Targeted treatment of kidney using intravenous and intraarterial delivery of whey protein isolate-based microgels

被引:1
作者
Sindeeva, Olga A. [1 ]
Terentyeva, Daria A. [1 ,3 ]
Saveleva, Mariia S. [2 ]
Gusliakova, Olga I. [1 ,2 ]
Prikhozhdenko, Ekaterina S. [2 ]
Kulikov, Oleg A. [4 ]
Gorin, Dmitry A. [3 ]
Mayorova, Oksana A. [2 ]
机构
[1] Skolkovo Inst Sci & Technol, Vladimir Zelman Ctr Neurobiol & Brain Rehabil, 3 Nobel Str, Moscow 143005, Russia
[2] Saratov NG Chernyshevskii State Univ, Sci Med Ctr, 83 Astrakhanskaya St, Saratov 410012, Russia
[3] Skolkovo Inst Sci & Technol, Ctr Photon Sci & Engn, 3 Nobel Str, Moscow 143005, Russia
[4] Natl Res Ogarev Mordovia State Univ, 68 Bolshevistskaya Str, Saransk 430005, Russia
基金
俄罗斯科学基金会;
关键词
Intravenous/intraarterial injection; Target therapy; Whey protein isolate; Drug delivery system; Kidney; Fluorescent visualization; LIPID EMULSIONS; DRUG-DELIVERY; DISEASE; EXOCYTOSIS; STABILITY; IMPACT; SAFETY; ACID;
D O I
10.1016/j.optmat.2024.116043
中图分类号
T [工业技术];
学科分类号
08 ;
摘要
Here we report a promising whey protein isolate (WPI)-stabilized emulsion microgels for targeted drug delivery into the kidney. Investigation of stability revealed time-dependent degradation of the microgels starting at 72 h. Cytotoxicity studies showing increased sensitivity in Hek239 and Jurkat cells. A biodegradation assay underscored the role of macrophages in the destruction process of microgel particles. The efficiency of targeting the microgels for the kidney was assessed by biodistribution using intravenous and intraarterial delivery. Tail vein administration demonstrated long-term (minimum 5 days) selective accumulation not only in the liver but also in the kidneys. Renal artery injection of microgels resulted in an expected local increase in fluorescence in the target kidney in the first minutes after injection. In contrast, at 1 and 3 h there was an atypical accumulation of the Cy7 fluorescent signal in the opposite kidney. However, at 1 and 5 d the fluorescent signal predominated in the target kidney again and was higher in comparison with intravenous administration. Histological analysis validated the safety of WPI-based microgels using different methods of administration. By fine-tuning the physicochemical properties and delivery methods, the developed microgels offer an adjusted therapeutic approach with reduced side effects. They present new prospects for the treatment of kidney disorders using both intravenous administration and minimally invasive endovascular approach.
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页数:11
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