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[Preparation and in vitro evaluation of tetrandrine-loaded composite microspheres embedded with PLGA nanoparticles].

In this paper, we prepared a type of composite microspheres embedded with poly (lactic-co-glycolic acid) (PLGA) nanoparticles for efficient inhalation delivery of tetrandrine (Tet), which is a traditional Chinese medicine for anticancer, and studied its morphology, drug release profile, cytotoxicity and cellular uptake behavior. PLGA nanoparticles loading tetrandrine were prepared by emulsion solvent diffusion method, and composite microspheres were prepared by spray drying method with mannitol as matrix due to its osmotic effect. Scanning electronic microscopy, dynamic light scattering laser particle analyzer and confocal microscopy were applied to characterize the morphology and size of the microspheres. The drug loading rate, drug encapsulation efficiency and drug release properties were explored by RP-HPLC. The cytotoxicity in A549 cells between crude drug of Tet and Tet-loaded microspheres were compared by MTT assay. The cellular uptake behavior of microspheres in A549 cells was investigated using confocal laser scanning microscopy. The resultant microspheres were composed of 189 nm PLGA nanoparticles exhibited sizes ranging from 1 to 3 μm, with the highest deposition efficiency. The microspheres can easily be dissolved in a mimic lung environment and release redispersible PLGA nanoparticles. Compared with crude drug of Tet, Tet-loaded microspheres showed a certain sustained release property and higher cytotoxicity effect to A549 cells. The cellular uptake experiment demonstrated a higher excellent penetration ability of cells to nanoparticles and time-dependent uptake process. This study provides a basis for developing new inhalation therapies for lung cancer.