肽酶，它已证明对某些病毒的复制具有相当大的抑制作用。将抑肽酶包封在脂质体中可以显著提高药物的效果，然而，将纳米颗粒用作抑肽酶的载体可以彻底改变其在体内的生物分布。在这里，我们通过使用生物成像技术在小鼠中并排比较这两种荧光标记制剂的离体生物分布，证明了脂质体形式的抑肽酶比分子形式更有效地在肺部、心脏和肾脏中积累。特别是，我们合成了不同组成的脂质体，并研究了它们在各种器官和组织中的积累。脂质体和游离抑肽酶的生物分布的直接比较表明，脂质体在肺部的积累效率高 1.82 倍，在心脏和肾脏中的积累效率分别高 3.56 倍和 2.00 倍。这表明脂质体制剂在靶器官中具有更长的停留时间，因此具有更长的治疗效果的潜力。这些结果揭示了载有抑肽酶的脂质体在治疗呼吸系统损伤以及与病毒感染相关的心脏和肾脏并发症方面的巨大潜力。
