Abstract
Objective:The objective of the present work was to formulate Prothionamide (PTH) nanoparticles using Poly lactic co-glycolic acid (PLGA), optimized by Box-Behnken Design and further modification to dry powder inhaler followed byin-vivostudy.Methods:Poly-lactic co-gycolic acid (PLGA), a biodegradable polymer was used to coat Prothionamide by solvent evaporation technique. Formulation was optimized using Box-Behnken Design. Response surface curve and desirability factors helped in the selection of optimum formulation of PTH nanoparticles. Dry powder inhaler was prepared by adding inhalable grade lactose to optimize PTH nanoparticles. Mass median aerodynamic diameter (MMAD) was carried out using Andersen Cascade Impactor (ACI) to demonstrate its suitability in the pulmonary administration.In-vitrodrug release of dry powder inhaler was carried out in simulated lungs fluid. Correlationin-vitrotoin-vivowas established after performing animal experiment.Results:FTIR study reveals no chemical interaction between PTH, lactose and PLGA as the principle peaks was retained with same intensity in the physical mixture. Scanning electron microscope showed the spherical shape and aerodynamic particle size was found to be 1.69µm. Drug release study showed initial burst release followed by zero order release.In-vivomodel confirmed the presence of PTH after 24h. Aerodynamic particle size and the release profile revealed the suitability of PTH loaded nanoparticles containing dry powder inhaler for the pulmonary administration.Conclusion:Prepared DPI containing PTH nanoparticles can improve in the management of tuberculosis by increasing PTH residency in the lungs tissue for prolong period of time.
Highlights
Tuberculosis (TB) is a common and often deadly infectious disease caused mostly due to Mycobacterium tuberculosis
FTIR study reveals no chemical interaction between PTH, lactose and PLGA as the principle peaks was retained with same intensity in the physical mixture
Aerodynamic particle size and the release profile revealed the suitability of PTH loaded nanoparticles containing dry powder inhaler for the pulmonary administration
Summary
Tuberculosis (TB) is a common and often deadly infectious disease caused mostly due to Mycobacterium tuberculosis. Over the past couple of decades, the field of drug delivery has been revolutionized with the introduction of nanoparticles, wherein these particles act as excellent carriers for drugs to target cells or tissues [5]. Biodegradable polymers such as poly(D,L-lactic acid) (PLA), poly D,L-lactic-co-glycolic acid (PLGA), and poly-ε-caprolactone (PCL) and their copolymers di-blocked or multi blocked with poly ethylene glycol (PEG) have been generally used to form polymeric nanoparticles (NPs) to encapsulate a variety of therapeutic compounds [6]. Optimized nanoparticles further modified into dry powder inhaler to make suitable for pulmonary administration and targeting PTH to lungs
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