Exploring Polymeric Nano-Particles as Targeted Pulmonary Delivery of Rifampicin, Ethambutol and Ofloxacin against Inh-Resistant Tuberculosis

Abstract

Present research focus on novel combination of Rifampicin, Ofloxacin and Ethambutol loaded polymeric nanoparticles for the effective eradication of isoniazid resistant species of Tuberculosis. The nanoparticles containing Rifampicin, Ethambutol and Ofloxacin were prepared by spray drying technique using biodegradable polymer PLGA through critical process as well as polymer attributes which were identified and screened using Plackett-Burman screening design. Partial least square equation generated using Minitab Software for processing parameters as flow rate- 5ml/min, inlet temperature- 60˚C, aspirator capacity- 50, ultrasonication time 40 min, ultrasonic amplitude % 60, and product parameters like drug: polymer ratio 2:1, aerosil concentration 1%, Solvent (DCM: Ethanol) ratio 75:25 on critical responses i.e. particles size, encapsulation efficiency, and product yield. Diffusion study revealed that optimum formulation containing 2:1 drug to polymer ratio was able to sustain the release of drugs up to 12hrs. Particles Size was found to be less than 100 nm with uniform spherical shape and good agreement using TEM analysis. The three drug combination showed significantly synergism (p 0.007) for isoniazid susceptible species during in-vitro antimicrobial assay prove better efficacy. Overall study explored potential use of polymeric particles as targeted delivery system for drug susceptible and isoniazid resistant tuberculosis treatment.