Design and delivery effect of prolonged-retention dexamethasone and tacrolimus microcrystals eye drops

The improvement of drug solubility is essential for enhancing drug absorption of eye drops, particularly for poorly soluble drugs. In this study, drug crystallization techniques were utilized to synthesize dexamethasone microcrystals (DES MCs) and tacrolimus microcrystals (TAM MCs). To further enhance the retention of the MCs, DES MCs@(PEI/HA)₃ and TAM MCs@(PEI/HA)₃ were prepared by the alternate deposition of polyethyleneimine (PEI) and hyaluronic acid (HA) on the surface of the MCs through electrostatic adsorption. The sustained release effect of TAM MCs@(PEI/HA)₃, resulting from enhanced solubility through micro-crystallization, was confirmed via solubility measurements and in vitro release studies. Similarly, DES MCs@(PEI/HA)₃ exhibited comparable sustained release properties. Subsequently, the hydrophobicity, safety, and efficacy of DES MCs@(PEI/HA)₃ and TAM MCs@(PEI/HA)₃ were investigated through the in vitro and in vivo experiments. Notably, TAM MCs@(PEI/HA)₃ demonstrated superior efficacy over commercially available TALYMUS®, enabling a once-daily dosing regimen. In conclusion, microcrystal preparation exhibited a more significant impact on the delivery of tacrolimus compared to dexamethasone. The TAM MCs@(PEI/HA)₃ microcrystals suspension eye drops prepared using the layer-by-layer self-assembly technique, offer a promising strategy for enhancing the solubility of poorly soluble drugs and ocular drug delivery.