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Phan Thị Kiều Trang, Phạm Thu Uyên, Đỗ Thị Khánh Vy, Nguyễn Thành Dương(1)

NGHIÊN CỨU ỨNG DỤNG CHYLOMICRON TÀN DƯ TRONG HỆ VẬN CHUYỂN THUỐC TỚI GAN

APPLICATION OF CHYLOMICRON REMNANTS AS CARRIER FOR DRUG DELIVERY TO LIVER

Tạp chí Phân tích Hóa, Lý và Sinh học

2023

1

150

Chylomicrons (CM) are the largest lipid particles in the blood which consist largely of triglycerides. Chylomicron remnants (CMr) are formed when peripheral tissue lipids are removed from chylomicronsand bind to receptors on the surface of hepatocyte. Due to its properties, chylomicron remnants can serve as a great vehicle for drug delivery. This paper focuses on studying a three-component CMr -Toc - siRNA system, thereby improving the effectiveness of fatty liver disease treatments and reducing the effects unwanted side. The CMr – Toc – siRNA complexes were synthesized by lipophilic binding of the tocopherol residue of Toc-siRNA and CMr. The system was, then, tested for cytotoxicity by incubation with the Live/Dead assay kit and testing in mice to determine total RNA. According to research, chylomicron remnants have an average diameter of 140-143 nm determined by dynamic light scattering (DLS) measurement and contain apoB48 and apoE. With a cell viability of approximately 92.2%, the chylomicron remnant system carrying siRNA is highly biologically safe. Results from qRTPCR showed that CMr-Toc-siRNA was effective at delivering siRNA to liver cells via chylomicronmediated siRNA delivery, since endogenous apoB mRNA levels decreased by more than 30%.

Chylomicrons (CM) are the largest lipid particles in the blood which consist largely of triglycerides. Chylomicron remnants (CMr) are formed when peripheral tissue lipids are removed from chylomicronsand bind to receptors on the surface of hepatocyte. Due to its properties, chylomicron remnants can serve as a great vehicle for drug delivery. This paper focuses on studying a three-component CMr -Toc - siRNA system, thereby improving the effectiveness of fatty liver disease treatments and reducing the effects unwanted side. The CMr – Toc – siRNA complexes were synthesized by lipophilic binding of the tocopherol residue of Toc-siRNA and CMr. The system was, then, tested for cytotoxicity by incubation with the Live/Dead assay kit and testing in mice to determine total RNA. According to research, chylomicron remnants have an average diameter of 140-143 nm determined by dynamic light scattering (DLS) measurement and contain apoB48 and apoE. With a cell viability of approximately 92.2%, the chylomicron remnant system carrying siRNA is highly biologically safe. Results from qRTPCR showed that CMr-Toc-siRNA was effective at delivering siRNA to liver cells via chylomicronmediated siRNA delivery, since endogenous apoB mRNA levels decreased by more than 30%.