Preparation of Terpenoid-Invasomes with Selective Activity against S. aureus and Characterization by Cryo Transmission Electron Microscopy

Abstract

Terpenoids are natural plant-derived products that are applied to treat a broad range of human diseases, such as airway infections and inflammation. However, pharmaceutical applications of terpenoids against bacterial infection remain challenging due to their poor water solubility. Here, we produce invasomes encapsulating thymol, menthol, camphor and 1,8-cineol, characterize them via cryo transmission electron microscopy and assess their bactericidal properties. While control- and cineol-invasomes are similarly distributed between unilamellar and bilamellar vesicles, a shift towards unilamellar invasomes is observable after encapsulation of thymol, menthol or camphor. Thymol- and camphor-invasomes show a size reduction, whereas menthol-invasomes are enlarged and cineol-invasomes remain unchanged compared to control. While thymol-invasomes lead to the strongest growth inhibition of S. aureus, camphor- or cineol-invasomes mediate cell death and S. aureus growth is not affected by menthol-invasomes. Flow cytometric analysis validate that invasomes comprising thymol are highly bactericidal to S. aureus. Notably, treatment with thymol-invasomes does not affect survival of Gram-negative E. coli. In summary, we successfully produce terpenoid-invasomes and demonstrate that particularly thymol-invasomes show a strong selective activity against Gram-positive bacteria. Our findings provide a promising approach to increase the bioavailability of terpenoid-based drugs and may be directly applicable for treating severe bacterial infections such as methicillin-resistant S. aureus.

Towards Advances in Medicinal Plant Antimicrobial Activity: A Review Study on Challenges and Future Perspectives

“…They also showed varying degrees of antimicrobial activity against various pathogenic fungi [ 156 , 158 , 159 , 160 , 161 ]. Although antibacterial activity of terpenes remains challenging due to their poor solubility, terpenes show a strong activity especially against Gram-positive bacteria [ 123 , 162 , 163 ]. Several terpenoid derivatives, such as diterpenoids, also exhibit antimicrobial activity against bacterial fungi, viruses and protozoa with the emphasis on Mycobacterium tuberculosis [ 164 ].…”

Vesicular Nanocarriers for Phytocompounds in Wound Care: Preparation and Characterization

“…In this sense, terpenoids have strong antioxidant and anti-inflammatory as well as antimicrobial properties. However, the pharmaceutical applications of terpenoids remain challenging due to their poor water solubility and high volatility [ 28 ]. The aqueous extract of Moringa oleifera [ 29 ] was also found to reduce the levels of inflammatory markers in macrophages, including induced nitric oxide synthase (iNOS), TNF-α, and IL-1β [ 29 ].…”

“…Invasomes are liposomes composed of unsaturated phospholipids, such as phosphatidylcholine, small amounts of ethanol, one or more different terpenes, and water. In addition to biological activity due to the antimicrobial, anti-inflammatory, and strong antioxidant properties, terpenoids can also serve as permeation enhancers for transdermal delivery and bioavailability enhancers [ 28 ]. Recent research shows that terpenes may enhance skin permeation through disruption of the stratum corneum lipids, interacting with intracellular proteins, and improving the distribution of the drug into the stratum corneum.…”

Topical Administration of Terpenes Encapsulated in Nanostructured Lipid-Based Systems

“…Anti-inflammatory, bacterial infections e.g., MRSA [52] An equally important therapeutic aspect of terpenes is their activity against skin cancer. The number of skin cancer cases has increased rapidly worldwide.…”