Alqahtani Arwa Sultan, Pishnamazi Mahboubeh
Department of Chemistry, College of Science, Imam Mohammad ibn Saud Islamic University(IMSIU), P.O. Box, 90950, Riyadh 11623, Saudi Arabia.
Institute of Research and Development, Duy Tan University, Da Nang , Vietnam; School of Medicine and Pharmacy, Duy Tan University, Da Nang, Vietnam.
Eur J Pharm Sci. 2025 Nov 1;214:107253. doi: 10.1016/j.ejps.2025.107253. Epub 2025 Sep 2.
The development of efficient drug delivery systems for hydrophobic anticancer drugs like Olaparib (OLA) remains a critical challenge in cancer therapy. This study presents a comprehensive investigation of OLA-loaded zinc oxide nanoparticles (OLA@ZnO) through integrated experimental and computational approaches to optimize pH-responsive drug delivery. ZnO nanoparticles were synthesized via a sol-gel method and characterized using SEM, XRD, FTIR, and UV-Vis spectroscopy, revealing successful OLA loading through Zn²⁺-carbonyl coordination and π-stacking interactions. The nanocomposites exhibited excellent colloidal stability (zeta potential = 11 mV at pH 7.4) and pH-triggered drug release, with 100 % release in 20 h (physiological pH) versus 90 % in 24 h (acidic pH). Korsmeyer-Peppas modeling confirmed diffusion-dominated release (n = 0.52) at neutral pH and erosion-controlled release (n = 0.69) in acidic conditions. Density functional theory (DFT) calculations revealed strong charge transfer, evidenced by a narrowed HOMO-LUMO gap (4.89 → 3.21 eV) and increased dipole moment (5.7 → 9.13 D). Molecular descriptors highlighted enhanced reactivity (softness = 0.621 eV⁻¹) and pH sensitivity (electrophilicity = 4.54 eV), while reduced density gradient (RDG) analysis visualized key binding interactions (-0.9 eV for Zn²⁺-C = O coordination). Thermodynamic analysis demonstrated spontaneous adsorption (ΔG = -0.77 to -0.89 eV) with exothermic behavior (ΔH = -0.87 to -1.00 eV) and entropy-driven release (ΔS = -0.00034 to -0.00037 eV/K). Size-dependent trends showed that smaller nanoparticles (0.9 nm) enabled rapid release (τ = 1.05 s) for acute therapy, while larger nanoparticles (2.0 nm) provided sustained delivery (τ = 152 s) for chronic treatment. These findings establish a robust structure-property relationship for designing tunable ZnO-based nanocarriers, offering a promising strategy to improve the therapeutic efficacy of OLA and other hydrophobic drugs in targeted cancer therapy.
为奥拉帕尼（OLA）等疏水性抗癌药物开发高效的药物递送系统仍然是癌症治疗中的一项关键挑战。本研究通过综合实验和计算方法，对负载OLA的氧化锌纳米颗粒（OLA@ZnO）进行了全面研究，以优化pH响应性药物递送。通过溶胶-凝胶法合成了ZnO纳米颗粒，并使用扫描电子显微镜（SEM）、X射线衍射（XRD）、傅里叶变换红外光谱（FTIR）和紫外-可见光谱进行了表征，结果表明通过Zn²⁺-羰基配位和π-堆积相互作用成功负载了OLA。纳米复合材料表现出优异的胶体稳定性（在pH 7.4时zeta电位 = 11 mV）和pH触发的药物释放，在20小时（生理pH）内释放100%，而在24小时（酸性pH）内释放90%。Korsmeyer-Peppas模型证实了在中性pH下以扩散为主的释放（n = 0.52）以及在酸性条件下以侵蚀控制的释放（n = 0.69）。密度泛函理论（DFT）计算显示出强烈的电荷转移，这通过HOMO-LUMO能隙变窄（4.89 → 3.21 eV）和偶极矩增加（5.7 → 9.13 D）得以证明。分子描述符突出了增强的反应性（软度 = 0.621 eV⁻¹）和pH敏感性（亲电性 = 4.54 eV），而密度降低梯度（RDG）分析可视化了关键的结合相互作用（Zn²⁺-C = O配位为-0.9 eV）。热力学分析表明自发吸附（ΔG = -0.77至-0.89 eV）具有放热行为（ΔH = -0.87至-1.00 eV）和熵驱动的释放（ΔS = -0.00034至-0.00037 eV/K）。尺寸依赖性趋势表明，较小的纳米颗粒（0.9 nm）能够实现急性治疗的快速释放（τ = 1.05 s），而较大的纳米颗粒（2.0 nm）则为慢性治疗提供持续递送（τ = 152 s）。这些发现为设计可调节的基于ZnO的纳米载体建立了强大的结构-性质关系，为提高OLA和其他疏水性药物在靶向癌症治疗中的疗效提供了一种有前景的策略。
