Tuberculosis (TB) remains a significant global health challenge, necessitating innovative approaches for effective treatment. Conventional TB therapy encounters several limitations, including extended treatment duration, drug resistance, patient noncompliance, poor bioavailability, and suboptimal targeting. Advanced drug delivery strategies have emerged as a promising approach to address these challenges. They have the potential to enhance therapeutic outcomes and improve TB patient compliance by providing benefits such as multiple drug encapsulation, sustained release, targeted delivery, reduced dosing frequency, and minimal side effects. This review examines the current landscape of drug delivery strategies for effective TB management, specifically highlighting lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, emulsion-based systems, carbon nanotubes, graphene, and hydrogels as promising approaches. Furthermore, emerging therapeutic strategies like targeted therapy, long-acting therapeutics, extrapulmonary therapy, phototherapy, and immunotherapy are emphasized. The review also discusses the future trajectory and challenges of developing drug delivery systems for TB. In conclusion, nanomedicine has made substantial progress in addressing the challenges posed by conventional TB drugs. Moreover, by harnessing the unique targeting abilities, extended duration of action, and specificity of advanced therapeutics, innovative solutions are offered that have the potential to revolutionize TB therapy, thereby enhancing treatment outcomes and patient compliance. 

Advanced drug delivery and therapeutic strategies for tuberculosis treatment

We reveal for the first time by experiments that within a narrow parameter regime, two cavitation bubbles with identical energy generated in antiphase develop a supersonic jet. High-resolution numerical simulation shows a mechanism for jet amplification based on toroidal shock wave and bubble necking interaction. The microjet reaches velocities in excess of 1000  m s^{-1}. We demonstrate that potential flow theory established for Worthington jets accurately predicts the evolution of the bubble gas-liquid interfaces unifying compressible and incompressible jet amplification.

Amplification of Supersonic Microjets by Resonant Inertial Cavitation-Bubble Pair.

Infectious diseases, such as Mycobacterium tuberculosis (Mtb)-caused tuberculosis (TB), remain a global threat exacerbated by increasing drug resistance. Host-directed therapy (HDT) is a promising strategy for infection treatment through targeting host immunity. However, the limited understanding of the function and regulatory mechanism of host factors involved in immune defense against infections has impeded HDT development. Here, we identify the ubiquitin ligase (E3) TRIM27 (tripartite motif-containing 27) as a host protective factor against Mtb by enhancing host macroautophagy/autophagy flux in an E3 ligase activity-independent manner. Mechanistically, upon Mtb infection, nuclear-localized TRIM27 increases and functions as a transcription activator of TFEB (transcription factor EB). Specifically, TRIM27 binds to the TFEB promoter and the TFEB transcription factor CREB1 (cAMP responsive element binding protein 1), thus enhancing CREB1-TFEB promoter binding affinity and promoting CREB1 transcription activity toward TFEB, eventually inducing autophagy-related gene expression as well as autophagy flux activation to clear the pathogen. Furthermore, TFEB activator 1 can rescue TRIM27 deficiency-caused decreased autophagy-related gene transcription and attenuated autophagy flux, and accordingly suppressed the intracellular survival of Mtb in cell and mouse models. Taken together, our data reveal that TRIM27 is a host defense factor against Mtb, and the TRIM27-CREB1-TFEB axis is a potential HDT-based TB target that can enhance host autophagy flux.

TRIM27 elicits protective immunity against tuberculosis by activating TFEB-mediated autophagy flux.

Jetting of a near-wall cavitation bubble induced by another tandem bubble

A high-fidelity multiphase flow computational model is utilized to investigate the interaction mechanism between anti-phase tandem bubbles and tissue materials in a free-field environment. The formation of liquid jets generated by tandem bubble coupling and its effects on tissue deformation are analyzed. Parametric studies are conducted to explore the impacts of bubble–bubble distance (γbb), bubble size ratio (Sbb), and bubble–tissue distance (γtb). The results indicate that the regime of tissue penetration varies under different γbb. For small γbb, the tissue deformation is mainly attributed to the stretching of upper bubbles and liquid jets; whereas for large γbb, tissue deformation is primarily induced by the jets themselves; and for moderate γbb values, it is caused by a combined effect involving both jets and the evolution of toroidal bubbles. Comparative analysis shows the significant impact of varying Sbb on bubble coupling dynamics, with larger Sbb values correlating with more potent tissue penetration. Furthermore, the study also reveals that, beyond γtb exceeding 3, penetration ceases to manifest, advocating for the maintenance of γtb below 1.4 for practical applications.

Dynamics of tandem bubble interaction near tissue

This paper is associated with a video winner of a 2021 American Physical Society's Division of Fluid Dynamics (DFD) Milton van Dyke Award for work presented at the DFD Gallery of Fluid Motion. The original video is available online at the Gallery of Fluid Motion, https://doi.org/10.1103/APS.DFD.2021.GFM.V0038. 

Flow focusing from interacting cavitation bubbles

Tweaking host immune responses for novel therapeutic approaches against Mycobacterium tuberculosis.

The persistence of Mycobacterium tuberculosis makes it difficult to eradicate the associated infection from the host. The flexible nature of mycobacteria and their ability to adapt to adverse host conditions give rise to different drug-tolerant phenotypes. Granuloma formation restricts nutrient supply, limits oxygen availability and exposes bacteria to a low pH environment, resulting in non-replicating bacteria. These non-replicating mycobacteria, which need high doses and long exposure to anti-tubercular drugs, are the root cause of lengthy chemotherapy. Novel strategies, which are effective against non-replicating mycobacteria, need to be adopted to shorten tuberculosis treatment. This not only will reduce the treatment time but also will help prevent the emergence of multi-drug-resistant strains of mycobacteria.

Unravelling the flexibility of Mycobacterium tuberculosis: an escape way for the bacilli.

Role of transcription termination factor Rho in anti-tuberculosis drug discovery.

The awe-inspiring multi-generational, transoceanic migration circuit of dragonfly species, Pantala flavescens stretches from India to Africa. Understanding the collective role of wind, precipitation, fuel, breeding, and life cycle driving the migration remains elusive. We identify the transoceanic migration route from years 2002 to 2007 by imposing an energetics-based time-constraint on a modified Dijkstra’s path-planning algorithm incorporating active wind compensation. The prevailing winds play a pivotal role; the Somali Jet enables migration across the Indian Ocean from Africa to India, whereas the return requires stopovers at the disappearing islands of the Maldives and Seychelles. The migration timing, identified using monthly-successful trajectories, life cycle, and precipitation data, corroborates sightings. A branched-network hypothesis connects our sighting in Cherrapunji (North-East India), the likely origin, to the known migration circuit.

/pdf/transoceanic-migration-network-of-dragonfly-pantala-18d95zgo.pdf

Transoceanic migration network of dragonfly Pantala flavescens: origin, dispersal and timing

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