Targeted Nasal Route Delivery of Cationic Anti-TB Drug-Loaded Nano-embedded Microparticles for Mycobacterial Elimination in the CNS DOI
Krishna Jadhav,

Agrim Jhilta,

Raghuraj Singh

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Central nervous system tuberculosis (CNS-TB) is a severe and insidious form of extrapulmonary (TB) associated with high mortality rate, often leading to fatal outcomes or debilitating neurological impairments. The therapeutic regimen for CNS-TB follows an approach similar that pulmonary TB but faces significant challenges in effectively reaching the cerebrospinal fluid achieving drug levels brain surrounding fluids. A major obstacle treatment difficulty permeating blood-brain barrier (BBB). nasal route delivery offers promising targeting anti-TB drugs directly infection sites, enabling higher concentrations while bypassing BBB. present study focused on development cationic poly(lactic-co-glycolic) acid (PLGA) nanoparticles (CS-PLGA NPs) loaded (ATDs), namely, isoniazid (INH) rifampicin (RIF). These CS-PLGA NPs were then processed into dynamic microsized nanoembedded microparticles (NEMs) using spray drying. ATD-NEMs formulation demonstrated significantly enhanced permeation across RPMI 2650 septum monolayers compared free ATDs. Intranasal NEM TB-infected mice over four-week period resulted substantial reduction colony-forming units (CFUs) (1.53 ± 0.50 log10 CFU/gram) untreated group (4.45 0.67 CFU/gram). Furthermore, showed improved recovery histopathological analysis, consistent CFU reduction. Preclinical data support feasibility intranasally administering NEMs formulation, demonstrating efficacy potential address inflammation murine model.

Language: Английский

Host-Directed Therapy with Inhalable Lovastatin Microspheres for Matrix Metalloproteinase Inhibition in Tuberculosis DOI

Agrim Jhilta,

Krishna Jadhav, Rahul Sharma

et al.

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Tuberculosis (TB) triggers a robust immune response, which leads to significant destruction of the lung tissue at site infection, aiding in transmission Mycobacterium tuberculosis (Mtb) hosts. The excessive inflammatory response contributes heavily extracellular matrix (ECM) damage, is linked high mortality rates among TB patients. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, are pivotal breakdown ECM, worsening destruction. In context host-directed therapy (HDT), strategy aimed modulating rather than directly targeting pathogen, we evaluated potential lovastatin (LOV). LOV has shown promise reducing MMP activity inflammation, could alleviate immune-mediated pathology TB. However, its clinical use been limited due poor solubility biocompatibility, therapeutic efficacy. To overcome these limitations, designed inhalable gelatin microspheres (GA-MS) loaded with using spray-drying technology. This approach improved allowed for controlled release drug. resulting LOV-loaded (LOV/GA-MS) had an optimal particle size 2.395 ± 0.67 μm, facilitating macrophage uptake their aerodynamic properties. vitro studies Mtb-infected macrophages, LOV/GA-MS effectively suppressed expression reduced levels pro-inflammatory cytokines concentration 20 μg/mL, demonstrating substantial anti-inflammatory potential. Moreover, showed synergistic effect when combined standard anti-TB drugs, enhancing overall efficacy experiments. findings suggest that represent promising adjunctive By host's key mediators such as MMPs, this mitigate improve outcomes, provide more holistic treatment option

Language: Английский

Citations

0
Advances in spray drying technology for anti-tubercular formulation development: A comprehensive review DOI
Eknath Kole, Krishna Jadhav, Yogesh A. Sonar

et al.

Drying Technology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 37

Published: Jan. 27, 2025

Language: Английский

Citations

0
Polymer optical waveguide recoverable evanescent field nitroaromatics sensor based on D-π-A chromophore DOI
Jinkai Wang,

Xiangzhuo Han,

Yingzhe Wang

et al.

Analytical and Bioanalytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

0
Peptide–Drug Conjugates as Next-Generation Therapeutics: Exploring the Potential and Clinical Progress DOI Creative Commons
Krishna Jadhav, Ashwin Abhang, Eknath Kole

et al.

Bioengineering, Journal Year: 2025, Volume and Issue: 12(5), P. 481 - 481

Published: April 30, 2025

Peptide–drug conjugates (PDCs) have emerged as a next-generation therapeutic platform, combining the target specificity of peptides with pharmacological potency small-molecule drugs. As an evolution beyond antibody–drug (ADCs), PDCs offer distinct advantages, including enhanced cellular permeability, improved drug selectivity, and versatile design flexibility. This review provides comprehensive analysis fundamental components PDCs, homing peptide selection, linker engineering, payload optimization, alongside strategies to address their inherent challenges, such stability, bioactivity, clinical translation barriers. Therapeutic applications span oncology, infectious diseases, metabolic disorders, emerging areas like COVID-19, several advancing in trials achieving regulatory milestones. Innovations, bicyclic peptides, supramolecular architectures, novel technologies, are explored promising avenues enhance PDC design. Additionally, this examines trajectory emphasizing potential highlighting ongoing that exemplify efficacy. By addressing limitations leveraging advancements, hold immense promise targeted therapeutics capable complex disease states driving progress precision medicine.

Language: Английский

Citations

0
Targeted Nasal Route Delivery of Cationic Anti-TB Drug-Loaded Nano-embedded Microparticles for Mycobacterial Elimination in the CNS DOI
Krishna Jadhav,

Agrim Jhilta,

Raghuraj Singh

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Central nervous system tuberculosis (CNS-TB) is a severe and insidious form of extrapulmonary (TB) associated with high mortality rate, often leading to fatal outcomes or debilitating neurological impairments. The therapeutic regimen for CNS-TB follows an approach similar that pulmonary TB but faces significant challenges in effectively reaching the cerebrospinal fluid achieving drug levels brain surrounding fluids. A major obstacle treatment difficulty permeating blood-brain barrier (BBB). nasal route delivery offers promising targeting anti-TB drugs directly infection sites, enabling higher concentrations while bypassing BBB. present study focused on development cationic poly(lactic-co-glycolic) acid (PLGA) nanoparticles (CS-PLGA NPs) loaded (ATDs), namely, isoniazid (INH) rifampicin (RIF). These CS-PLGA NPs were then processed into dynamic microsized nanoembedded microparticles (NEMs) using spray drying. ATD-NEMs formulation demonstrated significantly enhanced permeation across RPMI 2650 septum monolayers compared free ATDs. Intranasal NEM TB-infected mice over four-week period resulted substantial reduction colony-forming units (CFUs) (1.53 ± 0.50 log10 CFU/gram) untreated group (4.45 0.67 CFU/gram). Furthermore, showed improved recovery histopathological analysis, consistent CFU reduction. Preclinical data support feasibility intranasally administering NEMs formulation, demonstrating efficacy potential address inflammation murine model.

Language: Английский

Citations

0