Fabrication of uniform biodegradable microcages with predesigned shape printed from microarrays for sustained release of small hydrophilic molecules

Drug delivery vehicles have aroused increasing attention over the years due to their ability to protect and control the release of encapsulated cargo. However, several challenges significantly limit their wide applications including poor size distribution, uncontrollable size and shape, and leakage of loaded small hydrophilic cargos. This work introduces a novel and scalable microarray-based printing technique for preparing uniform biodegradable "microcages" with predesigned shapes for encapsulating and controlling the release of small hydrophilic molecules. The drugs encapsulated in the microcage are centrally located within solid microparticles without being exposed to the surface or dispersed throughout the polymer matrix. Here, 5(6)-carboxyfluorescein (CF) as a small and hydrophilic model drug are successfully loaded into polylactide acid (PLA) microcages with the dry loading method. Additionally, blending polycaprolactone (PCL) with PLA increases the permeability of the microcage polymer shells for controlled release. A higher PCL content results in a faster release rate of the encapsulated drug. Approximately 28 pg of CF particles can be encapsulated within individual microcages. This microcage printing technique provides a novel, scalable method for producing uniform biodegradable microcages, extending microprinting beyond microfilms and microparticles. A unique dry loading approach, independent of drug solubility, further broadens its utility for diverse biomedical applications.