Encapsulation and controlled release of halogenated natural products in nanoformulations for enhanced stability and biological activity

Abstract

Marine seaweeds, or macroalgae, represent a prolific source of natural products with promising antibacterial and antifungal properties. These organisms produce a wide array of secondary metabolites, including halogenated compounds, which exhibit potent activity against drug-resistant bacterial and fungal strains. The therapeutic development of these compounds is hindered by challenges related to their lipophilicity, poor solubility and limited stability under physiological conditions. However, such challenges can be addressed through advanced formulation strategies such as nanoencapsulation. Therefore, this study aims to address these limitations by developing solid lipid nanoparticle (SLNs) based formulations for halogenated compounds to enhance their solubility, stability and biological efficacy. Two identified monoterpenes (1 and 2) were isolated and characterized using standard chromatographic and spectroscopic techniques. Structural assignment was established using standard TOCSY, 1D and 2D NMR experiments. SLNs formulations were prepared by hot homogenization followed by ultra sound technique, and evaluated using dynamic light scattering for their sizes and zeta potential. SEM images confirmed that the fabricated SLNs were spherical in shape. FTIR showed that there were no interactions between compounds and the lipid. Antimicrobial activity against clinically relevant bacterial and fungal pathogens was evaluated using a resazurin-based micro dilution assay, with the results expressed as the percentage (%) of resazurin reduction relative to the untreated control. Screening revealed that the compounds had weak antimicrobial activity, whereas, SLNs formulations had improved antimicrobial activity, reduced % resazurin reduction, against two bacterial strains, gram negative Escherichia coli and gram positive methicillin-resistant Staphylococcus aureus (MRSA), and fungal strain, Candida auris. Weak antifungal activity was observed against Candida albicans. Based on the results, this study proved that the nanoencapsulation improved the solubility and therapeutic effects of halogenated compounds.