Physiological reflexes and anatomical barriers render traditional eye drop delivery inefficient. We previously reported that drug-loaded nanoparticles and microspheres prepared from montmorillonite and Eudragit polymers exhibited good sustained-release and lowered intraocular pressure. Here, we compared the performance of optimized formulations to select the most suitable formulation for glaucoma therapy. We found that the microspheres had much higher encapsulation efficiency and drug loading than nanoparticles. Moreover, cytocompatibility experiments demonstrated that nanoparticles showed more severe cytotoxicity than microspheres, probably due to their smaller particles, enhanced cell uptake, and intracellular solubility. Interestingly, the pre-corneal retention time of nanoparticles reflected a clear advantage over microspheres, while the duration of the pharmacological effect of nanoparticles was not as good as that of microspheres: compared with the nanoparticle depressurization duration of only 8 h, the microspheres continuously depressurized for 12 h. The slower release of the microspheres and its micro-interaction mechanism with the discontinuous mucin layer of the tear film led to the inconsistency between duration of pharmacodynamics and fluorescence ocular retention time. In summary, the lower cytotoxicity and longer pharmacological effect of microspheres indicate their potential advantages for glaucoma applications.

生理反射和解剖学障碍使传统的眼药水递送效率低下。我们以前曾报道过，由蒙脱土和Eudragit聚合物制备的载有药物的纳米颗粒和微球表现出良好的持续释放和降低的眼内压。在这里，我们比较了优化配方的性能，以选择最适合青光眼治疗的配方。我们发现微球比纳米颗粒具有更高的封装效率和载药量。此外，细胞相容性实验表明，与微球相比，纳米颗粒显示出更严重的细胞毒性，这可能是由于其较小的颗粒，增强的细胞摄取和细胞内溶解度。有趣的是，纳米粒子在角膜前的保留时间比微球体现出明显的优势，纳米颗粒的药理作用持续时间不如微球体持续：与仅8 h的纳米颗粒降压持续时间相比，微球体持续降压12 h。微球的缓慢释放及其与泪膜不连续粘蛋白层的微相互作用机制导致药效学持续时间与荧光眼保留时间之间的不一致。总之，微球的较低的细胞毒性和较长的药理作用表明它们在青光眼应用中的潜在优势。微球的缓慢释放及其与泪膜不连续粘蛋白层的微相互作用机制导致药效学持续时间和荧光眼保留时间之间的不一致。总之，微球的较低的细胞毒性和较长的药理作用表明它们在青光眼应用中的潜在优势。微球的缓慢释放及其与泪膜不连续粘蛋白层的微相互作用机制导致药效学持续时间和荧光眼保留时间之间的不一致。总之，微球的较低的细胞毒性和较长的药理作用表明它们在青光眼应用中的潜在优势。