Fucoidan-Coated Liposomes: A Target System to Deliver the Antimicrobial Drug Usnic Acid to Macrophages Infected with Mycobacterium tuberculosis

Abstract

The present study describes the use of fucoidan, a negative sulfated polysaccharide, as a coating material for the development of liposomes targeted to macrophages infected with Mycobacterium tuberculosis. First, fucoidan was chemically modified to obtain a hydrophobized-fucoidan derivative (cholesteryl-fucoidan) using a two-step microwave-assisted (μW) method. The total reaction time was decreased from 14 hours to 1 hour while maintaining the overall yield. Cholesterylfucoidan was then used to prepare surface-modified liposomes containing usnic acid (UA-LipoFuc), an antimicrobial lichen derivative. UA-LipoFuc was evaluated for mean particle size, polydispersity index (PDI), surface charge (ζ), and UA encapsulation efficiency. In addition, a cytotoxicity study, competition assay and an evaluation of antimycobacterial activity against macrophages infected with M. tuberculosis (H37Ra) were performed. When the amount of fucoidan was increased (from 5 to 20 mg), vesicle size increased (from 168 ± 2.82 nm to 1.18 ± 0.01 μm). Changes in from +20 ± 0.41 mV for uncoated liposomes to −5.41 ± 0.23 mV for UA-LipoFuc suggested that the fucoidan was placed on the surface of the liposomes. UA-LipoFuc exhibited a lower IC50 (8.26 ± 1.11 μM) than uncoated liposomes (18.37 ± 3.34 μM), probably due to its higher uptake. UA-LipoFuc5 was internalized through the C-type carbohydrate recognition domain of the cell membrane. Finally, usnic acid, both in its free form and encapsulated in fucoidan-coated liposomes (UA-LipoFuc5), was effective against infected macrophages. Hence, this preliminary investigation suggests that encapsulated usnic acid will aid in further studies related to infected macrophages and may be a potential option for tuberculosis treatment.

Fucoidan in Pharmaceutical Formulations: A Comprehensive Review for Smart Drug Delivery Systems

“…Salviano et al synthesized a fucoidan derivative (cholesteryl–fucoidan) loaded with usnic acid as a liposomal drug delivery system for the treatment of Mycobacterium tuberculosis infection. Fucoidan-coated liposomes showed significantly lower IC 50 (8.26 ± 1.11 μM) compared to blank liposomes due to the higher cellular uptake and cellular internalization of the hydrophobic fucoidan derivative liposomal formulation [ 94 ].…”

Novel Fucoidan Pharmaceutical Formulations and Their Potential Application in Oncology—A Review

“…Salviano et al developed a liposomal drug delivery system composed of fucoidan derivative (cholesteryl-fucoidan) loaded with usnic acid for the treatment of Mycobacterium tuberculosis infection. The formulated systems showed significantly lower IC50 (8.26 ± 1.11 µM) compared to blank liposomes, due to higher uptake and cellular internalization [174]. In another study, Zhang et al formulated liposomes as delivery systems for bioactive nutraceuticals by coating them with fucoidan.…”

Emerging strategies in nanotechnology to treat respiratory tract infections: realizing current trends for future clinical perspectives

“…The liposomal vesicle size was 168 nm −1.18 µm in diameter and −5.41 mV zeta potential. The in-vitro cytotoxicity analysis revealed higher cellular uptake and lower IC 50 values against infected macrophages as compared to uncoated liposomes (Lima Salviano et al., 2021 ). A. baumannii is a severe pathogen with a higher mortality rate and has clinical challenges due to limited therapeutic options.…”