DICMaPI, Università degli Studi di Napoli Federico II, P. le Tecchio 80, 80125 Napoli, Italy.
Laboratory for Neutron Scattering & Imaging, Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland.
Langmuir. 2024 Jan 16;40(2):1544-1554. doi: 10.1021/acs.langmuir.3c03682. Epub 2024 Jan 3.
Age-long ambition of medical scientists has always been advancement in healthcare and therapeutic medicine. Biomedical research indeed claims paramount importance in nanomedicine and drug delivery, and the development of biocompatible storage structures for delivering drugs stands at the heart of emerging scientific works. The delivery of drugs into the human body is nevertheless a nontrivial and challenging task, and it is often addressed by using amphiphilic compounds as nanosized delivery vehicles. Pluronics belong to a peculiar class of biocompatible and thermosensitive nonionic amphiphilic copolymers, and their self-assemblies are employed as drug delivery excipients because of their unique properties. We herein report on the encapsulation of diclofenac sodium within Pluronic F68 self-assemblies in water, underpinning the impact of the drug on the rheological and microstructural evolution of pluronic-based systems. The self-assembly and thermoresponsive micellization were studied through isothermal steady rheological experiments at different temperatures on samples containing 45 wt % Pluronic F68 and different amounts of diclofenac sodium. The adoption of scattering techniques, small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), allowed for the description of the system features at the nanometer length scale, providing information about the characteristic size of each part of the micellar structures as a function of temperature and drug concentration. Diclofenac sodium is not a good fellow for Pluronic F68. The triblock copolymer aids the encapsulation of the drug, highly improving its water solubility, whereas diclofenac sodium somehow hinders Pluronic self-assembly. By using a simple empirical model and no fitting parameters, the steady viscosity can be predicted, although qualitatively, through the volume fraction of the micelles extracted through scattering techniques and compared to the rheological one. A tunable control of the viscous behavior of such biomedical systems may be achieved through the suitable choice of their composition.
医学科学家们一直以来的雄心壮志就是在医疗保健和治疗医学方面取得进步。生物医学研究在纳米医学和药物输送方面确实具有至关重要的意义，而开发用于输送药物的生物相容性储存结构是新兴科学工作的核心。然而，将药物递送到人体内是一项非常复杂和具有挑战性的任务，通常使用两亲性化合物作为纳米级药物输送载体来解决。泊洛沙姆属于一类特殊的生物相容性和温度敏感的非离子两亲性嵌段共聚物，其自组装被用作药物输送赋形剂，因为它们具有独特的性质。我们在此报告了将双氯芬酸钠包封在 Pluronic F68 自组装体中，研究了药物对基于 Pluronic 的系统流变学和微观结构演变的影响。通过在不同温度下对含有 45wt% Pluronic F68 和不同量双氯芬酸钠的样品进行等温稳态流变实验，研究了自组装和温度响应性胶束化。采用散射技术，小角 X 射线散射（SAXS）和小角中子散射（SANS），可以描述纳米尺度上的系统特征，提供关于胶束结构各部分特征尺寸随温度和药物浓度变化的信息。双氯芬酸钠与 Pluronic F68 不太和谐。三嵌段共聚物有助于药物的包封，极大地提高了其水溶性，而双氯芬酸钠在某种程度上阻碍了 Pluronic 的自组装。通过使用简单的经验模型和无拟合参数，可以预测稳态粘度，尽管是定性的，通过从散射技术中提取的胶束的体积分数，并与流变学进行比较。通过适当选择其组成，可以实现对这些生物医学系统粘性行为的可调控制。
