Preparation And Lung-targeting Evaluation Of PLGA Microspheres Loaded With Anticancer Yuanhuacine

Yuanhuacine is daphne diterpene ortho-ester extracted from a traditional Chinesemedicine Daphne genkwa Sieb. et Zucc., which demonstrated potent cytotoxic activity invitro, against particularly for lung tumor cell A549(IC₅₀ 0.15μM), and is a new type of DNAtopoisomerase I inhibitors. The purpose of this research was to develop poly(dl-lactide-co-glycolide) (PLGA 50:50 0.15dl/g) microspheres loaded with yuanhuacine forpassively targeting lung cancer.Dexamethasone was chosen as model drug for the extremely small content ofyuanhuacine in Daphne genkwa and its complicated extraction technic. The orthogonal testwas also used to optimize the preparation condition of the dexamethasone microspheres. Theyuanhuacine microspheres prepared on the optimized condition were spherical with 86.3ï¼…distributed in range from 5 to 20μm and the average size was 9.0μm. The in vitro releasemechanism of yuanhuacine from the microspheres was diffusion controlled and a square rootof time relationship. The photochromic spiropyran labeled fluorescent PLGA microsphereswere firstly used to investigate the in vivo distribution characteristics through intravenousinjection into mice or rabbit. The results indicated that the maximum accumulation in lungwas observed at 6h after intravenous injection. Histological sections from different organsindicated that most particles between 5-20μm were localized in the lung and the biologicalvariety showed no effect on targeting characteristics. The particle size was the main factoraffecting the lung targeting efficiency. The 5-20μm group demonstrated well lung targetingcharacteristic, but＜5μm group and＞20μm groups didn't. The fluorescent microscopyevaluation method showed similar results as that of HPLC-UV method on evaluation of thelung targeting efficiency, 79.3ï¼…and 81.8ï¼…respectively. This method is easy to conduct,visualized and accurate. It could supply other researchers and studies a novel channel toevaluate the targeting efficiency.