Physicochemical and Biological Evaluation of Curdlan-Poly(Lactic-Co-Glycolic Acid) Nanoparticles as a Host-Directed Therapy Against Mycobacterium Tuberculosis

Abstract

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Insights into innovative therapeutics for drug-resistant tuberculosis: Host-directed therapy and autophagy inducing modified nanoparticles

“…The study also revealed that curdlan has a high affinity for Dectin-1 receptors ( D'Souza et al, 2022 ), giving an advantage in delivering anti-TB therapeutics and AICs directly to macrophages, enhancing drug payload on targeted cells while decreasing immunotoxicity. Furthermore, the study demonstrated that the produced nanosystem was non-toxic, necessitating future research as a host-directed treatment therapy for Mtb intracellular elimination ( D'Souza et al, 2022 ).

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“…6 ) , compared to controls; compared to the RIF solution, Glu-CS-PLGA NPs delivered 4-fold more RIF into ALM ( Dube et al, 2014 ). Recent similar work by D’Souza et al found that curdlan functionalized PLGA NPs intended for host-directed therapy increased and accelerated the release of pro-inflammatory cytokine TNF-α in macrophages, resulting in lower intracellular Mtb levels within the macrophages ( D'Souza et al, 2022 ). The study also revealed that curdlan has a high affinity for Dectin-1 receptors ( D'Souza et al, 2022 ), giving an advantage in delivering anti-TB therapeutics and AICs directly to macrophages, enhancing drug payload on targeted cells while decreasing immunotoxicity.…”

“…Recent similar work by D’Souza et al found that curdlan functionalized PLGA NPs intended for host-directed therapy increased and accelerated the release of pro-inflammatory cytokine TNF-α in macrophages, resulting in lower intracellular Mtb levels within the macrophages ( D'Souza et al, 2022 ). The study also revealed that curdlan has a high affinity for Dectin-1 receptors ( D'Souza et al, 2022 ), giving an advantage in delivering anti-TB therapeutics and AICs directly to macrophages, enhancing drug payload on targeted cells while decreasing immunotoxicity. Furthermore, the study demonstrated that the produced nanosystem was non-toxic, necessitating future research as a host-directed treatment therapy for Mtb intracellular elimination ( D'Souza et al, 2022 ).…”

“…In these two separate studies ( Dube et al, 2014 , D'Souza et al, 2022 ), the authors' designed drug delivery systems proposed to address the hard-to-treat infectious disease (TB) using NPs modified with ligands that can concurrently modulate the cellular immune response and deliver a drug. Curdlan and 1,3-β-glucan modified PLGA NPs were designed, respectively, following a well-established modified emulsion-solvent evaporation technique.…”

Nanosized Drug Delivery Systems to Fight Tuberculosis

“…For instance, the polysaccharide glucan stimulates macrophages to produce pro-inflammatory signals (ROS and reactive nitrogen species), including IL-12 and TNFα, which are known to be crucial in the control of Mtb [ 154 , 155 ]. More recently, it was shown that curdlan-loaded PLGA NPs with sizes between 330 nm and 453 nm significantly upregulated the pro-inflammatory cytokine TNF-α [ 156 ]. As a consequence, the NPs reduced the intracellular Mtb burden over 72 h in infected RAW264.7 macrophages.…”