Freeze-drying is an effective approach to improve the long-term stability of nanomedicines. Lyoprotectants are generally considered as requisite excipients to ensure that the quality of nanoparticles is maintained throughout the freeze-drying process. However, depending on the type of nanoparticles, the needs for lyoprotectants or the challenges they face during freeze-drying may be different. In this study, we compared and identified the impact of freeze-drying on key characteristics of three types of nanoparticles: solid lipid nanoparticles (SLNs), polymeric nanoparticles (PNs), and liposomes. Sucrose, trehalose, and mannitol were added to nanoparticle suspensions before freeze-drying. The same conservative freeze-drying conditions with controlled ice nucleation at −8 °C were employed for all formulations. The collapse temperatures of nanoparticle formulations were found to be the same as those of the lyoprotectant added, except PN formulation. Likely the poly(vinyl alcohol) (PVA) in the formulation induced a higher collapse temperature and retardation of drying of PNs. Freeze-drying of both SLNs and liposomes without lyoprotectants increased particle size and polydispersity, which was resolved by adding amorphous disaccharides. Regardless of the addition of lyoprotectants, freeze-drying did not alter the size of PNs possibly due to the protection from PVA. However, lyoprotectants were still necessary to shorten the reconstitution time and reduce the residual moisture. In conclusion, different types of nanoparticles face distinct challenges for freeze-drying, and lyoprotectants differentially affect various stability and quality attributes of freeze-dried nanoparticles.

冷冻干燥是提高纳米药物长期稳定性的有效方法。冻干保护剂通常被认为是必需的赋形剂，以确保在整个冷冻干燥过程中保持纳米颗粒的质量。然而，根据纳米颗粒的类型，冻干保护剂的需求或他们在冷冻干燥过程中面临的挑战可能会有所不同。在本研究中，我们比较并确定了冷冻干燥对三种类型纳米颗粒的关键特性的影响：固体脂质纳米颗粒 (SLN)、聚合物纳米颗粒 (PN) 和脂质体。在冷冻干燥之前，将蔗糖、海藻糖和甘露醇添加到纳米颗粒悬浮液中。所有配方均采用相同的保守冷冻干燥条件，在 -8 °C 下控制冰成核。发现纳米颗粒制剂的塌陷温度与添加的冻干保护剂相同，但 PN 制剂除外。配方中的聚乙烯醇 (PVA) 可能会导致更高的塌陷温度和 PN 干燥的延迟。在没有冻干保护剂的情况下冷冻干燥 SLN 和脂质体增加了粒径和多分散性，这通过添加无定形二糖来解决。无论添加冻干保护剂，冷冻干燥都不会改变 PN 的大小，这可能是由于对 PVA 的保护。然而，仍然需要冻干保护剂来缩短重组时间并减少残留水分。总之，不同类型的纳米颗粒在冷冻干燥方面面临着不同的挑战，