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Host-Directed Therapy with Inhalable Lovastatin Microspheres for Matrix Metalloproteinase Inhibition in Tuberculosis
Agrim Jhilta1, Krishna Jadhav1, Rahul Sharma2
1Institute of Nano Science and Technology (INST), Sector-81, Mohali, Punjab 140306, India.
ACS Applied Bio Materials
|January 20, 2025
Summary
Inhalable lovastatin microspheres effectively reduced lung inflammation and tissue damage in tuberculosis models. This host-directed therapy shows promise as an adjunctive treatment for tuberculosis (TB).
Area of Science:
- Immunology
- Pharmacology
- Biomaterials
Background:
- Tuberculosis (TB) causes lung tissue destruction via excessive inflammation and extracellular matrix (ECM) degradation, mediated by matrix metalloproteinases (MMPs).
- Host-directed therapy (HDT) aims to modulate the immune response to mitigate TB pathology.
- Lovastatin (LOV) has anti-inflammatory properties but suffers from poor solubility and biocompatibility, limiting its therapeutic use.
Purpose of the Study:
- To develop inhalable lovastatin-loaded gelatin microspheres (LOV/GA-MS) for improved TB treatment.
- To evaluate the efficacy of LOV/GA-MS in suppressing inflammation and ECM damage in Mtb-infected macrophages.
- To assess the synergistic potential of LOV/GA-MS with standard anti-TB drugs.
Main Methods:
- Spray-drying technology was used to create inhalable gelatin microspheres (GA-MS) loaded with lovastatin (LOV).
- Particle size and aerodynamic properties of LOV/GA-MS were characterized.
- In vitro studies were conducted using Mycobacterium tuberculosis (Mtb)-infected macrophages to assess anti-inflammatory effects and drug synergy.
Main Results:
- LOV/GA-MS exhibited an optimal particle size (2.395 ± 0.67 μm) for macrophage uptake.
- LOV/GA-MS significantly suppressed MMP expression and pro-inflammatory cytokines in Mtb-infected macrophages.
- A synergistic therapeutic effect was observed when LOV/GA-MS were combined with standard anti-TB drugs in vitro.
Conclusions:
- Inhalable LOV/GA-MS represent a promising strategy for host-directed therapy in TB.
- This formulation effectively modulates the immune response by targeting MMPs and reducing inflammation.
- LOV/GA-MS offer a potential approach to mitigate lung tissue damage and enhance TB treatment outcomes.
Keywords:
host-directed therapyinhalationlovastatinlung inflammationmatrix metalloproteinasemicrospherestuberculosisMore Related Videos
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