Nano-Rifabutin entrapment within glucan microparticles enhances protection against intracellular Mycobacterium tuberculosis

Abstract

Recently, yeast-derived glucan particles (GP) have emerged as novel drug delivery agents that provide for receptor-mediated uptake by phagocytic cells expressing b-glucan receptors. In our previous study, we prepared GP loaded with high payload (40.5 þ 1.9%) of rifabutin (RB) nano-particles [(RB-NPs)-GP]. We investigated the anti-mycobacterial efficacy and cellular activation responses within Mycobacterium tuberculosis (M. tuberculosis) infected J774 macrophage cells following exposure to the (RB-NPs)-GP formulation. The exposure was seen to augment a robust innate immune response including the induction of reactive oxygen and nitrogen species, autophagy and apoptosis within M. tuberculosis infected macrophage. Further, the efficacy testing of these particles in murine macrophage exhibited that the (RB-NPs)-GP formulation enhanced the efficacy of RB drug by $2.5 fold. The study suggests that the set of innate responses conducive to killing intracellular bacteria evoked by (RB-NPs)-GP play a pivotal role in impeding the intracellular M. tuberculosis survival, resulting in enhanced efficacy of the formulation. Our results establish that the (RB-NPs)-GP formulation not only activate M. tuberculosis infected, immune-suppressed macrophage, but also adds significantly to the efficacy of loaded drug, and thus forms a promising approach that should be explored further as an alternative or adjunct form of TB therapy. HIGHLIGHTS Nano-Rifabutin loaded Glucan microparticles [(RB-NPs)-GP] administered to M. tuberculosis infected macrophage. (RB-NPs)-GP induces appropriate innate immune responses in host macrophage. Mycobactericidal Effect of Rifabutin was markedly enhanced by its nano-entrapment in GP. Intracellular drug delivery supplements the innate response in M. tuberculosis infected macrophage.

Binding and Release of FeIII Complexes from Glucan Particles for the Delivery of T1 MRI Contrast Agents

“…The unusual properties of cationic Fe(III) T1 MRI contrast agents studied here facilitate labelling of GPs without further functionalization of the complexes or incorporation into liposomes as necessary for most dyes or contrast agents. 4,5,9 We propose that the cationic nature of the complexes enables this tight encapsulation in GPs, which are known to be negatively charged. 2,5,9 Further, Fe(TOB) shows higher loading than the Fe(TOT) complex suggesting additional coordination interactions with the GPs.…”

“…4,5,9 We propose that the cationic nature of the complexes enables this tight encapsulation in GPs, which are known to be negatively charged. 2,5,9 Further, Fe(TOB) shows higher loading than the Fe(TOT) complex suggesting additional coordination interactions with the GPs. The Fe(III) complex must be released from the GPs, however, to produce enhanced T1 water proton relaxivity.…”

“…To circumvent the high porosity of the particles, the small molecules may be encapsulated into nanoparticles or liposomes first, and then loaded inside the GP. 5,9,10 Release of the liposome encapsulated dye is facilitated by heating the GPs. 7 Another method to promote successful entrapment is to add long hydrophobic alkyl chains on the dye or on the MRI contrast agent.…”

Nanobiosystems for Antimicrobial Drug-Resistant Infections

“…Recent cases of non-lipidic NPs studied in vitro against MTB include graphene oxide (GO) nanocarriers co-loaded with Rifampicin and Isoniazid and coated with chitosan and Gum Tragacanth [ 208 ]; Rifampicin and curcumin co-loaded polymeric NPs that showed high efficacy against MTB infected macrophages [ 209 ]; Rifabutin-loaded glucan microparticles that demonstrated enhanced protection against intracellular M. tuberculosis [ 210 ], and Moxifloxacin poly(butyl cyanoacrylate (PBCA) NPs that improved the drug effect against M. tuberculosis in macrophages [ 211 ].…”

Chemical remediation of Aflatoxin B1 using encapsulated polyvinylpyrrolidone as an environmental-friendly control.

“…A preparation of chemically modified Saccharomyces cerevisiae cell wall has been shown to adsorb selected major mycotoxins in vitro [15][16][17] and alleviate the effect of dietary mycotoxin exposure in various animal species [18][19][20]. Yeast cell wall are composed mainly of polysaccharides, proteins, and lipids which offer numerous functional groups for the interaction, such as carboxyl, hydroxyl, phosphate and amine groups, as well as hydrophobic adsorption sites, such as aliphatic chains and aromatic carbon rings [21,22].…”