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    Natural sporopollenin microcarriers: Morphological insights into their functional performance for drug encapsulation and release
    (Elsevier B.V., 2025) Aylanc, Volkan; Peixoto, Andreia F.; Akyüz, Lalehan; Vale, Nuno; Freire, Cristina; Freire, Cristina; Vilas-Boas, Miguel
    Natural sporopollenin microcapsules (SMCs) derived from pollen offer versatility and efficiency for different applications, from environmental remediation to food and therapeutics delivery. A critical gap remains in understanding the relationship between SMCs morphologies and their effectiveness in drug loading and delivery. Herein, we encapsulated 5-Fluorouracil (5-FU), a model anticancer drug, into SMCs derived from seven bee monofloral pollens, each exhibiting distinct morphological features, and examined how their loading and release performance correlated with their morphology. Microscopic and particle size analyses revealed that the chemically purified SMCs were hollow, with sizes ranging from 11.0 to 35.6 μm, without significant size changes after drug loading. Encapsulation efficiency achieved through vacuum-assisted loading (18–28 %) generally surpassed that of passive and compression loading techniques. Moreover, there was a trend of increasing encapsulation efficiency with larger SMC sizes, albeit with some exceptions. In a sequential release environment simulating the in vitro gastrointestinal tract and colonic fermentation, smaller SMCs exhibited a faster release profile, whereas larger ones demonstrated a slower sustained release. The quantity and shape of apertures on SMCs walls significantly impacted their drug-loading capacity and release characteristics. Additionally, natural SMCs remained structurally intact even in the presence of digestive enzymes, varying pH levels, and colonic bacteria, indicating minimal degradation under these conditions. Overall, the findings highlight the significant influence of SMCs morphologies on their functional performance and provide a list of SMCs-based microstructures to guide drug release applications.