Preparation Of Rifapentine Loaded Poly (Lactic-co-glycolic Acid) Nanoparticles And Characteristics Of Drug Release In Vitro

Objective:To solve effectively the limitation of systemic administration of traditional drugs,a new anti-tuberculosis nano-delivery system was developed and its prescription and preparation process were optimized.The behavior of nano-particle drug release in vitro was initially explored.Method:Using Rifapentine（RPT）as a drug model,poly（lactic-co-glycolic acid）（PLGA）as a carrier,and using premix membrane emulsification to prepare RPT/PLGA nanoparticles.The single-factor experiment was used to investigate the effects of emulsifier concentration,PLGA concentration,oil phase/water phase volume ratio（O/W）,tansmembrane pressure,number of extrusions,premix speed and time,using particle size,PDI,drug loading rate,and encapsulation efficiency as evaluation indicators.The formulation and process were optimized by L₁₆（3⁵）orthogonal experiment based the single-factor experiment.The results were comprehensively analyzed by the TOPSIS method.Then verify the optimal prescription process and investigate the drug release behavior of drug-loaded nanoparticles in vitro.Results:The emulsifier concentration,PLGA concentration,oil phase/water phase volume ratio,and tansmembrane pressure were the main factors affecting the preparation.The drug-loaded nanoparticles were prepared by the optimal prescription process,the mean size was（428±11.4）nm,PDI was about 0.186±0.036,the zeta potential was（-17.56±3.15）mV,and the encapsulation efficiency was（76.89±2.6）%,The drug loading rate was（10.89±1.2）%.Observed with a transmission electron microscope,the spherical shape was uniformly distributed,and the dispersion was good.The cumulative percentage of the drug released was 78.81%during 72 hours in vitro release behavior,while the RPT was released in more than 90%within 5h.Conclusion:RPT/PLGA nanoparticles with uniform roundness,good encapsulation and sustained-release properties can be easily and quickly prepared by premix membrane emulsification,which will provide theoretical basis for reducing the dose and frequency of administration,reducing the systemic toxicity of drugs and improving patient compliance in future clinical practice.It also provides the experimental basis for the later in vivo research.