Kalyanram Poornima, Puri Anu, Gupta Anju
Department of Mechanical, Industrial and Manufacturing Engineering, University of Toledo, Toledo, OH 43606 USA.
RNA Biology Laboratory, National Cancer Institute At Frederick, Frederick, MD 21702 USA.
J Therm Anal Calorim. 2022;147(11):6337-6348. doi: 10.1007/s10973-021-10929-6. Epub 2021 Jun 26.
In this work, we demonstrate the enhanced thermal and steric stability of lipid-based formulations in the presence of encapsulated HPPH that have demonstrated potential cancer applications in previously presented in vivo studies. Differential scanning calorimeter (DSC) was used to study the phase transitions, and domain formations, and to qualify the thermodynamic properties associated with change in lipid bilayer behavior due to the presence of PEGylated at varying concentrations and sizes, and the encapsulated HPPH molecules. Thermal instability was quantified by dramatic changes in calculated enthalpy, and the shape of the melting peak or calculated half width of melting peak. This systematic study focused on understanding the effects of varying molecular mass and concentrations of PEG polymers in the photopolymerizable lipid DCPC lipid bilayer matrix for four weeks at room temperature of 25 °C. The major findings include increased thermal stability of the lipid bilayer due to the presence of PEG-2 K and the HPPH that resulted from the van der Waals forces between various molecular species, and the change in bilayer curvature confirmed via mathematical correlations. It is demonstrated that the encapsulation of therapeutics in lipid formulations can alter their overall thermal behavior, and therefore, it is imperative to consider calorimetric effects while designing lipid-based vaccines. The presented research methodologies and findings presented can predict the stability of lipid-based vaccines that are under development such as COVID-19 during their storage, transport, and distribution.
在这项工作中，我们证明了在存在封装的HPPH的情况下，脂质基制剂具有更高的热稳定性和空间稳定性，HPPH在先前的体内研究中已显示出潜在的癌症应用。差示扫描量热仪（DSC）用于研究相变、结构域形成，并确定与由于不同浓度和尺寸的聚乙二醇化以及封装的HPPH分子的存在而导致的脂质双层行为变化相关的热力学性质。通过计算焓的显著变化、熔融峰的形状或计算的熔融峰半高宽来量化热不稳定性。这项系统研究的重点是了解在25°C室温下，可光聚合脂质DCPC脂质双层基质中不同分子量和浓度的聚乙二醇聚合物在四周内的影响。主要发现包括由于PEG-2K和HPPH的存在导致脂质双层的热稳定性增加，这是由各种分子物种之间范德华力引起的，并且通过数学相关性证实了双层曲率的变化。结果表明，将治疗剂封装在脂质制剂中可以改变其整体热行为，因此，在设计基于脂质的疫苗时必须考虑量热效应。所提出的研究方法和发现可以预测正在开发的基于脂质的疫苗（如COVID-19疫苗）在储存、运输和分发过程中的稳定性。
