Biophysical and structural characterization of biocompatible microalgae-derived vesicles as sustainable drug delivery platforms

Ivošević DeNardis, Nadica and Mišić Radić, Tea and Klacsová, Mária and Uhríková, Daniela and Frkanec, Ruža and Zemła, Joanna and Lekka, Malgorzata and Lukeš, Martin and Prášil, Ondrej and Sebőkné Nagy, Krisztina and Páli, Tibor and Lisac, Katarina and Chovancová, Marcela and Ojdanić, Karlo and Horvat, Lucija and Peharec Štefanić, Petra and Smokrović, Kristina and Maltar-Strmečki, Nadica and Pavlović Saftić, Dijana and Piantanida, Ivo and Matijević Glavan, Tanja (2026) Biophysical and structural characterization of biocompatible microalgae-derived vesicles as sustainable drug delivery platforms. ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS, 98. no.-104852. ISSN 2211-9264

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Abstract

Marine microalgae are sustainable sources of bioactive compounds and drug delivery platforms that can utilize whole cells, cell fragments, or vesicles. Although extracellular vesicles secreted by microalgae have shown potential, broader application is limited by low yields, instability, complex isolation, and poor standardization. To address these challenges, we previously proposed an alternative strategy in which hypoosmotic stress induces cell disruption, followed by self-assembly of membrane fragments into reconstructed microalgae-derived vesicles. Here, a comprehensive biophysical approach combining top-down and bottom-up strategies provides insight into vesicle structural features relevant to their function as drug delivery platforms. They form a heterogeneous population but can be reduced to the nanometer range. Their pigmented membranes contain chlorophyll degradation products and carotenoids, and provide significant antioxidant activity. The protein-to-lipid ratio of cells and vesicles is maintained mainly during self-assembly, indicating an effective reconstruction process. Vesicles have a balanced fatty acid profile, hydrophilicity, pronounced softness, and structure-dependent permeability. In vitro cytotoxicity studies indicated that vesicles do not exhibit acute cellular toxicity and show only mild, cell line-dependent effects at high concentrations. An in vivo immunogenicity study also demonstrated mild adjuvant activity. Confocal imaging shows that a glycopeptide antibiotic and an oligonucleotide bind via non-covalent interactions with the membrane surface. A lyophilization and rehydration protocol was developed to extend material stability, highlighting the importance of the self-assembly process during which vesicle morphology is preserved. These findings provide proof of concept that reconstructed microalgae-derived vesicles can be used to develop next-generation sustainable and safe drug delivery platforms.

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