Thermostable ionizable lipid-like nanoparticle (iLAND) for RNAi treatment of hyperlipidemia
On 16 February 2022, Yuanyu Huang, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Beijing Institute of Technology, and his team published a paper tittled “Thermostable ionizable lipid-like nanoparticle (iLAND) for RNAi treatment of hyperlipidemia” in SCIENCE ADVANCES, which established a thermostable clinically applicable delivery system for siRNA drug.
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Small interfering RNA (siRNA) therapeutic is considered to be a promising modality for the treatment of hyperlipidemia. Establishment of a thermostable clinically applicable delivery system remains a most challenging issue for siRNA drug development. Here, a series of ionizable lipid-like materials were rationally designed; 4 panels of lipid formulations were fabricated and evaluated on the basis of four representative structures. The lead lipid (A1-D1-5) was stable at 40°C, and the optimized formulation (iLAND) showed dose and time dual-dependent gene silencing pattern with median effective dose of 0.18 mg/kg. In addition, potent and durable reduction of serum cholesterol and triglyceride were achieved by administering siRNAs targeting angiopoietin-like 3 or apolipoprotein C3 (APOC3) in high-fat diet–fed mice, db/db mice, and human APOC3 transgenic mice, respectively, accompanied by displaying ideal safety profiles. Therefore, siRNA@iLAND prepared with thermostable A1-D1-5 demonstrates substantial value for siRNA delivery, hyperlipidemia therapy, and prevention of subsequent metabolic diseases.
The cardiovascular system is composed of the heart and the vascular system, which constitute the system for transporting blood.Cardiovascular activity can change cardiac output and peripheral resistance, coordinate blood flow distribution among organs and tissues under the mediation of nerve and body fluid, so as to meet the needs of blood flow of organs and tissues. The formation and development of heart and blood vessel, as well as the repair of injury and aging are regulated by many systems. Once these regulatory systems are confused, it will inevitably lead to metabolic disorders of heart and blood vessel cells, including the occurrence of cardiovascular diseases.
