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Mannosamine-Engineered Nanoparticles for Precision Rifapentine Delivery to Macrophages: Advancing Targeted Therapy Against Mycobacterium Tuberculosis
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Mannosamine-Engineered Nanoparticles for Precision Rifapentine Delivery to Macrophages: Advancing Targeted Therapy Against Mycobacterium Tuberculosis
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Journal Article
Mannosamine-Engineered Nanoparticles for Precision Rifapentine Delivery to Macrophages: Advancing Targeted Therapy Against Mycobacterium Tuberculosis
2025
Overview
Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains one of the leading causes of death among infectious diseases. Enhancing the ability of anti-tuberculosis drugs to eradicate Mycobacterium tuberculosis within host cells remains a significant challenge.
A mannosamine-modified nanoparticle delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) copolymers to enhance the targeted delivery of rifapentine (RPT) to macrophages. D-mannosamine was conjugated to PLGA-polyethylene glycol (PLGA-PEG) copolymers through EDC/NHS coupling chemistry, and the resultant RPT-MAN-PLGA-PEG nanoparticles (NPs) were prepared through a combination of phacoemulsification and solvent evaporation methods. The physicochemical properties, toxicity, in vitro drug release profiles, stability, cellular uptake, and anti-TB efficacy of the NPs were systematically evaluated.
The RPT-MAN-PLGA-PEG NPs had a mean particle size of 108.2 ± 7.2 nm, with encapsulation efficiency and drug loading rates of 81.2 ± 6.3% and 13.7 ± 0.7%, respectively. RPT release from the NPs was sustained for over 60 hours. Notably, the phagocytic uptake of the MAN-PLGA NPs by macrophages was significantly higher compared to PLGA-PEG NPs. Both NPs improved pharmacokinetic parameters without inducing significant organ toxicity. The minimum inhibitory concentration for the NPs was 0.047 μg/mL, compared to 0.2 μg/mL for free RPT.
The engineered RPT-MAN-PLGA-PEG NPs effectively enhanced macrophage uptake in vitro and facilitated the intracellular clearance of Mtb. This nanoparticle-based delivery system offers a promising approach for improving the precision of anti-TB therapy, extending drug release, optimizing pharmacokinetic profiles, augmenting antimicrobial efficacy, and mitigating drug-related toxicities.
Publisher
Dove Medical Press Limited,Taylor & Francis Ltd,Dove Press,Dove,Dove Medical Press
Subject
/ Animals
/ Antitubercular Agents - administration & dosage
/ Antitubercular Agents - chemistry
/ Antitubercular Agents - pharmacology
/ BCG
/ Dose-Response Relationship, Drug
/ Ethylenediaminetetraacetic acid
/ Humans
/ Ligands
/ Mice
/ Minimum inhibitory concentration
/ Mycobacterium tuberculosis - drug effects
/ Polyethylene Glycols - chemistry
/ Polylactic Acid-Polyglycolic Acid Copolymer - chemistry
/ Polymers
/ Polyols
/ Rifampin - administration & dosage
/ Rifampin - analogs & derivatives
/ Structure-Activity Relationship
/ Toxicity
