Babinski Tatiane Patrícia, Padilha Lorenzett Ariane Krause, Ziebarth Jeferson, Lima Vanderlei Aparecido de, Mainardes Rubiana Mara
Laboratory of Nanostructured Formulations, Universidade Estadual do Centro-Oeste, Élio Antonio Dalla Vecchia St, 838, 85040-167 Guarapuava, PR, Brazil.
Chemistry Department, Universidade Tecnológica Federal do Paraná, 85503-390 Pato Branco, PR, Brazil.
ACS Omega. 2025 Mar 28;10(13):13440-13452. doi: 10.1021/acsomega.4c11636. eCollection 2025 Apr 8.
Zein-based nanoparticles offer significant potential as carriers for drug delivery due to their biocompatibility. However, optimizing their formulation is essential to achieving efficient encapsulation and stability. This study aimed to optimize the formulation of zein-casein-hyaluronic acid-based nanoparticles for the encapsulation of a hydrophilic drug, focusing on achieving favorable physicochemical properties for oral drug delivery applications. A factorial experimental design was employed to evaluate the influence of key formulation parameters, including zein concentration, hyaluronic acid concentration, sodium caseinate concentration, and the organic-to-aqueous phase (O/W) ratio. Particle size (PS), polydispersity index (PDI), zeta potential, and encapsulation efficiency (EE) were analyzed as response variables. Multivariate analyses, such as hierarchical cluster analysis and principal component analysis, were performed to explore the relationships between formulation parameters and nanoparticle properties. Model validity was confirmed by using ANOVA and residual analysis. Optimized nanoparticles exhibited a PS of 217 ± 5 nm, PDI of 0.077 ± 0.022, zeta potential of -24.7 ± 1.9 mV, and EE of 31% ± 4. The nanoparticles displayed a monomodal size distribution and a spherical morphology. Multivariate analyses revealed that the O/W ratio and zein concentration were the most influential factors, while sodium caseinate played a crucial stabilizing role. The desirability function yielded a high score ( = 0.9338), confirming the robustness of the optimization process. Stability studies demonstrated that refrigeration at 8 °C preserved the nanoparticles' physicochemical properties over 180 days. This study underscores the power of experimental design as a tool to refine nanoparticle formulations, paving the way for more efficient drug delivery systems and unlocking new possibilities for the oral administration of hydrophilic compounds.
基于玉米醇溶蛋白的纳米颗粒由于其生物相容性，在药物递送载体方面具有巨大潜力。然而，优化其配方对于实现高效包封和稳定性至关重要。本研究旨在优化基于玉米醇溶蛋白-酪蛋白-透明质酸的纳米颗粒配方，用于亲水性药物的包封，重点是为口服药物递送应用实现良好的物理化学性质。采用析因实验设计来评估关键配方参数的影响，包括玉米醇溶蛋白浓度、透明质酸浓度、酪蛋白酸钠浓度以及有机相-水相（O/W）比。分析粒径（PS）、多分散指数（PDI）、zeta电位和包封率（EE）作为响应变量。进行了多元分析，如层次聚类分析和主成分分析，以探索配方参数与纳米颗粒性质之间的关系。通过方差分析和残差分析确认了模型的有效性。优化后的纳米颗粒表现出217±5nm的PS、0.077±0.022的PDI、-24.7±1.9mV的zeta电位和31%±4的EE。纳米颗粒呈现单峰尺寸分布和球形形态。多元分析表明，O/W比和玉米醇溶蛋白浓度是最具影响力的因素，而酪蛋白酸钠起到了关键的稳定作用。合意性函数给出了高分（=0.9338），证实了优化过程的稳健性。稳定性研究表明，在8°C冷藏可在180天内保持纳米颗粒的物理化学性质。本研究强调了实验设计作为优化纳米颗粒配方工具的作用，为更高效的药物递送系统铺平了道路，并为亲水性化合物的口服给药开辟了新的可能性。
