Nanoencapsulation of Mycolic acids as a deliverable to macrophages

Abstract

The cell wall envelope of Mycobacterium tuberculosis contains unique high molecular weight lipids. Of these, the most abundant are mycolic acids, an extended family of long 2-alkyl 3-hydroxyl fatty acids, typically 70-90 carbon atoms in length, with peculiar physical and biological properties. For example, in a mouse model of asthma it was shown that mycolic acids can suppress inhaled allergen triggered inflammation, demonstrating their potential as immunotherapeutic agents. Due to the extremely hydrophobic nature of mycolic acids, a suitable vehicle is needed to introduce them into the body and guide them to their natural macrophage targets. The objective of this project was to explore the encapsulation of mycolic acids into delivery vehicles in order to assess the feasibility of an alternative means of delivery and addressing the challenge of low solubility. As vehicles nanoparticles have the advantage over liposomes in that they can increase the stability of the drug as well as effect controlled release of the agent by in vivo particle degradation. The authors demonstrate how mycolic acids rapidly exchange among liposomes, even at low temperatures, which can be extrapolated to suggest their rapid distribution in the body after administration. As an alternative, mycolic acids were encapsulated in PLGA nanoparticles of an average size of 500 nm for administration. Particles were characterized and subjected to in vitro analyses in order to determine their uptake and localization in macrophage cell lines and CaCo-2 cells. This was performed via confocal microscopy. The authors were able to demonstrate that mycolic acids can be taken up by macrophages irrespective of the liposomal or nanoparticulate vehicle that is used for their mobilization, but that the pharmacodynamics of distribution in the body will be different, depending on the vehicle.