The natural biological macromolecule sporopollenin capsules in biomedical applications: A systematic review...

Pharmaceutical materials science is shifting from synthetic nanotechnology toward naturally occurring micro-architectures. Sporopollenin Exine Capsules (SECs), derived from plant pollen, have emerged as promising candidates due to their evolutionary resilience and chemical stability. To evaluate their potential, a systematic review following PRISMA 2020 guidelines was conducted across Web of Science, Scopus, and PubMed (January 2015-July 2025). The screening process excluded agricultural and industrial applications to focus strictly on biomedical innovation, with risk of bias assessed using a modified Klimisch score for in vitro and preclinical studies. Of 2621 records, 51 original research articles met the inclusion criteria. Bibliometric analysis identified a research inflection point in 2014, marking a transition to applied materials science. Bio-sources have diversified beyond Lycopodium clavatum, with successful applications in oral drug delivery (n = 21), advanced biomedical targeting (n = 16), and material characterization (n = 14). Quantitative findings demonstrate loading efficiencies ranging from 3% to 79%, carrier sizes typically 10-75 μm, and tunable release kinetics engineered for targeted delivery. Overall, SECs demonstrate high biocompatibility, diverse loading capabilities, and functional advantages such as mucoadhesion. However, a "translational gap" remains between material characterization and clinical implementation. Future research must focus on standardized extraction protocols, comprehensive safety profiles, and clarification of regulatory pathways to enable clinical translation.