Preparation and in vitro evaluation of exenatide-loaded poly （lactic-co-glycolic acid） nanoparticles

Abstract:

Objective：To prepare exenatide-loaded poly（lactic-co-glycolic acid）（PLGA） nanoparticles，and to evaluate its in vitro ef－fect and characteristics. Methods：The orthogonal experimental design was used to screen out the optimal formulation and process of exenatide-loaded PLGA nanoparticles，and dynamic light scattering and a transmission electron microscope were used for characteri－zation. In vitro simulation of gastrointestinal fluid and Caco-2 cell model were used to evaluate its stability，cellular uptake，and cellular transport. Results：The optimal formulation and process were obtained by the orthogonal design，i.e.，a volume ratio of internal water phase to oil phase of 1∶5，an ultrasonic power of 200 W，an ultrasonic time of 4 minutes，a concentration of polyvinyl alcohol of 2%，and a volume ratio of primary emulsion to external water phase of 1∶20. The nanoparticles obtained had a diameter of 116.2 nm and the transmission electron microscope showed that PLGA nanoparticles had a sphere-like shape with a regular surface. The in vit－ro study demonstrated that PLGA nanoparticles significantly prolonged the release of exenatide in gastrointestinal fluid and improved its stability（P<0.05），and 50% of exenatide was retained after 4-hour culture in simulated gastric fluid，while 80% was retained after 4-hour culture in simulated intestinal juice. The cell experiment showed that the uptake and transport of PLGA nanoparticles in the experimental group were 7 and 5 times those in the control group（P<0.05）. Conclusion：PLGA nanoparticles may be a potential effi－cient oral drug delivery system for exenatide.