Study On Rifapentine-linezolid-loaded PLGA Microspheres For Lung Targeting Drug Delivery

Objective:In this study,we aimed to design controlled-release microspheres of rifapentine and linezolid using poly(lactic-co-glycolic acid)(PLGA)for the main material.The drug controlled-release system was for the treatment of tuberculosis(TB)for solving the issues of poor drug delivery and short duration maintained at effective drug concentration during bronchoscopic interventional therapy.Methods:Firstly,we established the high-performance liquid chromatography(HPLC)detect method of rifapentine and linezolid.Secondly,We fabricated rifapentine-linezolid-loaded PLGA microspheres(RLPMs)using the oil-in-water emulsion solvent evaporation method.The best preparation method was confirmed by morphology,particle size,drug loading and encapsulation efficiency of RLPMs.Finally,we assessed their in vitro release,the bronchial mucosal retention characteristics as well as the pathological observation of bronchus and lung.Results:The microspheres are spherical in shape with a circular concave on the surface.The particle size of RLPMs was 27.38±1.28μm.The drug loading of rifapentine and linezolid was 18.51±0.26% and 8.42±0.24%,respectively,while the encapsulation efficiencies were 55.53±0.78% and 16.87±0.47%,respectively(n=3).During the burst release phase of the in vitro release test,21.37 ± 0.68% rifapentine was released in 3 days and 43.56 ± 2.54% linezolid was released in 1 day.Then,both the drugs entered the sustained release phase.Finally,the cumulative percentage release of rifapentine and linezolid in 14 days was 27.61±1.52% and 51.01±3.31%,respectively(n=3).In vitro release,the bronchial mucosal retention characteristics as well as the pathological observation of bronchus and lung of miscrospheres revealed that the controlled-release microspheres are safe and reliable and could slowly release the drugs and retain them on the surface of bronchial mucosa of canines for 20 days.Conclusion:These results indicated that the fabricated microspheres are safe and reliable,exhibited a significant sustained release effect and could effectively retain the drugs on the surface of bronchial mucosa.