Micro-interaction of mucin tear film interface with particles: The inconsistency of pharmacodynamics and precorneal retention of ion-exchange, functionalized, Mt-embedded nano- and microparticles.

• Montmorillonite was used in combine with Eudragit to prepare nano-micro particles. • Both nano- and microparticles improve the pre-corneal retention capacity of drug. • The pre-corneal retention capacity and pharmacodynamics were inconsistent. • Microspheres show better biocompatibility compared with nanoparticles. 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. [ABSTRACT FROM AUTHOR]