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Life sciences · Journal article
Admet & Dmpk · October 13, 2026
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Background and purpose: 5‑fluorouracil (5‑FU) is a widely used antimetabolite chemotherapeutic agent. However, it has substantial cytotoxicity and may cause serious adverse effects, including gastrointestinal toxicity, myelosuppression, and, less commonly, cardiac and neurologic toxicity. To achieve sustained release and reduce systemic exposure and administration frequency, 5-FU can be microencapsulated in biodegradable, non-toxic polyhydroxyalkanoate matrices. Experimental approach: In this research, 5-FU-loaded poly(3-hydroxybutyrate) (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P3HBV) micro- and nanoparticles were prepared via spray drying and single emulsion solvent evaporation methods. The obtained particles were characterized in terms of their average hydrodynamic size, zeta potential, surface morphology, drug loading, encapsulation efficiency, release patterns, hemolytic activity, and cytotoxicity to HeLa cervical cancer cells. Key results: The obtained 5-FU-loaded micro- and nanoparticles had a regular spherical shape without surface defects. The nanoparticles were nearly identical in size regardless of the presence of 5‑FU. In contrast, the encapsulation of 5‑FU into microparticles by spray drying caused measurable increases in particle size, with the average hydrodynamic diameter increasing by 21.0 % for P3HB and by 28.6 % for P3HBV. Although the single emulsion solvent evaporation technique did not achieve therapeutically relevant 5‑FU loading, spray-dried microparticles showed satisfactory drug loading and sustained release of 5-FU over 48 h. The microparticles exhibited pronounced cytotoxicity against HeLa cervical cancer cells while demonstrating lower hemolytic activity than free 5‑FU. Conclusion: In this study, the promising drug-loaded systems based on polyhydroxyalkanoate microparticles were prepared and characterized for sustained 5-FU delivery in the therapy of cervical cancer.