Poloxamer-Based Thermosensitive Nanoparticle in situ Gel for Sustained Pulmonary Anti-Tubercular Drug Delivery

Background

Tuberculosis treatment requires prolonged multidrug therapy, often associated with poor patient compliance and systemic side effects. The present study aimed to develop and optimize a Poloxamer 407-based thermosensitive nanoparticle-loaded in situ gel system for sustained pulmonary delivery of first-line anti-tubercular drugs.

Materials and Methods

Drug-loaded sodium alginate nanoparticles containing isoniazid, rifampicin, moxifloxacin HCl, and pyrazinamide were prepared by emulsification and incorporated into thermosensitive in situ gels using varying concentrations of Poloxamer 407 (18-21% w/w). The formulations were evaluated for gelation temperature, pH, viscosity, drug entrapment efficiency, in vitro drug release, and in vivo pharmacokinetic performance.

Results

The optimized formulations containing 20% Poloxamer 407 exhibited suitable gelation temperatures (30.79-32.89ºC), acceptable pH (5.22-5.55), and viscosity (2260 ± 2.08 to 3144 ± 4.04 cps). High drug entrapment efficiencies (>98%) and sustained drug release (93-99% over 12 hr) were achieved. In vivo pharmacokinetic studies demonstrated prolonged systemic exposure, increased half-life, and improved bioavailability compared with conventional oral drug solutions.

Conclusion

The developed nanoparticle-loaded thermosensitive in situ gel system demonstrated effective sustained pulmonary delivery and enhanced pharmacokinetic performance of anti-tubercular drugs. This platform may improve therapeutic efficacy, reduce dosing frequency, and enhance patient compliance in tuberculosis management.