Fucoidan coated liposomes loaded with novel antituberculosis agent: preparation, evaluation, and cytotoxicity study

Abstract

In this article, we described a novel antituberculosis imidazotetrazine derivative designed in fucoidan-coated liposomes to reduce its cytotoxicity and investigate its mucoadhesive properties. Firstly, fucoidan extracted from Ascophyllum nodosum was used for additional stabilization of liposomal suspensions and to give it mucoadhesive properties. PEG-600 and/or Tween-80 were used to increase the shelf life of liposomal suspension. The ratio of the fucoidan: lipids 1:2 was found to be the optimum that produces stable fucoidan-coated liposomes. The particle size of the optimum formulation was 336.3 ± 5.4, the PDI was 0.33, and the zeta potential was −39.6. This size and the practical spherical shape of the particles were confirmed by atomic force microscopy. In addition, the in vitro release profiles from uncoated and fucoidan-coated liposomes revealed significant and faster release compared to free antituberculosis agent. Using the MTT assay test, the fucoidan-coated liposomes exhibited fourteen times lower cytotoxicity (IC₅₀ 7.14 ± 0.91 µg/ml) than the free drug (IC₅₀ 0.49 ± 0.06). Moreover, the mucoadhesive capabilities of these liposomal formulations were also confirmed using snail mucin, which highlighting their potential use as an effective delivery system for antituberculosis therapy, with notable improvements in dissolution rate and reduced cytotoxicity.

Keywords:

• Fucoidan
• tuberculosis
• lipososmes
• zeta potential
• cytotoxicity

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Emanuela T. Bulya and Maxim A. Mironov thank the Russian Science Foundation for financial support Grant 20-66-47017. The equipment of the Ural Center for Shared Use «Modern nanotechnology» Ural Federal University (Reg.№ 2968), which is supported by the Ministry of Science and Higher Education RF (Project № 075-15-2021-677), was used for AFM investigation. The study of cytotoxic effect was financially supported by the Ministry of Science and Higher Education of the Russian Federation within the framework of the Program of the Development of the Ural Federal University named after the first President of Russia B. N. Yeltsin under the Federal Academic Leadership Programme ‘Priority 2030. Manar M. Obiedallah would like to acknowledge the partial financial support provided by the Egyptian Ministry of Higher Education and Scientific Research.