Fabrication and optimization of freeze-dried isoniazid-loaded poly-<i>ε</i>-caprolactone nanoparticles

Background Microfluidic nanoprecipitation followed by freeze-drying would yield uniformly sized, stable nanoparticles by preserving their physicochemical property without compromising therapeutic performance. The isoniazid (INH)-loaded poly- ε -caprolactone (PCL) nanoparticles could be developed using a microfluidic technique for the management of tuberculosis. Experimental approach The INH-loaded nanoparticles were fabricated via a microreactor-assisted nanoprecipitation method and optimization using a design of experiments factorial design approach. The resulting INH-PCL nanoformulation was characterized for particle size, polydispersity index (PDI), zeta potential (surface charge), Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction analysis and field emission scanning electron microscope. Key results The optimized nanoparticles exhibited an average particle size (248.4 ± 5.372 nm) and high encapsulation efficiency (82.26 ± 4.36 %). Thermal and spectroscopic analyses confirmed the absence of drug-polymer interactions, ensuring formulation integrity; stability studies under accelerated conditions demonstrated negligible changes in particle size, PDI, and zeta potential over the period of 6 months, indicating robust colloidal stability. A scanning electron microscopy study revealed rod-shaped nanoparticles with smooth surfaces. Lyophilization (freeze-drying) enhanced long-term stability, yielding a readily re-dispersible powder (reconstitution index ~1.066). Following diffusion-controlled kinetics, in vitro drug release studies in phosphate buffer saline (pH 7.4) showed sustained drug release (92.45 % cumulative release over 48 h). Conclusion Our results confirm that the INH-loaded PCL nanoformulation combines excellent stability, high drug-loading capacity, and sustained release, key attributes of effective tuberculosis therapy.