ScholarWorks@동국대학교

초록

Although lipid nanoparticles (LNP) are potential carriers of various pharmaceutical ingredients, further inves-tigation for maintaining their stability under various environmental stressors must be performed. This study evaluated the influence of PEGylation and stress conditions on the stability of siRNA-loaded LNPs with different concentrations of PEG (0.5 mol%; 0.5 % PEG-LNP and 1.0 mol%; 1.0 % PEG-LNP) anchored to their surface. We applied end-over-end agitation, elevated temperature, and repeated freeze and thaw (F/T) cycles as physico-chemical stressors of pH and ionic strength. Dynamic light scattering (DLS), flow imaging microscopy (FIM), and ionic-exchange chromatography (IEX) were to determine the degree of aggregation and change in siRNA content. The results indicate that 0.5 % PEG-LNP resisted aggregation only at low pH levels or with salt, whereas 1.0 % PEG-LNP had increased colloidal stability except at pH 4. 0.5 % PEG-LNP withstood aggregation until 71 degrees C and three cycles of F/T. In contrast, 1.0 % PEG-LNP maintained colloidal stability at 90 degrees C and seven F/T cycles. Moreover, 1.0 % PEG-LNP had higher siRNA stability under all stress conditions. Therefore, to ensure the sta-bility of LNP and encapsulated siRNA, the PEG concentration must be carefully controlled while considering LNPs' colloidal instability mechanisms under various stress conditions.

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