Pulmonary Delivery of Linezolid Nanoparticles for Treatment of Tuberculosis: Design, Development, and Optimization
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ORIGINAL ARTICLE
Pulmonary Delivery of Linezolid Nanoparticles for Treatment of Tuberculosis: Design, Development, and Optimization Sunny Shah 1
&
Hiren Maheshwari 1 & Moinuddin Soniwala 1 & Jayant Chavda 1
Accepted: 28 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose The present study was aimed to develop and optimize linezolid loaded chitosan nanoparticles for pulmonary delivery. The objective was to achieve the mean particle size of nanoparticles less than 300 nm and the mass median aerodynamic diameter (MMAD) less than 5 μm and sustain the drug release up to 24 h. Methods Linezolid nanoparticles were prepared by ionic gelation technique employing chitosan and sodium tripolyphosphate (STPP). A 32 full factorial design and desirability function were sequentially used to quantify the effect of independent variables on dependent variables and optimize the formulation. Results The preliminary studies suggested that the concentration of chitosan and concentration of STPP had an appreciable effect on mean particle size and percentage entrapment efficiency and hence were selected as independent variables in a factorial design. Statistical analysis of 32 full factorial design revealed that each independent variable had a significant effect (p < 0.05) on the dependent variables. Conclusion The optimized formulation with desirability value 0.8193 showed a mean particle size of 91.40 nm, MMAD of 3.19 μm, and sustained the drug release up to 24 h in simulated lung fluid. However, further in vivo studies are required to design suitable dosage regimen and establish the fate of nanoparticles for safe and efficacious delivery of the drug. Keywords Linezolid . Chitosan – sodium tripolyphosphate nanoparticles . Pulmonary delivery . Minimum inhibitory concentration . Tuberculosis
Introduction Pulmonary tuberculosis (TB), one of the most contagious diseases prevalent in India and the world, is in the top 10 causes of death and the leading cause of a single infectious agent (above HIV/AIDS) [1]. In India itself, the number of such cases grew from 1.2 million to 2.0 million from 2013 to 2018. As of September 2019, the World Health Organization (WHO) report on the global tuberculosis burden suggests that India alone accounts for more than 27% of the global tuberculosis burden. Further, 135,000 patients have progressed from tuberculosis to multidrug-resistant Mycobacterium tuberculosis (MDR-TB) [2]. The conventional drug delivery system under the Directly Observed * Sunny Shah [email protected] 1
B. K. Mody Government Pharmacy College, Nr. Aji Dam, Rajkot, India
Treatment Short Course (DOTS) has reaped great benefits; however, it requires a long-term regimen to achieve sterility of the lungs [3, 4] which results in poor patient compliance. WHO has revised its guidelines for the treatment of MDRTB which now includes linezolid along with later-generation fluoroquinolones such as levofloxacin and other agents like bedaquiline for effective treatment of MDR-TB. Linezolid (Fig. 1)
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