The production and design of innovative in-body microcarrier platforms for the controlled delivery of bioactive substances to predefined sites continue to hold substantial promise for biotechnology and medicine by increasing their therapeutic benefits. In this scope, plant pollen-based biocapsules, sporopollenin structures, have emerged as an alternative to synthetic ones due to their low-cost, highly uniform size distribution, resistance to physical and chemical conditions, and renewable green sources. Sporopollenin-based microcarriers, acting as a cargo and protective system, can be engineered to tune the biodistribution and therapeutic efficacy of encapsulated pharmaceuticals. Despite these benefits, the attained biocapsules directly from the plant, which have been the subject of research for nearly two decades, face several challenges and limitations, such as their availability without disrupting their layer integrity for all pollen species, dosage tuning, and the exact control of their responses on the immune system. Recent reports of successful oral administration seem, nevertheless, to bring them one step closer to clinical applications. Herein, we discuss the challenges, possible solutions for broadening natural resources and access to pollen, their further development towards the improvement of controlled release and prolonging the residence time in the intestinal lumen, and promising applications in the in vivo models and clinical trials, focusing on progress in biocapsule technology and the main events occurring along the way.
