Subcutaneous nanoparticle-based antitubercular chemotherapy in an experimental model

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Tuberculosis (TB) treatment requires long-term medication, leading to challenges with patient compliance and drug resistance.
• Current TB drug delivery methods often result in suboptimal bioavailability and frequent dosing.

Purpose of the Study:

• To develop and evaluate Poly (DL-lactide-co-glycolide) (PLG) nanoparticles for sustained delivery of key anti-TB drugs.
• To assess the pharmacokinetic and therapeutic efficacy of these drug-loaded nanoparticles in a mouse model.

Main Methods:

• Preparation of PLG nanoparticles encapsulating rifampicin, isoniazid, and pyrazinamide using the multiple emulsion technique.
• Subcutaneous administration of nanoparticles to mice for pharmacokinetic analysis and chemotherapeutic evaluation in Mycobacterium tuberculosis-infected models.

Main Results:

• Sustained therapeutic drug concentrations were observed in plasma for 32 days and in lungs/spleen for 36 days post-single dose.
• Drug-loaded PLG nanoparticles demonstrated a significant increase in mean residence time and absolute bioavailability compared to unencapsulated drugs.
• Complete eradication of detectable Mycobacterium tuberculosis in lungs and spleen was achieved, outperforming daily free drug administration.

Conclusions:

• Injectable PLG nanoparticles offer a promising platform for sustained delivery of anti-TB drugs.
• This approach enhances drug bioavailability and reduces dosing frequency, potentially improving tuberculosis management and patient adherence.